2025
719-P: Oral Disposition Index (oDI) as an Outcome Measure in Type 1 Diabetes (T1D) Clinical Trials—Evidence from Stage 1 and Stage 2 Trials
GALDERISI A, CUTHBERTSON D, PETRELLI A, MORAN A, SOSENKO J, JACOBSEN L, LIBMAN I, REDONDO M, ISMAIL H. 719-P: Oral Disposition Index (oDI) as an Outcome Measure in Type 1 Diabetes (T1D) Clinical Trials—Evidence from Stage 1 and Stage 2 Trials. Diabetes 2025, 74 DOI: 10.2337/db25-719-p.Peer-Reviewed Original ResearchOral disposition indexC-peptide indexAUC C-peptideC-peptideMarkers of treatment effectivenessStage 1B cell functionYear of treatmentC-peptide measurementsType 1 diabetesPlacebo armMeasure of B-cell functionStage 2T1D prevention trialsTreatment responseTreated armClinical trialsDisposition indexSensitive markerPrevention trialsMetabolic endpointsLong-term effectsInsulin secretionOutcome measuresTeplizumabInternational phase II randomized placebo-controlled study investigating the combination of YIV-906 plus sorafenib (SORA) in HBV (+) patients (Pts) with advanced hepatocellular carcinoma.
Abou-Alfa G, Yen Y, Harding J, Whang-Peng J, Shi Y, Yuen M, Li X, Gu S, Liu C, Jeng L, Yen C, Pan C, Chen S, Hsieh J, Saif M, Liu S, Li F, Lam W, Chu E, Cheng Y. International phase II randomized placebo-controlled study investigating the combination of YIV-906 plus sorafenib (SORA) in HBV (+) patients (Pts) with advanced hepatocellular carcinoma. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.e16244.Peer-Reviewed Original ResearchProgression-free survivalPer-protocol setPlacebo armYIV-906Child-Pugh A liver functionMulti-targeted tyrosine kinase inhibitorRandomized phase 2 studyTumor rejection in vivoRandomized placebo-controlled studyRisk of disease progressionTumor microenvironment inflammationAdvanced hepatocellular carcinomaECOG performance statusPlacebo-controlled studyPhase 2 studyTyrosine kinase inhibitorsRejection in vivoCohort of patientsPotential clinical benefitCTCAE versionTolerated sorafenibSorafenib monotherapyDouble-blindPlacebo-ControlledITT groupLenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous Non–Small-Cell Lung Cancer: Phase 3 LEAP-006 Study
Herbst R, Cho B, Zhou C, Burotto M, Dols M, Sendur M, Moiseyenko V, Casarini I, Nishio M, Hui R, Pons-Tostivint E, Dudnik J, Ahmed S, Okpara C, Dutcus C, Yin L, Luo Y, Chirovsky D, Bhagwati N, Abreu D. Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous Non–Small-Cell Lung Cancer: Phase 3 LEAP-006 Study. Journal Of Thoracic Oncology 2025 PMID: 40419140, DOI: 10.1016/j.jtho.2025.05.016.Peer-Reviewed Original ResearchNonsquamous non-small-cell lung cancerProgression-free survivalMetastatic nonsquamous non-small-cell lung cancerNonsquamous NSCLCNon-small-cell lung cancerFirst-line pembrolizumabOverall survivalTargetable genetic alterationsPlacebo armGenetic alterationsLung cancerTreatment-related adverse eventsFirst-line therapyMedian Follow-UpDouble-blind studyPrimary endpointPembrolizumabLenvatinibAdverse eventsChemotherapyFollow-upDisease progressionSafety signalsPemetrexedMonthsA Machine Learning Approach to Predict Cognitive Decline in Alzheimer Disease Clinical Trials
Nallapu B, Petersen K, Qian T, Demirsoy I, Ghanbarian E, Davatzikos C, Lipton R, Ezzati A, Weiner M, Aisen P, Petersen R, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Landau S, Rivera-Mindt M, Okonkwo O, Shaw L, Lee E, Toga A, Beckett L, Harvey D, Green R, Saykin A, Nho K, Perrin R, Tosun D, Sachdev P, Green R, Drake E, Montine T, Conti C, Weiner M, Nosheny R, Sacrey D, Fockler J, Miller M, Conti C, Kwang W, Jin C, Diaz A, Ashford M, Flenniken D, Kormos A, Petersen R, Aisen P, Rafii M, Raman R, Jimenez G, Donohue M, Salazar J, Fidell A, Boatwright V, Robison J, Zimmerman C, Cabrera Y, Walter S, Clanton T, Shaffer E, Webb C, Hergesheimer L, Smith S, Ogwang S, Adegoke O, Mahboubi P, Pizzola J, Jenkins