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INFORMATION FOR

Joseph Broderick - Harnessing the Power of Clinical Trial Networks for Stroke - NIH StrokeNet

October 27, 2021
  • 00:00This brings us our next talk,
  • 00:02which will be given by Doctor Rodrick.
  • 00:05I'll hand it over to doctor Karen
  • 00:07Fury from Brown University.
  • 00:09All introduce Dr.
  • 00:11Broderick and she will moderate
  • 00:13this session as well. Great thanks.
  • 00:15Shawty uhm we are very fortunate
  • 00:18to have Joe Broderick with us today
  • 00:21to deliver a keynote address.
  • 00:23Uhm, Joe is currently professor and
  • 00:26director of the University of Cincinnati,
  • 00:30Gardner Neuroscience Institute.
  • 00:32He's been at the University of
  • 00:35Cincinnati since 1987 and was
  • 00:37chair there from 1987 to 2013.
  • 00:40He's been a leader in stroke net
  • 00:43since its inception in 2013 and
  • 00:46is currently the director of the
  • 00:49Clinical Coordinating Center.
  • 00:51Joe is truly a giant.
  • 00:53In the field of stroke,
  • 00:54as all of you know,
  • 00:56he has been either the the P or on
  • 00:59the investigative team of all of the
  • 01:01major trials that have moved forward.
  • 01:04Acute stroke therapies including
  • 01:06TPA and into vascular therapy.
  • 01:08He's been interested in intracerebral
  • 01:11hemorrhage and has really
  • 01:13transformed the field from one of
  • 01:15passive diagnosis of stroke and
  • 01:18intracerebral hemorrhage to a field
  • 01:20where we can actively treat people.
  • 01:23And improve outcomes.
  • 01:24He's also been mentor to many of
  • 01:27today's leaders in stroke and received
  • 01:30awards from the American Heart Association,
  • 01:33including the Clinical Research Prize,
  • 01:36the Feinberg Prize and the
  • 01:39Visionary Research Award.
  • 01:41So it is truly a pleasure to have Joe here.
  • 01:44He's in the unique position of,
  • 01:46you know,
  • 01:47having been part of the evolution of
  • 01:50stroke clinical trials for several decades,
  • 01:53and today.
  • 01:53He's going to share his vision for
  • 01:55the future. I'll hand it over to Joe.
  • 01:57Thank you.
  • 01:58Thanks so much, Karen,
  • 01:59and it's a pleasure to be here.
  • 02:01This is a great conference.
  • 02:02What a great organization.
  • 02:04It's like seeing the best
  • 02:05tips from stroke debt here,
  • 02:07so it's it's been wonderful and I
  • 02:09really appreciate the opportunity
  • 02:11to talk today about harnessing the
  • 02:14power of clinical trial networks
  • 02:16for stroke in the United Stroke net.
  • 02:19So I'm going to.
  • 02:20This is my disclosures.
  • 02:25And there's a lot of advantages of national
  • 02:28clinical trial networks and stroke Ness,
  • 02:30not the only one in the world.
  • 02:32There's a number of other ones
  • 02:34they'll talk about towards the end.
  • 02:36One of the advantages of a network is
  • 02:38that you can combine the mini minds
  • 02:40and ideas across the network to divide
  • 02:43the best important clinical questions
  • 02:45and design trials to address them.
  • 02:47And as I show you,
  • 02:48I think we got a pretty good pipeline, we.
  • 02:50Boy, it's one of the pleasures of
  • 02:52my job as they give works with
  • 02:54so many smart people from so many
  • 02:56places who really had great ideas.
  • 02:59I think one of the biggest reasons
  • 03:00for at trial network so you don't
  • 03:02have to build a new infrastructure
  • 03:04across the country or globally.
  • 03:06Every time you set out to do a new trial,
  • 03:09the infrastructure is always ready to go.
  • 03:12At those sites that are
  • 03:14successful recruiters,
  • 03:15you could have a centralized Institutional
  • 03:18Review Board consistent contract ING.
  • 03:20You can share best practices across
  • 03:22the trials of network which we do.
  • 03:24You can have an experienced central
  • 03:26research pharmacy which helps when
  • 03:27you're preparing a trial for submission,
  • 03:29but also with getting the trial done.
  • 03:31And finally,
  • 03:32finally,
  • 03:33it's a partnership with our government
  • 03:35research funding agencies in Inds
  • 03:37in this instance,
  • 03:38but other countries have funding
  • 03:39agencies well,
  • 03:40which are pivotal for the access
  • 03:42of these networks.
  • 03:46What's our vision? Our vision is
  • 03:47to be a leading platform for stroke
  • 03:49trials in the US and globally.
  • 03:54Just a quick review of the
  • 03:57history we started in 2013.
  • 03:59Actually, the national Data
  • 04:01Management Center was funded in
  • 04:032014 and the regional center soon
  • 04:05after we have 27 regional centers.
  • 04:0824 that are currently funded with
  • 04:10over 500 satellite hospitals.
  • 04:12The National Coordinating Center at
  • 04:14the University of Cincinnati and the
  • 04:16National Data Management Center at the
  • 04:18University Medical University of South
  • 04:20Carolina and this network with the
  • 04:23regional centers is designed to do.
  • 04:25Phase two and phase three stroke trials,
  • 04:28as well as ancillary trials and
  • 04:30biomarker studies that focus
  • 04:31on acute stroke treatment,
  • 04:33prevention and recovery.
  • 04:37This is actually from earlier in
  • 04:38the network fully, I think before
  • 04:40even the second phase of funding,
  • 04:43but it shows that even at that
  • 04:46time 60% of the US population was
  • 04:48in a 65 mile radius from a stroke
  • 04:50that site and I would say now it's
  • 04:53probably higher in the range.
  • 04:54My guess would be in the range of 70%.
  • 04:58This is our organizational infrastructure
  • 05:00and we have the two coordinating
  • 05:02centers and National Institute
  • 05:04neurologic disease and stroke.
  • 05:07And then we have a steering
  • 05:08committee which is represented by the
  • 05:11regional coordinator leaderships,
  • 05:12such as here with Spirit Executive
  • 05:14Committee which has membership
  • 05:16of the coordinating centers,
  • 05:17NIH and also representation from the RCC
  • 05:22and then the Operation Committee which
  • 05:24meets weekly that examines and looks
  • 05:26at all the ongoing trials which also.
  • 05:28Had their own separate Operation committees,
  • 05:31executive committees, etc.
  • 05:33We have two cores imaging core with a
  • 05:35lot of what we do in stroke involves
  • 05:38imaging and then it educational
  • 05:39core which has been extraordinary,
  • 05:42active and successful since its and really
  • 05:44came out of the original educational
  • 05:46cores that were part of spoke Prius,
  • 05:49which is the network which
  • 05:50preceded and I had stroke net.
  • 05:52The working groups which are really
  • 05:55instrumental in looking at the ideas
  • 05:57for the trials and helping work with
  • 05:59the P eyes to get them in great shape
  • 06:02to submit and then also eventually
  • 06:04helping assist with trials as they get
  • 06:06going when there's an issue that comes up.
  • 06:09The advisory committees
  • 06:10are also very important,
  • 06:11such as the Minority Recruitment committee.
  • 06:14Also, there's the end of vascular committees.
  • 06:16There's different committees there that
  • 06:18as we need questions to be addressed,
  • 06:20we can turn to.
  • 06:24But I'm going to show you this,
  • 06:25which gives you an idea of our pipeline.
  • 06:27So this is of July 2021.
  • 06:30And believe it or not,
  • 06:32since beginning we've had 122
  • 06:35trial concepts have been reviewed.
