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

Transcript

• 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.