C, Beckett L, Harvey D, Donohue M, Saito N, Diaz A, Hussen K, Okonkwo O, Rivera-Mindt M, Amaza H, Thao M, Parkins S, Ayo O, Glittenberg M, Hoang I, Germano K, Strong J, Weisensel T, Magana F, Thomas L, Guzman V, Ajayi A, Di Benedetto J, Talavera S, Jack C, Felmlee J, Fox N, Thompson P, DeCarli C, Forghanian-Arani A, Borowski B, Reyes C, Hedberg C, Ward C, Schwarz C, Reyes D, Gunter J, Moore-Weiss J, Kantarci K, Matoush L, Senjem M, Vemuri P, Reid R, Malone I, Thomopoulos S, Nir T, Jahanshad N, Knaack A, Fletcher E, Harvey D, Tosun-Turgut D, Chen S, Choe M, Crawford K, Yushkevich P, Das S, Jagust W, Landau S, Koeppe R, Rabinovici G, Villemagne V, LoPresti B, Perrin R, Morris J, Franklin E, Bernhardt H, Cairns N, Taylor-Reinwald L, Shaw L, Lee E, Lee V, Korecka M, Brylska M, Wan Y, Trojanowki J, Toga A, Crawford K, Neu S, Saykin A, Nho K, Foroud T, Jo T, Risacher S, Craft H, Apostolova L, Nudelman K, Faber K, Potter Z, Lacy K, Kaddurah-Daouk R, Shen L, Karlawish J, Erickson C, Grill J, Largent E, Harkins K, Weiner M, Thal L, Kachaturian Z, Frank R, Snyder P, Buckholtz N, Hsiao J, Ryan L, Molchan S, Khachaturian Z, Carrillo M, Potter W, Barnes L, Bernard M, González H, Ho C, Hsiao J, Jackson J, Masliah E, Masterman D, Okonkwo O, Perrin R, Ryan L, Silverberg N, Silbert L, Kaye J, White Salazar S, Pierce A, Thomas A, Clay T, Schwartz D, Devereux G, Taylor J, Ryan J, Nguyen M, DeCapo M, Shang Y, Schneider L, Munoz C, Ferman D, Conant C, Martin K, Oleary K, Pawluczyk S, Trejo E, Dagerman K, Teodoro L, Becerra M, Fairooz M, Garrison S, Boudreau J, Avila Y, Brewer J, Jacobson A, Gama A, Kim C, Little E, Frascino J, Ferng N, Trujillo S, Heidebrink J, Koeppe R, MacDonald S, Malyarenko D, Ziolkowski J, O'Connor J, Robert N, Lowe S, Rogers V, Petersen R, Hackenmiller B, Boeve B, Kreuger C, Jones D, Knopman D, Botha H, Magnuson J, Graff-Radford J, Crawley K, Schumacher M, McKinzie S, Smith S, Helland T, Lowe V, Ramanan V, Pavlik V, Faircloth J, Bishop J, Nath J, Chaudhary M, Kataki M, Yu M, Pacini N, Barker R, Brooks R, Aggarwal R, Honig L, Stern Y, Mintz A, Cordona J, Hernandez M, Long J, Arnold A, Groves A, Middleton A, Vogler B, McCurry C, Mayo C, Raji C, Amtashar F, Klemp H, Elmore H, Ruszkiewicz J, Kusuran J, Stewart J, Horenkamp J, Greeson J, Wever K, Vo K, Larkin K, Rao L, Schoolcraft L, Gallagher L, Paczynski M, McMillan M, Holt M, Gagliano N, Henson R, LaBarge R, Swarm R, Munie S, Cepeda S, Winterton S, Hegedus S, Wilson T, Harte T, Bonacorsi Z, Geldmacher D, Watkins A, Barger B, Smelser B, Bates C, Stover C, McKinley E, Ikner G, Hendrix H, Cooper H, Mahaffey J, Robbins L, Ashley L, Natelson-Love M, Carter P, Solomon V, Grossman H, Groome A, Ardolino A, Kaplan A, Sheppard F, Burgos-Rivera G, Garcia-Camilo G, Lim J, Neugroschl J, Jackson K, Evans K, Soleimani L, Sano M, Ghesani N, Binder S, Apuango X, Sood A, Troutman A, Blanchard K, Richards A, Nelson G, Hendrickson K, Yurko E, Plenge J, Rufo V, Shah R, Duara R, Lynch B, Chirinos C, Dittrich C, Campbell D, Mejia D, Perez G, Colvee H, Gonzalez J, Gondrez J, Knaack J, Acevedo M, Cereijo M, Greig-Custo M, Villar M, Wishnia M, Detling S, Barker W, Albert M, Moghekar A, Rodzon B, Demsky C, Pontone G, Pekar J, Farrington L, Pomper M, Johnson N, Alo T, Sadowski M, Ulysse A, Masurkar A, Marti B, Mossa D, Geesey E, Petrocca E, Schulze E, Wong J, Boonsiri J, Kenowsky S, Martinez T, Briglall V, Doraiswamy P, Nwosu A, Adhikari A, Hellegers C, Petrella J, James O, Wong T, Hawk T, Vaishnavi S, McCoubrey H, Nasrallah I, Rovere R, Maneval J, Robinson E, Rivera F, Uffelman J, Combs M, O'Donnell P, Manning S, King R, Nieto A, Glueck A, Mandal A, Swain A, Gamble B, Meacham B, Forenback D, Ross D, Cheatham E, Hartman E, Cornell G, Harp J, Ashe L, Goins L, Watts L, Yazell M, Mandal P, Buckler R, Vincent S, Rudd T, Lopez O, Malia A, Chiado C, Zik C, Ruszkiewicz