  • 06:37That really is quite a pipeline.
  • 06:3946 acute, 46 prevention,
  • 06:42and 30 recovery Now what happens
  • 06:44is those trial ideas go to Indians
  • 06:47to a committee that says is this
  • 06:49consistent with our mission?
  • 06:51Maybe it should be better someplace else,
  • 06:53or we already funding something
  • 06:54similar to that.
  • 06:55But after that is gone through
  • 06:58there was 46 that were approved to
  • 07:01go forward for the full evaluation
  • 07:04of feasibility and at one time
  • 07:06though six of these were tabled
  • 07:08and I'll talk about them.
  • 07:09Platform concept in just a little bit, but.
  • 07:13The bottom line is at the 42
  • 07:16applications that were submitted,
  • 07:1932 were resubmitted because they needed
  • 07:21to make some changes based upon the review,
  • 07:24but of those 15 so far have
  • 07:26been funded or approved,
  • 07:27which is 36% of those reviewed,
  • 07:30which is quite a high percent
  • 07:31when you look at large grants
  • 07:33submitted for funding to the NIH,
  • 07:35and I think it reflects the
  • 07:37careful work of the working groups
  • 07:40and of the whole network working
  • 07:42to provide the best possible.
  • 07:44Trial ideas and concepts for
  • 07:46consideration of funding.
  • 07:50So this gives you an idea of how quickly
  • 07:53the number of trials has increased.
  • 07:56We had a few back in 2015,
  • 07:59but we're now up to 17 trials that
  • 08:01are currently ongoing in the network,
  • 08:04and that doesn't include some of the
  • 08:07trials that have been completed.
  • 08:09So this is the ongoing stroke net
  • 08:11clinical trials we see up here.
  • 08:12The completed trials.
  • 08:13We see how the ongoing and just to
  • 08:16Orient you the black trials are trials
  • 08:19that were funded independent of stroke
  • 08:21net and the words they went through
  • 08:24a different mechanism for funding.
  • 08:26But stroke net was a great
  • 08:28participant and actually tell rehab
  • 08:30was done all within struggled net,
  • 08:32but the red ones are trials
  • 08:35that came from idea and working
  • 08:37through the initial concept.
  • 08:39All the way to funding and then
  • 08:43either completion or than ongoing
  • 08:45at currently and then the blue one
  • 08:48is a trial that we'll talk about at
  • 08:50the end that's approved by Council,
  • 08:52but it's yet to receive funding,
  • 08:53which hopefully will occur.
  • 08:55Probably the beginning of 2022.
  • 08:59So what have been the outcomes
  • 09:01and impact of stroke trials?
  • 09:03Well, I think all of you are
  • 09:05very familiar with diffuse three
  • 09:06and the spirit sites played an
  • 09:08important role with that trial.
  • 09:10It was stopped early.
  • 09:11It was a highly positive trial
  • 09:13published in New England Journal
  • 09:15Medicine and along with the dawn
  • 09:17trial which is going on at the same
  • 09:19time it led to immediate change
  • 09:21in clinical practice and stroke
  • 09:23guidelines with lives changed worldwide
  • 09:25throughout the world and in 2018 I
  • 09:29received the distinguished clinical.
  • 09:30Research Achievement Award and I
  • 09:32know the P eyes of the of the diffuse
  • 09:35three were barely proud of it,
  • 09:36as as was our whole network,
  • 09:38but that's the top on the top three of
  • 09:40all clinical stroke trials and US in 2018.
  • 09:44Second completed trial was
  • 09:46the teller rehab trial,
  • 09:47which was the first randomized trial of
  • 09:50liability patient for stroke patients
  • 09:52was published in JAMA Neurology.
  • 09:54The trial demonstrated that Tiller
  • 09:56rehab is not inferior to in clinic
  • 09:59therapy for improving our motor status
  • 10:01in patients who've had a recent stroke.
  • 10:04And with our experience with COVID,
  • 10:06it shows the future importance of
  • 10:09this technique is particularly
  • 10:10with those in general,
  • 10:11have limited ability to travel,
  • 10:13and there is two comments by PM Duncan
  • 10:17and Julie Bernhardt and stroke of 2021,
  • 10:20which said with the widespread
  • 10:23adoption of telerehabilitation
  • 10:24catalyzed by the COVID-19 pandemic,
  • 10:27this approach provides great potential
  • 10:29for improved care equity by addressing
  • 10:32the geographic you live far away from the.
  • 10:35Comprehensive site,
  • 10:36demographic and social economic barriers.
  • 10:43So. We all know about COVID.
  • 10:46It's impacted every one of our lives in
  • 10:49the conference here packed it personally.
  • 10:52Professionally,
  • 10:52with the health of their patients,
  • 10:55but it's had a tremendous impact on
  • 10:58clinical research and to Orient you to
  • 11:01this slide are are cute trouser on the
  • 11:03top that's most are prevention trials
  • 11:05or in the middle and the bars and
  • 11:08each one of these bars represents the
  • 11:10number of recruitments per month and
  • 11:13our recovery trials around the bottom.
  • 11:16And based upon what happened with COVID,
  • 11:18we made the decision to shut
  • 11:21down the network for safety.
  • 11:23Of the patients that we're trying to enroll,
  • 11:25but also the safety of our research
  • 11:27staff and we would then just from
  • 11:30about six day weeks completely
  • 11:32reconfigured the protocols of the trials,
  • 11:35how we were going to access patients,
  • 11:37how we were going to liver drug.
  • 11:39And how even did consent virtually
  • 11:42by E consent.
  • 11:44And we did that within a couple
  • 11:46months time such within 55 days we
  • 11:49had restarted the trials of a few
  • 11:52days later for the therapy trials,
  • 11:54but I think it shows how quickly
  • 11:57we could respond as network to a
  • 11:59really a crisis and how we could
  • 12:01redesign what we were doing to come
  • 12:04up with a better approach,
  • 12:05not just maybe for in this time of COVID,
  • 12:08but also trials in the future.
  • 12:10And you can see that we got back
  • 12:12up to recruitment pretty well,
  • 12:13although I would say that we're still
  • 12:15not quite at the rate that we were for
  • 12:18some of the trials prior to kovit,
  • 12:20and we're still in the midst of the pandemic,
  • 12:22as we well know.
  • 12:24So here are the trials,
  • 12:27but the completed trials already
  • 12:29talked about Diffuse 3.
  • 12:30But the ongoing trials have just
  • 12:33just a broad range of clinical
  • 12:35questions we're trying to answer.
  • 12:37So Crest two in Crest age.
  • 12:40We're looking at gradually rasterization
  • 12:43for asymptomatic chronic stenosis,
  • 12:45either by stenting or by endarterectomy,
  • 12:48and comparing that to best medical therapy.
  • 12:51Arcadia we're looking at cryptogenic
  • 12:53strokes and we're looking at patients
  • 12:56who have one of three cardiac
  • 12:58markers and then seeing whether
  • 13:00apixaban or aspirin is a better way
  • 13:02to prevent strokes and outcomes in
  • 13:05these patients are KSI is looking
  • 13:07at cognition in silent infarcts.
  • 13:10In their KD patients.
  • 13:11Save Smart is looking at a broad
  • 13:13range of the scheming stroke patients
  • 13:16and saying if we can identify
  • 13:18sleep apnea in the hospital,
  • 13:20does treatment using CPAP equivalent
  • 13:23improve outcome and also prevent
  • 13:26strokes better than just standard care?
  • 13:29Most is a trial that's trying to see
  • 13:32whether we can add something to TPA
  • 13:34given within three hours of onset and
  • 13:37improve re perfusion and outcomes.
  • 13:39The two agents are eptifibatide
  • 13:41which is affect platelet function in
  • 13:44Argatroban which is an anti thrombin
  • 13:46molecule and patience in this truck
  • 13:48can also can endovascular therapy.
  • 13:50In fact 40% of patients have transport
  • 13:53two and I acquire our two covered trials.
  • 13:57Transport.
  • 13:58Two is looking at.
  • 14:00Upper extremity motor recovery
  • 14:01in patients who've had a stroke
  • 14:04and we are comparing transcranial
  • 14:07direct stimulation plus modified
  • 14:09constraint to sham transcranial direct
  • 14:12stimulation plus modified constraint.
  • 14:15I acquire is a very exciting
  • 14:17trial for little babies.
  • 14:18You know, infants 818 months to
  • 14:21three years who had a stroke due
  • 14:23to an arterial blockage at some
  • 14:25point prior to that and then using
  • 14:28a very intensive rehabilitation of
  • 14:30six hours a day or different time.
  • 14:33Actually different amounts of rehabilitation,
  • 14:36and it's very specifically designed for kids.
  • 14:39It's like playing with them very
  • 14:41intensely or going through their
  • 14:42activities of daily living,
  • 14:43but doing it for six hours.
  • 14:45In a very concentrated way for four weeks,
  • 14:47and that's compared against standard therapy.
  • 14:50And then we follow up patients out
  • 14:52to six months and the control group
  • 14:54can actually then elect to go and get
  • 14:57the intensive therapy after that.
  • 14:58So it's a very satisfying trial for
  • 15:01parents with kids with young kids
  • 15:03with stroke about having something
  • 15:05that can maybe help their their young
  • 15:08young children aspire and Saturn aura
  • 15:11two prevention trials for ICH and.
  • 15:15Kevin Shaft here at at at Yale,
  • 15:17is the contact P for Aspire and here
  • 15:20we're looking at patients who've
  • 15:22had predominantly deep hemorrhage is
  • 15:25also have atrial fibrillation and
  • 15:27the decision is should we be using
  • 15:30at a pixel BAM or aspirin to prevent
  • 15:33bad vascular outcomes in the balance
  • 15:36between hemorrhage and also the
  • 15:39ischemic events.
  • 15:40Saturn led by Maggie Celine,
  • 15:43is looking at patients who have
  • 15:46global RICH S.
  • 15:47And then also have been on a statin
  • 15:49agent in time with their hemorrhage.
  • 15:51And here we are deciding whether
  • 15:53to keep him on or take them off.
  • 15:55Which is better? It's a very pragmatic trial.
  • 15:59Activating Achensee or two COVID
  • 16:01platform trials that involves
  • 16:03stroke net include stroke patients
  • 16:05but also include a number of other
  • 16:08networks across the country.
  • 16:10Fastest is the newest acute stroke
  • 16:11treatment and this is a trial focused
  • 16:14on patients with intra cerebral
  • 16:16hemorrhage and the treatment.
  • 16:17Here's we commented factor 7A
  • 16:20versus pussybow,
  • 16:21but it has to be given within
  • 16:22two hours of onset,
  • 16:23so one of the ways that we're doing that
  • 16:26is focusing on exception from informed
  • 16:28consent and also mobile stroke units.
  • 16:30And this is one of our global trials.
  • 16:32It's it's also taking place in Japan,
  • 16:35Canada and Europe.
  • 16:37And we're going to talk in more
  • 16:39detail about Captiva verifying
  • 16:41rapsodie to in just a moment.
  • 16:46So what is in the future?
  • 16:48What is in potentially in your
  • 16:50future if you're going to be at
  • 16:52one of the sites for these trials?
  • 16:53So let's talk first about Captiva.
  • 16:56Certainly they have the best
  • 16:59looking location for a trial.
  • 17:00If we could all do it there
  • 17:02and do it all year round,
  • 17:04but the piece for the trial,
  • 17:06Brian, who is is the first
  • 17:09nurse surgical P as a primary P
  • 17:12contact P for the trial Mark Cho.
  • 17:14It's also act as a P at the
  • 17:17medical versus South Carolina.
  • 17:18Sherry Yates is the statistical P
  • 17:21Renee is also another statistical
  • 17:24investigator and then Tonya
  • 17:26Larissa play important roles.
  • 17:27The study as well and again this is a
  • 17:31trial that has funding from the NIS,
  • 17:34but also has participation from
  • 17:36the industry and that Jackson
  • 17:38provides river rocks.
  • 17:40Abandoned funding for Pussybow and Astra
  • 17:42Zeneca is providing Thai capital or.
  • 17:47So this is a three arm trial.
  • 17:49Were trying to answer what's the best
  • 17:51way to prevent an ischemic stroke,
  • 17:54at least medical prevention with somebody
  • 17:56who has a high Gray into the cranial artery.
  • 18:00Stenosis associated with an ischemic stroke,
  • 18:02so we're gonna need a lot of
  • 18:05patients to address that.
  • 18:0616183 subjects with a symptomatic
  • 18:08infarct due to 70 to 99% of the
  • 18:12symptomatic inner cranial stenosis.
  • 18:14They have to have a non disabling
  • 18:16symptomatic infarct within.
  • 18:1730 days and it has to be one of these
  • 18:20arteries defined by these imaging techniques.
  • 18:23It's randomized in a one to one
  • 18:25to one and it's double blind.
  • 18:27And the three arms are tight.
  • 18:29Aguilar plus aspirin versus rivaroxaban
  • 18:32at a low dose versus aspirin
  • 18:35and clopidogrel versus aspirin,
  • 18:37which is really kind of considered the
  • 18:39standard of care right now for three months.
  • 18:41Although in this trial it goes out
  • 18:43all the arms go out to 12 months.
  • 18:45We also sampled for genotype,
  • 18:47which has to do with how literal
  • 18:50is metabolised and becomes active,
  • 18:52and this can vary with patients.
  • 18:55And then we do intensive risk
  • 18:57factor management.
  • 18:58For all of that,
  • 18:59all the arms just like insane person.
  • 19:01Press two and then the follow
  • 19:02up goes out to 12 months.
  • 19:06So why do a three arm study?
  • 19:08Well, it's timely and we have some
  • 19:10new information that's exciting
  • 19:12about ways that maybe we can improve
  • 19:14upon what we're already doing.
  • 19:16So, for example, we have great
  • 19:18data for capital and aspirin,
  • 19:20at least for the first several months.
  • 19:22For point enchants,
  • 19:23we have data for Chi, Cago,
  • 19:26and aspirin from the sales
  • 19:27and the print studies,
  • 19:29and we have data from about low dose
  • 19:31river rocks abandoned aspirin for
  • 19:33the compass and Commander HF trials,
  • 19:36and it's efficient 'cause
  • 19:37we have one control arm.
  • 19:39And the comparison is to the
  • 19:41completed role plus aspirin arm,
  • 19:43which is the control arm not
  • 19:45against the respective arms.
  • 19:46So we could come up with two
  • 19:48effective treatments and that
  • 19:49would be nice to have and we
  • 19:50have to decide which one to use,
  • 19:52but that would be a good problem to have.
  • 19:56Let's talk about Ty Cobb Award for those
  • 19:58who might not be as familiar with it.
  • 20:00It's a direct P2Y12 receptor antagonist.
  • 20:03It has maximal platelet reactivity
  • 20:06inhibition at one hour versus critical,
  • 20:09which is much longer.
  • 20:11It does not require the activation or the
  • 20:15metabolism of the critical like it does,
  • 20:18like it is for compatible.
  • 20:20And tackle is actually more
  • 20:22effective than compatible,
  • 20:23irrespective of the of the
  • 20:25carrier status or the genetics.