J, Savage K, Fenice L, Oakley M, Tacey P, Berman S, Bowser S, Hegedus S, Saganis X, Porsteinsson A, Mathewson A, Widman A, Holvey B, Clark E, Morales E, Young I, Ruszkiewicz J, Hopkins K, Martin K, Kowalski N, Hunt R, Calzavara R, Kurvach R, D'Ambrosio S, Thai G, Vides B, Lieb B, McAdams-Ortiz C, Toso C, Mares I, Moorlach K, Liu L, Corona M, Nguyen M, Tallakson M, McDonnell M, Rangel M, Basheer N, Place P, Romero R, Tam S, Nguyen T, Thomas A, Frolov A, Khera A, Browning A, Kelley B, Dawson C, Mathews D, Most E, Phillips E, Nguyen L, Nunez M, Miller M, Jones M, Martinez N, Logan R, McColl R, Pham S, Fox T, Moore T, Levey A, Brown A, Kippels A, Ellison A, Lyons C, Hales C, Parry C, Williams C, McCorkle E, Harris G, Rose H, Jooma I, Al-Amin J, Lah J, Webster J, Swiniarski J, Chapman L, Donnelly L, Mariotti L, Locke M, Vaughn P, Penn R, Carpentier S, Yeboah S, Basadre S, Malakauskas S, Lyron S, Villinger T, Burney T, Burns J, Abusalim A, Dahlgren A, Montero A, Arthur A, Dooly H, Kreszyn K, Berner K, Gillen L, Scanlan M, Madison M, Mathis N, Switzer P, Townley R, Fikru S, Sullivan S, Wright E, Beigi M, Daley A, Ko A, Luong B, Nyborg G, Morales J, Durbin K, Garcia L, Parand L, Macias L, Monserratt L, Farchi M, Wu P, Hernandez R, Rodriguez T, Graff-Radford N, Marolt A, Thomas A, Aloszka D, Moncayo E, Westerhold E, Day G, Chrestensen K, Imhansiemhonehi M, McKinzie S, Stephens S, Grant S, Brosch J, Perkins A, Saunders A, Kovac D, Polson H, Mwaura I, Mejia K, Britt K, King K, Nichols K, Lawrence K, RankinW L, Farlow M, Wiesenauer P, Bryant R, Herring S, Lynch S, Wilson S, Day T, Korst W, van Dyck C, Mecca A, Miller A, Brennan A, Khan A, Ruan A, Gunnoud C, Mendonca C, Raynes-Goldfinger D, Salardini E, Hidalgo E, Cooper E, Singh E, Murphy E, May J, Stanhope J, Lam J, Waszak J, Nelsen K, Sacaza K, Hasbani M, Donahue M, Chen M, Barcelos N, Eigenberger P, Bonomi R, O'Dell R, Jefferson S, Khasnavis S, Smilowitz S, DeStefano S, Good S, Camarro T, Clayton V, Cavrel Y, Lu Y, Chertkow H, Bergman H, Hosein C, Black S, Kapadia A, Bhan A, Lam B, Scottc C, Gabriel G, Bray J, Zotovic L, Gutierrez M, Masellis M, Farshadi M, Gui M, Mitchellc M, Taylor R, Endre R, Taghi-Zada Z, Hsiung R, English C, Kim E, Yau E, Tong H, Barlow L, Jennings L, Assaly M, Nunes P, Marian T, Kertesz A, Rogers J, Trost D, Wint D, Bernick C, Munic D, Grant I, Korkoyah A, Raja A, Lapins A, Ryan C, Pejic J, Basham K, Lukose L, Haddad L, Quinlan L, Houghtaling N, Sadowsky C, Martinez W, Villena T, Reynolds B, Forero A, Ward C, Brennan E, Figueroa E, Esposito G, Mallory J, Johnson K, Turner K, Seidenberg K, McCann K, Bassett M, Chadwick M, Turner R, Bean R, Sharma S, Marshall G, Haviari A, Pietras A, Wallace B, Munro C, Rivera-Delpin G, Hustead H, Levesque I, Ramirez J, Nolan K, Glennon K, Palou M, Erkkinen M, DaSilva N, Friedman P, Silver R, Salazar R, Polleys R, McGinnis S, Gale S, Hall T, Luu T, Chao S, Lin E, Coleman J, Epperson K, Vasanawala M, Atri A, Rangel A, Evans B, Monarrez C, Cline C, Liebsack C, Bandy D, Goldfarb D, Intorcia D, Olgin J, Clark K, King K, York K, Reade M, Callan M, Glass M, Johnson M, Gutierrez M, Goddard M, Trncic N, Choudhury P, Reyes P, Lowery S, Hall S, Olgin S, de Santiago S, Alosco M, Ton A, Jimenez A, Ellison A, Tran A, Anderson B, Carter D, Veronelli D, Lenio S, Steinberg E, Mez J, Weller J, Johns J, Mez J, Harkins J, Puleio A, Hoti I, Mwicigi J, Puleio A, Alosco M, Schultz O, Lauture M, Steinberg E, Denis R, Killiany R, Singh S, Lenio S, Qiu W, Devis Y, Obisesan T, Stone A, Ordor D, Udodong I, Okonkwo I, Khan J, Turner J, Hughes K, Kadiri O, Duffy C, Moss A, Stapleton K, Toth M, Sanders M, Ayres M, Hamski M, Fatica P, Ogrocki P, Ash S, Pot S, Chen D, Soto A, Tanase C, Bissig D, Vanya H, Russell H, Patel H, Zhang H, Wallace K, Ayers K, Gallegos M, Forloines M, Sinn M, Kahulugan Q, Isip R, Calderon S, Hamm T, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Perrin A, Tariot P, Fleisher A, Reeder S, Capote H, Emborsky A, Mattle A, Ajtai B, Wagner B, Myers B, Slazyk D, Fragale D, Fransen E, Macnamara H, Falletta J, Hirtreiter J, Mechtler L, King M, Asbach M, Rainka M, Zawislak R, Wisniewski S, O'Malley S, Jimenez-Knight T, Peehler T, Aladeen T, Bates V, Wenner V, Elmalik W, Scharre D, Ramamurthy A, Bouchachi S, Kataki M, Tarawneh R, Kelley B, Celmins D, Leader A, Figueroa C, Bauerle H, Patterson K, Reposa M, Presto S, Ahmed T, Stewart W, Pearlson G, Blank K, Anderson K, Santulli R, Schwartz E, Williamson J, Jessup A, Williams A, Duncan C, O'Connell A, Gagnon K, Zamora E, Bateman J, Crawford F, Thompson D, Walker E, Rowell J, White M, Ledford P, Bohlman S, Henkle S, Bottoms J, Moretz L, Hoover B, Shannon M, Rogers S, Baker W, Harrison W, Wu C, DeMarco A, Stipanovich A, Arcuri D, Clark J, Davis J, Doyon K, Amoyaw M, Acosta M, Bailey R, Warren S, Fogerty T, Sanborn V, Hospital B, Riddle M, Salloway S, Malloy P, Correia S, Windon C, Blackburn M, Rosen H, Miller B, Smith A, Mba I, Echevarria J, Janavs J, Roglaski E, Yong M, Devine R, Okhravi H, Rivera E, Kalowsky T, Smith C, Rosario C, Masdeu J, Le R, Gurung M, Sabbagh M, Garcia A, Slaughter M, Elayan N, Acothley S, Pomara N, Hernando R, Pomara V, Reichert C, Brawman-Mintzer O, Acree A, Williams A, Long C, Long R, Newhouse P, Hill S, Boegel A, Seshadri S, Saklad A, Jones F, Hu W, Sotelo V, Rojas Y, Mintzer J, Longmire C, Spicer K. A Machine Learning Approach to Predict Cognitive Decline in Alzheimer Disease Clinical Trials. Neurology 2025, 104: e213490. PMID: 40132145, DOI: 10.1212/wnl.0000000000213490.Peer-Reviewed Original ResearchConceptsClinically meaningful cognitive declineAlzheimer's Disease Neuroimaging InitiativeCognitive declineAD clinical trialsAlzheimer's Disease Neuroimaging Initiative participantsBase prevalencePredicting cognitive declineAlzheimer's diseaseNeuropsychological testsPlacebo armValidation sampleAlzheimer's disease clinical trialsIndependent validation samplePositive predictive valueDetect treatment effectsTreatment trialsVolumetric MRIPlacebo treatmentMild dementiaAmyloid burdenAD trialsInternal validation sampleParticipantsTreatment effectsAPOE genotype
2024
BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Longlax S, Koster K, Kamat A, Lozano M, Lerner S, Hannigan R, Nishiguchi T, Abhimanyu, Sheikh D, Ladki M, Portillo A, Koirala A, Patel T, Spieler Z, Benjamin A, Lebedev M, Ofili T, Hutchison R, Udeani G, Opperman L, Neal G, Mandalakas A, Netea M, Arditi M, Avalos P, Grimm S, Coarfa C, Cirillo J, DiNardo A. BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Open Forum Infectious Diseases 2024, 12: ofaf007. PMID: 39872813, PMCID: PMC11770274, DOI: 10.1093/ofid/ofaf007.Peer-Reviewed Original ResearchVaccine immunityDNA methylation changesBCG-induced trained immunityClinical trialsBCG vaccinationPlacebo-controlled clinical trialStudy enrollmentAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 infectionCovid-19 specific vaccineMethylation changesCoronavirus 2 infectionCOVID-19 vaccine immunitySymptomatic COVID-19Secondary analysisSARS-CoV-2 antigensInnate immune responseDouble-blindPlacebo armBCG TiceTrained immunitySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Coronavirus immunityRespiratory syndrome coronavirus 2A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection
Drekonja D, Shaukat A, Huang Y, Zhang J, Reinink A, Nugent S, Dominitz J, Davis-Karim A, Gerding D, Kyriakides T. A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection. Clinical Infectious Diseases 2024, 80: 52-60. PMID: 39271107, DOI: 10.1093/cid/ciae467.Peer-Reviewed Original ResearchCDI recurrenceClostridioides difficile infectionFecal microbiota transplantationRecurrent Clostridioides difficile infectionAdverse eventsPreventing recurrent Clostridioides difficile infectionOral fecal microbiota transplantationMicrobiota transplantationCause of healthcare-associated infectionsSafety of fecal microbiota transplantationDouble-blind clinical trialTrials of efficacyHealthcare-Associated InfectionsStatistically significant differenceRandomized Controlled TrialsClinical recurrenceUnformed stoolsPlacebo armPlacebo capsulesPrimary endpointDifficile infectionRecurrent diarrheaAntibiotic treatmentVeterans Health Administration systemClinical trialsCOBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls
Kowdley K, Hirschfield G, Coombs C, Malecha E, Bessonova L, Li J, Rathnayaka N, Mells G, Jones D, Trivedi P, Hansen B, Smith R, Wason J, Hiu S, Kareithi D, Mason A, Bowlus C, Muller K, Carbone M, Berenguer M, Milkiewicz P, Adekunle F, Villamil A. COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls. The American Journal Of Gastroenterology 2024, 120: 390-400. PMID: 39140490, PMCID: PMC11774195, DOI: 10.14309/ajg.0000000000003029.Peer-Reviewed Original ResearchPrimary biliary cholangitisObeticholic acidClinical outcomesFunctional unblindingPlacebo armBiliary cholangitisConfirmatory trialsUS healthcare claims databasePrimary biliary cholangitis patientsOCA therapyObeticholic acid treatmentPrimary composite endpointAs-treated analysisHealthcare claims databaseNegative clinical outcomesUncontrolled ascitesPlacebo patientsHepatic decompensationPrimary endpointLiver transplantationComposite endpointCommercial therapySafety signalsPlaceboTreatment crossover1896-LB: Clinical Features and C-Peptide Levels Associated with Diabetic Ketoacidosis in Patients with Type 2 Diabetes on Dapagliflozin vs. Placebo—Insights from DECLARE-TIMI 58
MI KANG Y, MELLONI G, CAHN A, RAZ I, MOURA F, BHATT D, INZUCCHI S, LEITER L, MCGUIRE D, WILDING J, GAUSE-NILSSON I, OSCARSSON J, MARSTON N, RUFF C, SABATINE M, WIVIOTT S. 1896-LB: Clinical Features and C-Peptide Levels Associated with Diabetic Ketoacidosis in Patients with Type 2 Diabetes on Dapagliflozin vs. Placebo—Insights from DECLARE-TIMI 58. Diabetes 2024, 73 DOI: 10.2337/db24-1896-lb.Peer-Reviewed Original ResearchDuke Clinical Research InstituteC-pepClinical Research InstituteDKA eventsC-peptideLower fasting C-peptideMedian Follow-UpRandomized to dapagliflozinFasting C-peptideDuration of T2DC-peptide testingRisk of DKACV outcome trialsAmerican College of CardiologyAbsolute risk differenceRate of DKAImpaired insulin secretionType 2 diabetesPlacebo armClinical featuresPopulation Health Research InstituteCSL BehringDiabetic ketoacidosisFerring PharmaceuticalsOutcome trialsHow many patients do you need? Investigating trial designs for anti‐seizure treatment in acute brain injury patients
Parikh H, Sun H, Amerineni R, Rosenthal E, Volfovsky A, Rudin C, Westover M, Zafar S. How many patients do you need? Investigating trial designs for anti‐seizure treatment in acute brain injury patients. Annals Of Clinical And Translational Neurology 2024, 11: 1681-1690. PMID: 38867375, PMCID: PMC11251465, DOI: 10.1002/acn3.52059.Peer-Reviewed Original ResearchConceptsRandomized Controlled TrialsAnti-seizure treatmentAcute brain injuryEpileptiform activityBrain injuryTreatment armsModel treatment responsePlacebo-controlled trialAcute brain injury patientsSingle-center cohortDrug efficacy dataBrain injury patientsCohort of adultsDischarge modified Rankin ScaleFeasibility of randomized controlled trialsSample sizePlacebo armTreatment responseDrug doseEA trajectoriesEfficacy dataWorsen outcomesRankin ScaleDrug efficacyPlaceboAdjuvant Everolimus in Patients with Completely Resected, Very High-risk Renal Cell Carcinoma of Clear Cell Histology: Results from the Phase 3 Placebo-controlled SWOG S0931 (EVEREST) Trial