  • 20:27And that's true with a number of
  • 20:28different trials in cardiac trials.
  • 20:32Just want to point out the
  • 20:34the the area of interest.
  • 20:36The population interest for us is
  • 20:39this inter cranial artery disease
  • 20:41and this is from fails and if we
  • 20:43look at patients treated with Taika
  • 20:45galore versus placebo we see that
  • 20:48there is a strong protection of
  • 20:51prevention of stroke and the trike
  • 20:53Agler group in this particularly in
  • 20:56this group and also the event rate
  • 20:58is higher in this group than it is.
  • 21:00Overall, we know that this group is.
  • 21:03Particularly high risk group,
  • 21:04as we found in samples.
  • 21:10This is data from the compass trial,
  • 21:12which was more of a generalized trial.
  • 21:13How we take care of patients
  • 21:15with atherosclerotic disease
  • 21:17and preventing ischemic events,
  • 21:19and you see that for stroke,
  • 21:21it actually was effective.
  • 21:23Highly significant difference.
  • 21:24The reason why this is such a low rate
  • 21:26is because a lot of these patients
  • 21:28didn't have a stroke to start with,
  • 21:30but the Nice comforting thing is that
  • 21:32the hemorrhage intercell heavy drag
  • 21:34was similar between the two groups,
  • 21:36although there was more bleeding
  • 21:38in other places.
  • 21:42So what, uh? Why are we doing your 12 month?
  • 21:46Treatment rather than three months.
  • 21:48Well, the rates of recurrent
  • 21:50stroke in the territory.
  • 21:51That's not a garden where the
  • 21:53double from 3 to 12 months in
  • 21:55samples and half of US stroke.
  • 21:56Neurologists surveyed always use capital
  • 21:59in asper for longer than three months.
  • 22:02But this is even I think,
  • 22:03more interesting.
  • 22:04You may not know that in Sampras
  • 22:06there were fifty medical armed
  • 22:08subjects who took Lipidic own
  • 22:09aspirin longer than three months
  • 22:11because of cardiac clearance.
  • 22:13Maybe they had a recent standards
  • 22:14that with the last couple of years,
  • 22:16but you see that those people that
  • 22:18had the treatment for more than
  • 22:20three months had A at a decreased
  • 22:23primary endpoint compared to
  • 22:24the ones who got the traditional
  • 22:27treatment within three months.
  • 22:29And there was a little bit increase,
  • 22:31but not significant difference
  • 22:32in major hemorrhage.
  • 22:36So what's captivus timeline?
  • 22:37It's planned for five years.
  • 22:39We're going to six months startup,
  • 22:4138 months of woman,
  • 22:4212 months to follow last,
  • 22:44patient out, and then data analysis.
  • 22:46We hope to get 4.6 subjects
  • 22:49per site per year.
  • 22:51We're going to need 115 sites.
  • 22:53Site selections essentially done,
  • 22:54and we hope to be starting here in 2022.
  • 22:58Investigating will probably be
  • 23:00in the first several months,
  • 23:022020 for sure.
  • 23:06So let's talk about the other next new study,
  • 23:09which is verify I happen to
  • 23:12really also like there there.
  • 23:15Dear Monica, for the study and it's
  • 23:17a validation of early prognostic
  • 23:20data for recovery outcomes after
  • 23:22stroke for our future higher yield
  • 23:25trials and the title does say at
  • 23:27all in terms of what they're trying
  • 23:29to come here trying to accomplish.
  • 23:31So you can see here the pies on the left,
  • 23:33pushing country as a contact P.
  • 23:35Steve Cramer, Cathy Stanier,
  • 23:37Telegol and then key other people on the
  • 23:40other side in terms of project managers
  • 23:42and statistics and data management.
  • 23:47So what are the deliverables I'm
  • 23:49going to start with the deliverables
  • 23:51and will go into the details.
  • 23:52What they want to do is to have a
  • 23:55reliable way to predict patient
  • 23:57outcomes soon after ischemic stroke,
  • 23:59such that we could stratify patients
  • 24:02into the right type of therapy approach
  • 24:05and also design trials much better,
  • 24:08because if you're going to take a
  • 24:10person who's not going to respond
  • 24:11with physical therapy or whatever,
  • 24:13why would you want to put them
  • 24:15in trial testing that?
  • 24:16But if you have somebody who know,
  • 24:18tends to get better,
  • 24:20then can we improve upon that, can we?
  • 24:22And when should we intervene?
  • 24:24But stratification will be helpful.
  • 24:26It's sort of like the difference
  • 24:28when the acute stroke trials where
  • 24:29we know that when you have a clot
  • 24:31there and we're testing things
  • 24:33that remove clots will likely
  • 24:34going to have a positive outcome.
  • 24:37Whereas we include patients
  • 24:38that don't have a clot there.
  • 24:40And we're testing the clock removal device,
  • 24:42it's going to be harder to find a benefit.
  • 24:45And then eventually,
  • 24:47we'd like to enable personalized
  • 24:49rehabilitation therapy for the long term.
  • 24:52So the primary objective is to validate
  • 24:54the most promising biomarkers and
  • 24:56motor recovery after ischemic stroke.
  • 24:58In this first large scale perspective,
  • 25:00generalized data set.
  • 25:01So the idea is 557 ischemic stroke patients,
  • 25:05but they also want to collect and we
  • 25:08want to collect data on hemorrhage
  • 25:09patients and exploratory factions,
  • 25:11so they'll be 100 intracellular
  • 25:13hemorrhage patients as well.
  • 25:17So what is the first biomarker?
  • 25:19Well, the first fire marker is trans
  • 25:22magnetic stimulation of the escalation,
  • 25:24absolution or motor cortex.
  • 25:26So you stimulate it and then you see
  • 25:29if you get a motor evoked response
  • 25:31in the extent to carpi radialis
  • 25:34and the first dorsal interosseous,
  • 25:36and that MVP plus means yes,
  • 25:39some of those pathways are
  • 25:40intact if you stimulate it,
  • 25:42you get a response and it means you
  • 25:45have a functionally intact system.
  • 25:48The second biomarker is looking at the
  • 25:51cortical spinal pathways themselves,
  • 25:53and looking at the DWI lesion
  • 25:56load along that pathway,
  • 25:58and basically the more lesion you have,
  • 26:01the more structural damage and Jelly
  • 26:03the poor you're probably going to do.
  • 26:07So here's hypothesis,
  • 26:09aimed 118 is to look at the
  • 26:12relationship between the upper motor,
  • 26:15upper extremity motor impairments were
  • 26:17baseline in 9090, days after stroke.
  • 26:20The upper extremity was called
  • 26:22defense score and and it's going
  • 26:24to depend upon whether it's
  • 26:26your MVP plus or any P negative.
  • 26:28Whether you have a motor
  • 26:30response but transmitting exam,
  • 26:32and here are some actual data
  • 26:34where you can see here that those
  • 26:36that have a positive response.
  • 26:38Are much likely to have a good 90
  • 26:40day upper extremity film score,
  • 26:43and those that don't have a positive are
  • 26:46much less likely to have a good score.
  • 26:52Also, we're going to look at the
  • 26:54relationship between MRI measured
  • 26:56the lesion volume and the 90 day
  • 26:59opportunity motor impairment,
  • 27:01but how it reflects and depends
  • 27:03upon the MVP, the stimulation.
  • 27:05So here's some more data
  • 27:07where you can see that yes,
  • 27:09the more you lesion load you have
  • 27:11the jungle worse you do at 90 days,
  • 27:14but if you got an intact
  • 27:16stimulation response while there's
  • 27:17still a little bit of a decline,
  • 27:20it's a much better response.
  • 27:22Then it is when you don't have a response.
  • 27:28Hypothesis 2 is they're going to use a
  • 27:30Prep 2 prediction tool which will try to
  • 27:34accurately predict the likelihood of a
  • 27:36good upper extremity functional outcome.
  • 27:38That's decide defined by the
  • 27:41active research ARM score,
  • 27:43and they're going to be able to do that,
  • 27:45hopefully for more than 70% of patients.
  • 27:47And so here you see that they use
  • 27:49something called the safe score.
  • 27:51Safe Score is a shoulder abduction
  • 27:54finger extension extension score,
  • 27:56and the higher the score, the better.
  • 27:58More likely to have a good outcome.
  • 28:00So if you're more than equal
  • 28:01to five and you're young,
  • 28:03it's really going to be doing pretty
  • 28:05well predicted by this score.
  • 28:06If you're not as young,
  • 28:08well then and you have to divide
  • 28:10up a little bit differently.
  • 28:12You may tend to fall a little bit.
  • 28:14Not quite as good, but still pretty good.
  • 28:16If you don't have a good baseline score,
  • 28:20but you got intact magnetic
  • 28:23stimulation response,
  • 28:25generally you still may fit up in
  • 28:27a good response, but if you don't,
  • 28:30and depending upon how severe
  • 28:32stroke scale score is,
  • 28:33you also fit into these categories,
  • 28:35so it's idea is trying to put people
  • 28:38in categories within a couple days
  • 28:41of admission to the hospital.
  • 28:46Here are the key eligibility criteria.
  • 28:48So age 18 years older unilateral stroke
  • 28:51due to ischemic or hemorrhage and the safe
  • 28:54scores gotta be lasted an equal to 8,
  • 28:56because if it's more than eight,
  • 28:58you're generally gonna have
  • 28:59a pretty good outcome.
  • 29:00And this also excludes full or nearly
  • 29:03full motor strength in both the shoulder
  • 29:06abduction and finger extension.
  • 29:08Key thing is you gotta get them
  • 29:11consented within 48 hours to 96 hours,
  • 29:13so here's a biomarker study or
  • 29:15recovery biomarker study that's really
  • 29:17a lot like an acute stroke study
  • 29:19and that we're trying to get people
  • 29:21involved within the first few days.
  • 29:26Here are the different aims and I'm
  • 29:27not going to go through this in detail,
  • 29:29but just to point out the different.
  • 29:32Measurement outcomes to address each
  • 29:34aim so the upper extremity of people
  • 29:38Myers scale the upper motor action
  • 29:41research arm test the motor activity
  • 29:43log score and then looking at all of
  • 29:46these aims and these outcome measures
  • 29:49with intercell hemorrhage as well.
  • 29:54Again, that first day visit getting
  • 29:57consent within 96 hours and then
  • 29:59some also visits that occur very
  • 30:01quickly with a lot of assessment,
  • 30:04which means you got to get an MRI of the
  • 30:06brain and the transmitting stimulation
  • 30:08and the participants only enrolled if
  • 30:11they've gotten the TMS stimulation
  • 30:14or they've had the MRI sequence.
  • 30:17And then we look at any adverse
  • 30:20events following that stimulation,
  • 30:23and then we do a day 30 visit
  • 30:26and a day 90 visit and the study
  • 30:28essentially is over a day 90.
  • 30:32So. It's moved very quickly.
  • 30:34We just got the award in September.
  • 30:37We're making a lot of progress.
  • 30:39We've also just put in the request
  • 30:41of the purchased as the medic
  • 30:43Magnetic Stim devices for the sites,
  • 30:45and the idea is we would hopefully
  • 30:48be having sites ready to be trained
  • 30:51in spring and maybe enrolling
  • 30:53the first patient by summer.
  • 30:56And just a few comments about this trial.
  • 30:59It's a really A to biomarker study.
  • 31:02It's not a trial where we're
  • 31:03doing intervention,
  • 31:04so it actually you can enroll
  • 31:06people in this trial while also
  • 31:09being in other trials because it's
  • 31:11not affecting the outcome per say.
  • 31:13And this will be a decision
  • 31:15by other Pis of other trials.
  • 31:17How much overlap?
  • 31:19But there's no,
  • 31:20there's no ethical reason or
  • 31:22statistical reason why people
  • 31:24couldn't be in both trials,
  • 31:26so again,
  • 31:26this will be hopefully happening very soon.
  • 31:32The last time we talked about is Rhapsody 2,
  • 31:35which again should be coming
  • 31:37in 2022, probably later.
  • 31:39It's a neuroprotective trial in setting
  • 31:41of patients undergoing re profusion
  • 31:43therapy within 24 hours of onset,
  • 31:46whether by a lytic drug or
  • 31:48by end of vascular therapy.
  • 31:51It was approved by council in 2021.
  • 31:54It also has gotten approval the
  • 31:57CRB and FDA is also approved the
  • 32:00protocol pending a few outstanding
  • 32:02items and the company is gearing
  • 32:04up to manufacture the drug at the
  • 32:07SIBO and it is a global trial
  • 32:09and the outside of U S sites.
  • 32:11They're also submitting their regulatory
  • 32:12documents and grant applications,
  • 32:14so big trial in a lot of places.
  • 32:19So what is the neuroprotective agent? Well,
  • 32:22it's a mutated form of activated protein C,
  • 32:26and those who remember clotting cascade
  • 32:28activated protein C is important part
  • 32:31of anticoagulation within the blood.
  • 32:33But if you replace 3 lysine residues
  • 32:38here with three alanine residues,
  • 32:41it basically eliminates almost
  • 32:43all of the anticoagulant activity,
  • 32:46but preserves cell signaling activities.
  • 32:49So what are those?
  • 32:51Well, there's several.
  • 32:52It can be vascular protective
  • 32:54at the end of helium and helps
  • 32:57stabilizes the blood brain barrier.
  • 32:59It affects neurons and that could be
  • 33:02under protective effect with neuronal
  • 33:04function and promotes neurogenesis.
  • 33:06It's anti-inflammatory and again
  • 33:08the mutant form has very limited,
  • 33:11a much lower amount of any
  • 33:13coagulant activity.
  • 33:17There was a phase two trial of
  • 33:19this agent done as part of the
  • 33:21neuron next network and I just
  • 33:23showed you the bottom line here,
  • 33:25which showed that in patients
  • 33:27who got the active drug,
  • 33:30the mutant APC there were less
  • 33:32bleeding in the brain of an
  • 33:34ischemic stroke compared to
  • 33:36placebo as measured by MRI.
  • 33:41So the primary aim of this trials
  • 33:43to evaluate the safety and efficacy
  • 33:45of the mutant APC for acute ischemic
  • 33:48stroke looking at the orbital shift
  • 33:50analysis at the three month time
  • 33:53window and the key secondary outcome,
  • 33:54is the proportion of patients
  • 33:56alive and without interest.
  • 33:57Several hemorrhage at 30
  • 33:59days after ischemic stroke,
  • 34:00that incenses, our safety outcomes.
  • 34:04So those are three new trials,
  • 34:07but now I'm going to switch gears
  • 34:09and talk about platforms and I can
  • 34:11ask how many people have had dove
  • 34:14off a high board before and I have,
  • 34:17but I've never done it at those big
  • 34:20platforms that are 30 or 100 feet
  • 34:22high and and that seems pretty scary,
  • 34:24but the higher the platform,
  • 34:27the more you can do before you hit the water,
  • 34:29whether it's you know four twists
  • 34:31or four turns.