Lara P, Tangen C, Heath E, Gulati S, Stein M, Meng M, Alva A, Pal S, Puzanov I, Clark J, Choueiri T, Agarwal N, Uzzo R, Haas N, Synold T, Plets M, Vaishampayan U, Shuch B, Lerner S, Thompson I, Ryan C. Adjuvant Everolimus in Patients with Completely Resected, Very High-risk Renal Cell Carcinoma of Clear Cell Histology: Results from the Phase 3 Placebo-controlled SWOG S0931 (EVEREST) Trial. European Urology 2024, 86: 258-264. PMID: 38811313, PMCID: PMC12036081, DOI: 10.1016/j.eururo.2024.05.012.Peer-Reviewed Original ResearchRecurrence-free survivalHigh-risk diseaseRenal cell cancerPhase 3 trialOverall survivalEverolimus armCell histologyPlacebo armDiscontinuation rate due to adverse eventsHigh-risk renal cell carcinomaCompare recurrence-free survivalPatients treated with everolimusPositive phase 3 trialClear cell renal cell cancerCell renal cell cancerRate of side effectsClear cell histologyComparison to placeboComplete surgical removalNode-positive statusRisk of recurrenceRisk stratification toolCox regression modelsAdjuvant sunitinibAdjuvant trialsProtocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam)
Feldman H, Luchsinger J, Léger G, Taylor C, Jacobs D, Salmon D, Edland S, Messer K, Revta C, Flowers S, Jones K, Koulman A, Yarasheski K, Verghese P, Venkatesh V, Zetterberg H, Durant J, Lupo J, Gibson G, Group F. Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam). PLOS ONE 2024, 19: e0302998. PMID: 38809849, PMCID: PMC11135745, DOI: 10.1371/journal.pone.0302998.Peer-Reviewed Original ResearchConceptsPhase 2bPhase 2aRandomized double-blind placebo-controlled trialDouble-blind placebo-controlled trialCo-primary efficacy endpointsTolerability eventsBest-tolerated dosePlacebo-controlled trialWell-tolerated dosesAlzheimer's diseaseLonger-term safetyEfficacy of drug deliveryWeeks of treatmentTargeted therapeutic approachesErythrocyte transketolase activityGroups of participantsDouble-blindPlacebo armEfficacy endpointSecondary endpointsOral treatmentPharmacokinetic measurementsClinical trialsTherapeutic approachesBlood markersResults of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder
Hoebeke P, Hittelman A, Jenkins B, Geib T, Titanji W, Bogaert G. Results of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder. Journal Of Pediatric Urology 2024, 20: 600.e1-600.e8. PMID: 38906707, DOI: 10.1016/j.jpurol.2024.04.019.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsOveractive bladderPediatric patientsUrinary retentionUI episodesPrimary endpointTreatment of overactive bladderResponse rateUrinary incontinence (UIFrequency of UI episodesMultiple-dose studyNumerically greater reductionsLack of approved treatmentsTreatment cycles 1Urinary tract infectionBaseline to weekTreat overactive bladderTreatment response ratesTreatment cycle 2Dose armAnticholinergic therapyDouble-blindPlacebo armOnabotulinumtoxinA injectionsTract infections
2023
A Phase 2a proof‐of‐concept double‐blind, randomized, placebo‐controlled trial of nicotinamide in early Alzheimer’s disease
Grill J, Tam S, Thai G, Pierce A, Green K, Gillen D, Teng E, Kremen S, Beigi M, Rissman R, Leger G, Zhang J, Jin S, Messer K, Feldman H. A Phase 2a proof‐of‐concept double‐blind, randomized, placebo‐controlled trial of nicotinamide in early Alzheimer’s disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.077979.Peer-Reviewed Original ResearchPhase 2a proofP-Tau 181Placebo armTotal tauCDR-SBEarly ADAmyloid beta 40Placebo-controlled trialCerebrospinal fluid levelsEarly Alzheimer's diseaseAlzheimer's disease biomarkersDisease biomarkersPhosphorylation of tauClass III histoneSecondary outcomesAdverse eventsClinical characteristicsPrimary outcomeADCS-ADLStudy armsTreatment initiationCSF biomarkersADAS-Cog13Biomarker outcomesMean changeEffect of Doxycycline on Progression of Arterial Calcification in the Noninvasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT)