  • 34:32Whatever you watch the Olympics,
  • 34:33you see that.
  • 34:34So we're talking about platform trials.
  • 34:36It could be a little bit daunting,
  • 34:38a little bit scary,
  • 34:39but there's a whole lot of things
  • 34:42we could accomplish by the time
  • 34:44we finished the platform trial.
  • 34:47So let's talk about why this platform
  • 34:50trial is happening in stroke.
  • 34:52Let's go back in time to 2018,
  • 34:54where Diffuse Three was finishing up.
  • 34:58Don was finishing up,
  • 34:59and there was such excitement in the field.
  • 35:01It was only a couple of years before that,
  • 35:02and they've asked her trials were
  • 35:04positive was really geared up,
  • 35:05and lots of people had lots of ideas,
  • 35:08and so there was this plethora of trials
  • 35:11that are being proposed and sent to an INDS,
  • 35:14and you can see them here a lot.
  • 35:18And you can see the one by the domain of the.
  • 35:21Those that were kind of expanding.
  • 35:23The indication new things added and
  • 35:25then system kind of type type trials
  • 35:28like in the prehospital setting.
  • 35:30Well, and I and D as responsible
  • 35:33to fund a lot of things and a lot
  • 35:35of stroke thinks and they can't
  • 35:37just do endovascular trials.
  • 35:38They said, well, Gee,
  • 35:39we can't just do all these in the
  • 35:41back massacre trials proposed
  • 35:43would be doing nothing.
  • 35:44But is there a better way to answer
  • 35:48the questions that are being proposed?
  • 35:51So here is the current approach.
  • 35:52Back in back, several years ago, Mr.
  • 35:55Clean comes out and says hey,
  • 35:56we know endovascular works in alternately
  • 35:59population and we have done and diffuse.
  • 36:02Well,
  • 36:02that's still work.
  • 36:03We were treating a little later
  • 36:05if we can select out patients
  • 36:07by imaging and clinical exam.
  • 36:09And then you can do another
  • 36:10trial and another trial,
  • 36:11and it keeps extending the indication,
  • 36:13but it takes longer and longer
  • 36:15and longer to get it done.
  • 36:17So Janet Woodcock,
  • 36:19the FDA in 2017 said,
  • 36:21you know our clinical trial system
  • 36:24of kind of just doing one trial after
  • 36:27another is broken and we need a new ways.
  • 36:30And she noticed used to master
  • 36:31protocols or protocol for trials
  • 36:33where you look at multiple therapies
  • 36:35for single disease or single
  • 36:37treatment and multiple diseases and
  • 36:39new platform or neutral networks
  • 36:40really are the future of where we
  • 36:43need to go with clinical trials.
  • 36:46And there's several different
  • 36:48types of trout platforms,
  • 36:49so there's an umbrella trial.
  • 36:52I'm going to type platform when you have
  • 36:54multiple treatments for one disease,
  • 36:56and that's actually one of those
  • 36:58had been proposed earlier in stroke
  • 36:59net for very for neuroprotection,
  • 37:01there's basket trials where you have
  • 37:04multiple diseases of one treatment.
  • 37:06Let's say we're going to look at a
  • 37:08traumatic brain injury, intercell,
  • 37:10hemorrhaging, ischemic stroke,
  • 37:11and using our protective agents,
  • 37:13just for example.
  • 37:14Minesweeper treatment as you
  • 37:16got one treatment, one disease,
  • 37:18but you're trying to identify
  • 37:20multiple subgroups.
  • 37:21Big strokes, small strokes,
  • 37:23strokes of a certain nature,
  • 37:25certain certain type of population.
  • 37:28That's the minesweeper approach,
  • 37:29and that's kind of what we were
  • 37:31trying to get at with some of these
  • 37:33trial proposals back in 2018.
  • 37:38So here's our FDA guidelines.
  • 37:40Guidances that came out about how to do
  • 37:43these trials and and a lot of it started
  • 37:46out quite frankly in the cancer area.
  • 37:48In fact, you can see them then the platform
  • 37:52trials really started in the cancer
  • 37:54area back in 2005 with prostate cancer.
  • 37:57They've done a lot of
  • 37:59patients since that time.
  • 38:00The I spy, two with breast cancer 2010,
  • 38:04but then you can see it starts to
  • 38:07accelerate here in 2019 for glioblastoma.
  • 38:092020 for a less 2020 for pain and that.
  • 38:14Here, hopefully in 2022, four stroke.
  • 38:19So one of the advantages of master
  • 38:22trial protocols well eliminates the
  • 38:24cost and duplication of resources
  • 38:26with traditional freestanding
  • 38:27parallel group randomized trials.
  • 38:30It has some of the.
  • 38:32Advantages of the stroke net that
  • 38:33we talked about at the beginning.
  • 38:35You can have the infrastructure in
  • 38:36place and just keep adding things in.
  • 38:39You can also compare multiple invention
  • 38:41interventions crossarms you can
  • 38:43look at subgroups of patients with
  • 38:45distinct or related clinical features.
  • 38:47You can minimize downtime between
  • 38:50trials you share control groups,
  • 38:52you drop arms early when treatments fail
  • 38:54and you combine promising treatment arms.
  • 38:59So an idea said this is where we want to go,
  • 39:02so we're going to put out a special
  • 39:05notice of interest to do this for stroke,
  • 39:08and so a number of the investigators
  • 39:10in stroke net took this on and actually
  • 39:13recruited people from the field as well.
  • 39:16You know, from the end of Ascot community
  • 39:19in general to put a really terrific team
  • 39:21together and and put an idea of how
  • 39:23we want to do this that was submitted.
  • 39:25We've gotten some great feedback on that,
  • 39:28and I think the future looks bright.
  • 39:30For having this happening,
  • 39:31hopefully you know starting this
  • 39:33in some phase of things in 2022.
  • 39:36So here's the step platform.
  • 39:40So it's made up of three components,
  • 39:43so the stepstone or sort of like what
  • 39:46extension of endovascular therapy should we.
  • 39:49Looking at small stroke scale scores,
  • 39:51big chords, other potential options.
  • 39:55Step Smart is how can we add
  • 39:57something to this,
  • 39:58whether it's a new drug or protective drug,
  • 40:01a new device,
  • 40:02a new way of doing,
  • 40:03let's say anesthesia couple different
  • 40:06things are in this step smart
  • 40:08and the step lively is.
  • 40:10How can we do companion trials
  • 40:12that maybe look at systems of care
  • 40:15identifying these patients in the field?
  • 40:17Again, a range of opportunities,
  • 40:20but all trying to focus on patients who
  • 40:22have a clot in an artery that we can
  • 40:24see that we want to do something about.
  • 40:30The other idea about this,
  • 40:32we want to take the databases
  • 40:34that we're already collecting
  • 40:35and maybe build off of those,
  • 40:37rather than creating a whole new database.
  • 40:39So make it easier on sites to already
  • 40:41take the data they're collecting
  • 40:43and use it for these trials as well.
  • 40:48Here's a little bit of
  • 40:50these overall organization,
  • 40:51and you can say it's pretty extensive.
  • 40:54You have your executive committee
  • 40:55and operations group here,
  • 40:57but there's the group that
  • 40:59worked on the actual kind of
  • 41:01trial ideas and systems of care.
  • 41:03But then there's a whole bunch of
  • 41:06corps recruitment data imaging,
  • 41:08and the vascular quality statistical core.
  • 41:11And then it's all still connected
  • 41:14with the stroke net organization and
  • 41:16it's overseeing again by the DSMB.
  • 41:19And the central IRB. And again, it's a.
  • 41:23It's a great infrastructure and we
  • 41:26hope to get it started here soon.
  • 41:29So let's talk about what's the first step.
  • 41:31Well, the first step is to get the
  • 41:34database in place and the entry of
  • 41:37patients who have a visualized clot in
  • 41:40the artery with an ischemic stroke.
  • 41:42That's eligible for endovascular therapy.
  • 41:45That's kind of what we were
  • 41:47looking for to start with,
  • 41:48and then we start adding in their respective
  • 41:52trials into that baseline infrastructure.
  • 41:55So again,
  • 41:57expansion into different areas.
  • 42:00And then the rest is really work
  • 42:02in progress and and people are
  • 42:04working very hard and let some great
  • 42:06ideas already out there with the
  • 42:08posed with from our stroke net.
  • 42:10Colleagues throughout throughout EU.
  • 42:12S.
  • 42:14So that's what's coming to us,
  • 42:16but I I wanted to just talk about
  • 42:18some of the challenges again
  • 42:19that we've faced as a network.
  • 42:21All of you have been through this,
  • 42:22so first one is COVID and
  • 42:24it's still a challenge.
  • 42:26It's still affecting us in multiple ways
  • 42:28in getting patients enrolled in trials,
  • 42:31and I think it's going to still be
  • 42:33like that for at least this next year,
  • 42:35but hopefully it will subside and
  • 42:37the stress of COVID will have made
  • 42:39us a stronger and better network.
  • 42:42There's other,
  • 42:42though challenges about how we interface
  • 42:45with our colleagues in other specialties,
  • 42:47particularly cardiology
  • 42:48and Kevin and colleagues.
  • 42:51With this fire and Maggie
  • 42:53and colleagues would Saturn.
  • 42:54I really struggled with the fact
  • 42:56that cardiologist had some very
  • 42:58definite ideas about how their
  • 43:00patients should be managed.
  • 43:01For example,
  • 43:02you know everybody should be on
  • 43:04a statin if they've had a cardio
  • 43:06cardiovascular problem and what
  • 43:08they don't understand is that
  • 43:09it may not be the same formula.
  • 43:11For patients who have very
  • 43:13specific issues such as low bar,
  • 43:15icah and so we need to educate them,
  • 43:19we need to have conversations with
  • 43:21them and we need to publish in order
  • 43:24to get that equipoised among our
  • 43:26cardiology colleagues and not just ourselves.
  • 43:29The other thing is that I see patients
  • 43:31who are very severely affected
  • 43:33and so enrolling these patients
  • 43:35adventure trials is harder than it
  • 43:37is for most of these key mix trucks,
  • 43:39and we're looking at many
  • 43:40different ways to approach this.
  • 43:42Spanning are expanding
  • 43:43our inclusion criteria,
  • 43:45but also how we go about
  • 43:47enrolling these patients.
  • 43:49Another big issue with acute
  • 43:51trials is recruitment of patients
  • 43:54outside of business hours.
  • 43:56So in the most trial,
  • 43:57recently took a survey and found that
  • 44:00just about a little bit more than
  • 44:02half of sites were only recruiting
  • 44:04subjects during Monday through Friday,
  • 44:06Monday and business hours and their
  • 44:09enrollment rate in the trial was
  • 44:12about half that of those sites that
  • 44:15recruit outside of those those days and 24/7.
  • 44:18So we need to find ways to address this.
  • 44:22How to address this call?
  • 44:23It's an expensive to Burditt,
  • 44:25but if we're going to be successful
  • 44:27acute stroke trials and recruitment,
  • 44:28we didn't need a whole bunch
  • 44:30more sites or we need the sites
  • 44:32that are up most of the time.
  • 44:35I think though the biggest
  • 44:38challenge I think with COVID.
  • 44:40Relates to the overload burning loss of
  • 44:42study coordinators across clinical research.
  • 44:45In general. It's not just for stroke,
  • 44:47but for all of us.
  • 44:50What's happened here is though,
  • 44:51people get burned out and then you
  • 44:54have to recruit a new coordinator,
  • 44:56and that person is less experienced
  • 44:59or you can't find a new coordinator,
  • 45:02so they'll coordinator that was doing
  • 45:04three trials is now doing 5 trials,
  • 45:06which then leads to them getting burned out.
  • 45:08And also maybe not as good a follow
  • 45:10ups and doing the follow ups at
  • 45:12three months and six months because
  • 45:14they're trying to do 5 trials,
  • 45:16or the three.
  • 45:17And so this is a really big issue.
  • 45:20Is not anyone great solution to it?
  • 45:22We've actually surveyed the
  • 45:24coordinators and most of you have
  • 45:26probably filled something like this
  • 45:27out over the last week and we're
  • 45:29going to be talking about a webinar
  • 45:31next week for stroke that about what
  • 45:33the data shows and talking about.
  • 45:35Maybe some also potential solutions.
  • 45:40For those of you who maybe
  • 45:42who like movies and when.
  • 45:43I look at some cool videos,
  • 45:45either the trials,
  • 45:46the trial leaderships have come up
  • 45:49with some really cool innovative
  • 45:51videos of how to recruit patients,
  • 45:53explain trials,
  • 45:54explain exception from informed consent,
  • 45:57how to train people and to
  • 45:59enroll people in trials,
  • 46:01and so if you've got a chance,
  • 46:02go on our website,
  • 46:04you will see the the respective
  • 46:06videos on their respective trials,
  • 46:08and there's some really good I think.
  • 46:10Ideas there,
  • 46:11and if you're planning a trial,
  • 46:12this is a great place to start
  • 46:14to see how you can do this well.
  • 46:19The last thing I'm going to bring up
  • 46:22is that it's not just about stroke net.
  • 46:26We are we have a global problem stroke
  • 46:28and we need all of our colleagues from
  • 46:31around the world pulling together
  • 46:33to solve these questions and one
  • 46:35of our goals at the beginning and
  • 46:37I stroke networks establishment.
  • 46:38The global network of national
  • 46:40stroke networks and working with our
  • 46:43colleagues in Canada and UK and Europe.
  • 46:45Initially we begin the gains network and
  • 46:48we have a website which link is there.
  • 46:51It's been a terrific forum for
  • 46:53discussion of potential trial proposals,
  • 46:55educational efforts for development,
  • 46:57young investigators,
  • 46:58and planning for the future of
  • 47:01collaborative stroke research.
  • 47:02There's actually 23 national
  • 47:04global networks that participate.
  • 47:06Currently,
  • 47:07we have regular recording meetings
  • 47:09of the Executive Committee,
  • 47:10as well as in person,
  • 47:11which was prior to COVID and
  • 47:14virtual meetings for Members,
  • 47:15and we actually have a forum where we
  • 47:17talk about new trial ideas globally,
  • 47:20or when people are looking for
  • 47:21other countries that may want
  • 47:22to participate in there.
  • 47:23File,
  • 47:24and that's really been been
  • 47:26actually great sessions who all
  • 47:28welcome to that that's published
  • 47:31and publicized through stroke net.
  • 47:32So if you want to listen to that,
  • 47:34you have here some really good
  • 47:36interesting ideas for the future,
  • 47:37and we've already moved to several
  • 47:40global trials within stroke debt.
  • 47:41Arcadian, Saturn.
  • 47:42Both had Canadian sites and
  • 47:45the improved Rhapsody too,
  • 47:46as well as the ongoing fastest
  • 47:49trial or global trials.
  • 47:51So, just to summarize,
  • 47:53political stroke networks are the present
  • 47:55future of clinical stroke trials.
  • 47:58You don't have to restart a network
  • 47:59every time a new trial is proposed.
  • 48:02But there's always things that happen.
  • 48:04We need to be flexible and nimble.