Kim T, Kostiuk V, Olson S, Curci J, Matsumura J, Baxter B, Blackwelder W, Terrin M, Guzman R. Effect of Doxycycline on Progression of Arterial Calcification in the Noninvasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT). Annals Of Vascular Surgery 2023, 104: 1-9. PMID: 37356652, PMCID: PMC10748791, DOI: 10.1016/j.avsg.2023.06.019.Peer-Reviewed Original ResearchAbdominal Aortic Aneurysm Clinical TrialSerum MMP-3MMP-9 levelsArterial calcificationEffect of doxycyclineNon-invasive treatmentMMP-3Clinical trialsTomography scanMatrix metalloproteinasesSmall aortic aneurysmsArtery calcificationBaseline characteristicsPlacebo armCalcium scoreStudy armsAortic aneurysmPreclinical modelsMean changeAbdominal vesselsPatientsIndividual arteriesMatrix degradingDoxycyclineCalcificationEffects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS)
Shitara K, George B, Taieb J, Sundar R, Fakih M, Makris L, Benhadji K, Ghidini M. Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS). Journal Of Cancer Research And Clinical Oncology 2023, 149: 9361-9374. PMID: 37213030, PMCID: PMC10374776, DOI: 10.1007/s00432-023-04813-z.Peer-Reviewed Original ResearchConceptsProgression-free survivalGastric/gastroesophageal junction cancerJunction cancerSurvival benefitSafety profileEastern Cooperative Oncology Group performance statusRandomized phase III trialAssociated with survival benefitMedian overall survivalPhase III trialsPost hoc exploratory analysisLater-lineTrifluridine/tipiracil treatmentHematologic toxicityPrior therapyMedian overallOverall survivalIII trialsPlacebo armPerformance statusResultsBaseline characteristicsMedian timeRamucirumabTherapy patternsClinical trialsLongitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease
Chen C, McCullough A, Gordon B, Joseph-Mathurin N, Flores S, McKay N, Hobbs D, Hornbeck R, Fagan A, Cruchaga C, Goate A, Perrin R, Wang G, Li Y, Shi X, Xiong C, Pontecorvo M, Klein G, Su Y, Klunk W, Jack C, Koeppe R, Snider B, Berman S, Roberson E, Brosch J, Surti G, Jiménez-Velázquez I, Galasko D, Honig L, Brooks W, Clarnette R, Wallon D, Dubois B, Pariente J, Pasquier F, Sanchez-Valle R, Shcherbinin S, Higgins I, Tunali I, Masters C, van Dyck C, Masellis M, Hsiung R, Gauthier S, Salloway S, Clifford D, Mills S, Supnet-Bell C, McDade E, Bateman R, Benzinger T. Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2669-2682. PMID: 37017737, PMCID: PMC10330155, DOI: 10.1007/s00259-023-06209-0.Peer-Reviewed Original ResearchConceptsStandardized uptake value ratioPhase 2/3 clinical trialsPositron emission tomographyAnti-Aβ monoclonal antibodyClinical trialsPlacebo armDrug effectsLongitudinal changesMonoclonal antibodiesGlobal cortical standardized uptake value ratioHead comparisonCortical standardized uptake value ratioRegional standardized uptake value ratiosAβ positron emission tomographyAmyloid-β positron emission tomographyAlzheimer's disease clinical trialsPET imagingUptake value ratioAβ PET imagingSimulated clinical trialTwo-sample t-testDrug armPittsburgh CompoundPET scansWelch two sample t-test
2022
Asthma exacerbations during the pandemic: Time to rethink clinical markers
Ortega H, Katz L, Chupp G. Asthma exacerbations during the pandemic: Time to rethink clinical markers. Journal Of Allergy And Clinical Immunology Global 2022, 2: 97-100. PMID: 36281240, PMCID: PMC9581642, DOI: 10.1016/j.jacig.2022.09.003.Peer-Reviewed Original ResearchPrimary end pointAsthma exacerbationsClinical studiesClinical markersEnd pointCOVID-19 pandemicClinical trial enrollmentCoronavirus disease 2019 (COVID-19) pandemicNitric oxide levelsRecent clinical reportsDisease 2019 pandemicPrior exacerbationsPlacebo armFuture exacerbationsTrial enrollmentClinical trialsOxide levelsExacerbationClinical reportsClinical practiceCOVID-19Prior yearPandemicEnrollmentBest predictorLong-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial.