  • 48:05Response to events like COVID.
  • 48:08There'll be other things in the future,
  • 48:09hopefully like COVID,
  • 48:11but you always know there's
  • 48:13something that will happen.
  • 48:15We can answer clinical stroke
  • 48:17questions better and more quickly
  • 48:18with global cooperation in isolation,
  • 48:21so that's one of our future goals
  • 48:23as a network and as our global
  • 48:25connection of networks.
  • 48:27But exciting new trials are
  • 48:28coming to a site near you,
  • 48:30and we also look forward to exciting
  • 48:33new ideas for trials from our RCC
  • 48:36sites throughout the country.
  • 48:37I think we've got a great pipeline.
  • 48:39We've got great people and just just so
  • 48:41proud to be part of this wonderful network.
  • 48:43Thank you so much.
  • 48:45Joe, thank you so much for that.
  • 48:47It was an amazing overview of
  • 48:49what's coming up through stroke net.
  • 48:51I don't see any questions in the chat yet,
  • 48:53but I encourage people to put
  • 48:55them in if they have them.
  • 48:57Joe, do you see the network expanding
  • 48:59as all of these new trials come online?
  • 49:03I well you you have to ask me and I
  • 49:05and DS but just to give you an idea,
  • 49:08what's happening is NINDS is
  • 49:10doing an external review of all
  • 49:13of their different networks,
  • 49:15so next which many of you also apply
  • 49:18part out and and I stroke net are the
  • 49:20two that are being looked at right now.
  • 49:22And believe me we give them more
  • 49:24data than they probably have been
  • 49:25like drinking from a fire hose and
  • 49:27what they're going to try to do
  • 49:28in this committee is saying paper
  • 49:30what's working well and what and
  • 49:31what do we is a network feel like it?
  • 49:33Working well and what would we like to
  • 49:36do better and and how do we solve some
  • 49:39of the issues like the coordinated burden?
  • 49:41You know?
  • 49:42How do we support people to get
  • 49:44recruitment more effective?
  • 49:45So I I don't think will probably
  • 49:48change the number of Arc they could.
  • 49:50Maybe add one or so besides 24,
  • 49:53maybe get back to 25,
  • 49:55but I don't see that changing.
  • 49:57I think the number of sites we
  • 49:59already had 280 and we don't really
  • 50:02utilize all those 280 as well.
  • 50:04As we could,
  • 50:05but I think the expansion will be if
  • 50:08we do something is how we coordinate
  • 50:10with other networks and that is.
  • 50:13That's a challenge because you
  • 50:14have to figure out how you get
  • 50:16money from different sources in
  • 50:18different countries that can be
  • 50:20approved to do the same project,
  • 50:21and so that's something
  • 50:22we've been struggling with.
  • 50:23As in the game's leadership group,
  • 50:25but I think that would probably be the
  • 50:28biggest potential for maybe expansion.
  • 50:32And I have a.
  • 50:34It's a rather provocative question,
  • 50:35but when you showed that slide
  • 50:38of other platform clinical trials
  • 50:41in a myriad of other diseases.
  • 50:44You know, it just seemed to me
  • 50:46that those are still diseases
  • 50:48that we don't have effective
  • 50:50treatments for in many cases.
  • 50:52Can you or are there any success stories
  • 50:56from from that platform approach?
  • 51:00I think that the adaptive adaptive trials,
  • 51:03which is kind of a little bit of a platform
  • 51:06had been very successful in cancer.
  • 51:08I think they that's where that's been.
  • 51:11Some of the newer ones are.
  • 51:12They're only you know, a year or so old,
  • 51:14so we don't know how they're going to
  • 51:16pan out like prickly blastoma or pain.
  • 51:19But I I think the future is bright,
  • 51:22but we won't know.
  • 51:23I think for another ten years,
  • 51:25how some of those other
  • 51:26things are going to workout.
  • 51:28You really need a.
  • 51:29You need a 10 year time.
  • 51:30Window to see how I platform is.
  • 51:32Actually I think you know doing.
  • 51:35I I will anticipate the one of the things
  • 51:38you were talking about is that with
  • 51:40stroke we've gone from an untreatable
  • 51:42disease 12 highly treatable disease,
  • 51:45both acute and prevention,
  • 51:48and now even recovery.
  • 51:50We got a really exciting to do paper
  • 51:52that just came out from one of our
  • 51:55members who out stronger Coop past.
  • 51:57But I mean what?
  • 51:58What a legacy to have such a paper
  • 52:00that came out within just a few weeks
  • 52:02of you know him passing but there's
  • 52:04a lot of excitement in recovery.
  • 52:07We and this is my opinion.
  • 52:09This is not anybody else's opinion,
  • 52:11but.
  • 52:12I think we're going to come up,
  • 52:13get up against biological limits
  • 52:16for acute just like in cardiology.
  • 52:18If you look at cardiology,
  • 52:19there hasn't been a major acute advance
  • 52:23beyond the RE perfusion that we
  • 52:25talked about for probably 10-15 years
  • 52:28and we're still in the Golden Age,
  • 52:31so we're going to get better and we get
  • 52:33more extension and identify groups and
  • 52:35maybe add things that can improve things.
  • 52:37But you know,
  • 52:38I do think there's a timeline on that,
  • 52:40and maybe you know 1015 years.
  • 52:43So which at point at which point
  • 52:46defined the small tiny benefit?
  • 52:48She would need tens of thousands
  • 52:50of patients which we need to have
  • 52:52to have huge big global trials.
  • 52:54I think prevention, we still are.
  • 52:57We still learning.
  • 52:58We probably a little bit more opportunities,
  • 53:00but we're still.
  • 53:01We've made a lot of progress
  • 53:03there and and a lot of it is
  • 53:05changing our lifestyles as much as
  • 53:07adding another another drug and.
  • 53:08And that's a hard thing to do.
  • 53:11I think the biggest timeline is recovery.
  • 53:13I mean,
  • 53:14we there's so much we're learning
  • 53:15about how the brain recovers,
  • 53:17and I think that has a much larger timeline,
  • 53:20quite frankly, but that's just my opinion.
  • 53:27A question from Shadi.
  • 53:31Do you anticipate that the platform
  • 53:33trial design will be used for
  • 53:35prevention and recovery trials as well?
  • 53:37Hi hi uhm. And probably probably not I,
  • 53:44I think with anything you want to
  • 53:46first Test something out and in.
  • 53:48In some respects the platform was
  • 53:51in response to this overwhelming
  • 53:53excitement and number of proposed ideas.
  • 53:56In the end of Vascular area,
  • 53:58which they and some of those trials are going
  • 54:00on independent actually funded by industry.
  • 54:03I don't think that, but if it turns out
  • 54:06to be a really good successful situation,
  • 54:09then you know, but it's.
  • 54:10The fundamental thing is
  • 54:12endovascular treatment.
  • 54:13Things added with preventions,
  • 54:15you're often talking about
  • 54:17different population of patient,
  • 54:18different subgroups.
  • 54:19That makes it harder, and so I think it
  • 54:23would be more of a challenge I recovery.
  • 54:27That may be placed in the future.
  • 54:30We could go to.
  • 54:31I think I would say more recovery than
  • 54:34prevention just at first question.
  • 54:36It's really good question,
  • 54:37shoddy,
  • 54:37but that's just kind of my
  • 54:39gut reaction to that great.
  • 54:42Alright, I'll hand things back over to Shadi.
  • 54:48Hey, thank you so much Doctor
  • 54:50Broderick and Doctor Furey.
  • 54:52We've had very informative presentations
  • 54:54and excellent discussions so far.
  • 54:57This now brings us.