Fenaux P, Santini V, Komrokji R, Zeidan A, Garcia-Manero G, Buckstein R, Miteva D, Keeperman K, Holot N, Zhang J, Hughes C, Rosettani B, Yucel A, Platzbecker U. Long-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial. Journal Of Clinical Oncology 2022, 40: 7056-7056. DOI: 10.1200/jco.2022.40.16_suppl.7056.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesAcute myeloid leukemiaErythropoiesis-stimulating agentsMedian cumulative durationCumulative durationRBC-TIMedian durationPlacebo armAML progressionRegular red blood cell transfusionsRed blood cell transfusionRBC transfusion independenceBlood cell transfusionHigh-risk MDSKaplan-Meier analysisLong-term followRate of progressionLong-term clinical valueEligible ptsCell transfusionPrimary endpointDurable responsesTransfusion independenceAML diagnosisDose escalationAlzheimer disease neuropathology in a patient previously treated with aducanumab
Plowey ED, Bussiere T, Rajagovindan R, Sebalusky J, Hamann S, von Hehn C, Castrillo-Viguera C, Sandrock A, Budd Haeberlein S, van Dyck CH, Huttner A. Alzheimer disease neuropathology in a patient previously treated with aducanumab. Acta Neuropathologica 2022, 144: 143-153. PMID: 35581440, PMCID: PMC9217863, DOI: 10.1007/s00401-022-02433-4.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesLong-term extensionStandard uptake value ratioAlzheimer's diseaseAmyloid positron emission tomographyBraak stage VPhase 1b studyPhospho-tau immunohistochemistryPostmortem neuropathologic examinationSpecies of AβAD neuropathologic changeFirst autopsy reportAlzheimer's disease neuropathologyUptake value ratioAmyloid PET scanMild Alzheimer's diseasePositron emission tomographyLast doseReactive microgliaNeuropathologic evidenceNeuropathologic examinationPlacebo armImaging abnormalitiesMonthly dosesNeuropathologic changesSelinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial
Gounder MM, Razak AA, Somaiah N, Chawla S, Martin-Broto J, Grignani G, Schuetze SM, Vincenzi B, Wagner AJ, Chmielowski B, Jones RL, Riedel RF, Stacchiotti S, Loggers ET, Ganjoo KN, Le Cesne A, Italiano A, del Muro X, Burgess M, Piperno-Neumann S, Ryan C, Mulcahy MF, Forscher C, Penel N, Okuno S, Elias A, Hartner L, Philip T, Alcindor T, Kasper B, Reichardt P, Lapeire L, Blay JY, Chevreau C, Morales C, Schwartz GK, Chen JL, Deshpande H, Davis EJ, Nicholas G, Gröschel S, Hatcher H, Duffaud F, Herráez AC, Beveridge RD, Badalamenti G, Eriksson M, Meyer C, von Mehren M, Van Tine BA, Götze K, Mazzeo F, Yakobson A, Zick A, Lee A, Gonzalez AE, Napolitano A, Dickson MA, Michel D, Meng C, Li L, Liu J, Ben-Shahar O, Van Domelen DR, Walker CJ, Chang H, Landesman Y, Shah JJ, Shacham S, Kauffman MG, Attia S. Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial. Journal Of Clinical Oncology 2022, 40: 2479-2490. PMID: 35394800, PMCID: PMC9467680, DOI: 10.1200/jco.21.01829.Peer-Reviewed Original ResearchConceptsProgression-free survivalDedifferentiated liposarcomaNext treatmentCommon treatment-emergent adverse eventsPatients age 12 yearsTreatment-emergent adverse eventsLonger progression-free survivalPlacebo-controlled studyPrimary end pointLines of therapyAge 12 yearsAdverse eventsOverall survivalPlacebo armSupportive careClinical benefitStudy treatmentPredictive biomarkersPreclinical modelsProspective validationGrade 3Dose reductionPlaceboSide effectsPatients
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