2024
Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma
Foss F, Kim Y, Prince H, Akilov O, Querfeld C, Seminario-Vidal L, Fisher D, Kuzel T, Yannakou C, Geskin L, Feldman T, Sokol L, Allen P, Dang N, Cabanillas F, Wong H, Ooi C, Xing D, Sauter N, Singh P, Czuczman M, Duvic M. Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma. Journal Of Clinical Oncology 2024, 43: 1198-1209. PMID: 39700456, PMCID: PMC11949209, DOI: 10.1200/jco-24-01549.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaTreatment-emergent adverse eventsTime to responseT-cell lymphomaTumor burdenRefractory cutaneous T-cell lymphomaEnd pointsEfficacy end pointCapillary leak syndromePrimary efficacy analysisSecondary end pointsHuman interleukin-2Unmet medical needMedian DoRSystemic therapyInfusion reactionsOpen-labelDenileukin diftitoxEfficacy analysisAdverse eventsInterleukin-2Safety resultsQ1-Q3PatientsResponse rateMobile Stroke Unit Management in Patients With Acute Ischemic Stroke Eligible for Intravenous Thrombolysis
Mac Grory B, Sun J, Alhanti B, Lusk J, Li F, Adeoye O, Furie K, Hasan D, Messe S, Sheth K, Schwamm L, Smith E, Bhatt D, Fonarow G, Saver J, Xian Y, Grotta J. Mobile Stroke Unit Management in Patients With Acute Ischemic Stroke Eligible for Intravenous Thrombolysis. JAMA Neurology 2024, 81: 1250-1262. PMID: 39466286, PMCID: PMC11581552, DOI: 10.1001/jamaneurol.2024.3659.Peer-Reviewed Original ResearchEmergency medical servicesEmergency medical service managementMobile stroke unitPrehospital managementSymptomatic intracranial hemorrhageHospital dischargeGlobal disabilityIn-hospital mortalityEfficacy end pointUtility-weighted modified Rankin scaleStroke unit managementAcute ischemic strokeIschemic strokePrimary analytic cohortDiagnosis of ischemic strokeIntravenous thrombolysisAmerican Heart AssociationEnd pointsGuidelines-StrokeUW-mRSSecondary efficacy end pointsMain OutcomesMedical servicesStroke unitAmbulation statusEfficacy and Safety of Nefecon in Patients with IgA Nephropathy from Mainland China: 2-Year NefIgArd Trial Results
Zhang H, Lafayette R, Wang B, Ying L, Zhu Z, Stone A, Kristensen J, Barratt J. Efficacy and Safety of Nefecon in Patients with IgA Nephropathy from Mainland China: 2-Year NefIgArd Trial Results. Kidney360 2024, 5: 1881-1892. PMID: 39724565, PMCID: PMC11687989, DOI: 10.34067/kid.0000000583.Peer-Reviewed Original ResearchEfficacy end pointImmunoglobulin A nephropathyEnd pointsImmune-mediated kidney diseasesGlobal study populationNo severe infectionsPreservation of eGFRIgAN pathophysiologyPrimary IgANDouble-blindEGFR reductionConsistent with global studiesEfficacy outcomesNo deathsAdverse eventsSevere infectionsChina cohortFollow-upPlaceboKidney diseaseSafety signalsBudesonide formulationIgANSupportive carePatientsConsiderations for the design and conduct of pediatric obesity pharmacotherapy clinical trials: Proceedings of expert roundtable meetings
Kelly A, Bahlke M, Baker J, de Beaufort C, Belin R, Fonseca H, Hale P, Holm J, Hsia D, Jastreboff A, Juliusson P, Murphy M, Pak J, Paul E, Rudolph B, Srivastava G, Tornøe C, Weghuber D, Fox C. Considerations for the design and conduct of pediatric obesity pharmacotherapy clinical trials: Proceedings of expert roundtable meetings. Pediatric Obesity 2024, 19: e13161. PMID: 39289849, DOI: 10.1111/ijpo.13161.Peer-Reviewed Original ResearchAnti-obesity medicationsExcessive weight reductionClinical trialsEnd pointsDown-titrationEligibility criteriaLong-term health outcomesBMI z-scoreActive comparatorEfficacy end pointPlacebo-controlled trialSecondary end pointsRun-in phaseFollow-up periodFollow-up phaseHealth outcomesObesity expertsTrial eligibility criteriaClinical careWeight reductionMultidisciplinary groupClinical trial protocolsPrimary outcomeWeight regainTrial protocolRationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design
Busl K, Smith C, Troxel A, Fava M, Illenberger N, Pop R, Yang W, Frota L, Gao H, Shan G, Hoh B, Maciel C. Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design. Neurocritical Care 2024, 42: 290-300. PMID: 39138719, PMCID: PMC11810580, DOI: 10.1007/s12028-024-02078-z.Peer-Reviewed Original ResearchSequential parallel comparison designDouble-blindPain controlPterygopalatine fossaClinical trialsPlacebo-Controlled Clinical TrialPrimary tolerability end pointEnd pointsVerbal pain scoresEfficacy end pointOpen-label phaseTolerability end pointsPhase III trialsPost-subarachnoid hemorrhagePhase IIIII trialsPain scoresAcute headacheAneurysmal SAHSevere headachePeriprocedural monitoringPost-SAHHeadache phenotypeUltrasound guidanceAwake patientsAlirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia
Santos R, Wiegman A, Caprio S, Cariou B, Averna M, Poulouin Y, Scemama M, Manvelian G, Garon G, Daniels S. Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia. JAMA Pediatrics 2024, 178: 283-293. PMID: 38315470, PMCID: PMC10845038, DOI: 10.1001/jamapediatrics.2023.6477.Peer-Reviewed Original ResearchDouble-blind periodLipid-lowering therapyHeterozygous familial hypercholesterolemiaPediatric patientsLDL-CLipid parametersFamilial hypercholesterolemiaRecommended low-density lipoprotein cholesterolAdjunctive lipid-lowering therapiesSecondary efficacy end pointsEnd pointsPediatric patients aged 8Least-squares mean differenceEfficacy of alirocumabOpen-label periodEfficacy end pointLow-density lipoprotein cholesterolReduced LDL-CBaseline to weekPrimary end pointAdverse event incidencePatients aged 8Randomized clinical trialsSquare mean differencesStatistically significant reduction
2023
Determination and Confirmation of Recommended Ph2 Dose of Amivantamab in Epidermal Growth Factor Receptor Exon 20 Insertion Non‐Small Cell Lung Cancer
Haddish‐Berhane N, Su Y, Russu A, Thayu M, Knoblauch R, Mehta J, Xie J, Gibbs E, Sun Y, Zhou H. Determination and Confirmation of Recommended Ph2 Dose of Amivantamab in Epidermal Growth Factor Receptor Exon 20 Insertion Non‐Small Cell Lung Cancer. Clinical Pharmacology & Therapeutics 2023, 115: 468-477. PMID: 37776107, DOI: 10.1002/cpt.3064.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAdverse events of clinical interestEpidermal growth factor receptor-exonPopPK modelRecommended phase II dosePrimary efficacy end pointEGFR exon 20 insertionsPhase II doseExon 20 insertionsEfficacy end pointCovariates of clearanceVolume of distributionE-R relationshipSerum concentration dataEGFR ex20insII doseExposure-response analysesPlatinum chemotherapyExposure-responseEfficacy analysisPK variabilityPopulation PKAmivantamabStandardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP
Litton J, Regan M, Pusztai L, Rugo H, Tolaney S, Garrett-Mayer E, Amiri-Kordestani L, Basho R, Best A, Boileau J, Denkert C, Foster J, Harbeck N, Jacene H, King T, Mason G, O'Sullivan C, Prowell T, Richardson A, Sepulveda K, Smith M, Tjoe J, Turashvili G, Woodward W, Butler L, Schwartz E, Korde L. Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP. Journal Of Clinical Oncology 2023, 41: 4433-4442. PMID: 37433103, PMCID: PMC10522109, DOI: 10.1200/jco.23.00435.Peer-Reviewed Original ResearchConceptsSecondary end pointsPathologic complete responseClinical trialsEnd pointStandardized definitionsHormone receptor-positive diseaseCurative-intent surgeryNeoadjuvant clinical trialsPathologic nodal evaluationResidual invasive cancerEfficacy end pointReceptor-positive diseaseBreast cancer clinical trialsResidual cancer burdenAlternative end pointsTrial end pointsRegional lymph nodesCancer end pointsCross-trial comparisonsSurvival end pointsEnd point definitionsCancer clinical trialsDrug Administration (FDA) regulatory considerationsEfficacy outcomesComplete responseRandomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Johnson D, Fehrenbacher L, Novotny W, Herbst R, Nemunaitis J, Jablons D, Langer C, DeVore R, Gaudreault J, Damico L, Holmgren E, Kabbinavar F. Randomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer. Journal Of Clinical Oncology 2023, 41: 2305-2312. PMID: 37126944, DOI: 10.1200/jco.22.02543.Peer-Reviewed Original ResearchCell lung cancerSingle-agent bevacizumabLung cancerMajor hemoptysisCell histologyControl armResponse ratePrimary efficacy end pointNonsquamous cell histologyProminent adverse eventSafety of bevacizumabEfficacy end pointDistinct clinical patternsPhase II trialSquamous cell histologyLonger median timeHigh response rateMajor blood vesselsPreviously UntreatedStable diseaseII trialAdverse eventsControl patientsClinical patternMedian timeUS Food and Drug Administration Approval of Drugs Not Meeting Pivotal Trial Primary End Points, 2018-2021
Johnston J, Ross J, Ramachandran R. US Food and Drug Administration Approval of Drugs Not Meeting Pivotal Trial Primary End Points, 2018-2021. JAMA Internal Medicine 2023, 183: 376-380. PMID: 36780148, PMCID: PMC9926353, DOI: 10.1001/jamainternmed.2022.6444.Peer-Reviewed Original Research
2022
Network Meta-Analysis Comparing Angiotensin Receptor-Neprilysin Inhibitors, Angiotensin Receptor Blockers, and Angiotensin-Converting Enzyme Inhibitors in Heart Failure With Reduced Ejection Fraction
Park D, An S, Attanasio S, Jolly N, Malhotra S, Doukky R, Samsky M, Sen S, Ahmad T, Nanna M, Vij A. Network Meta-Analysis Comparing Angiotensin Receptor-Neprilysin Inhibitors, Angiotensin Receptor Blockers, and Angiotensin-Converting Enzyme Inhibitors in Heart Failure With Reduced Ejection Fraction. The American Journal Of Cardiology 2022, 187: 84-92. PMID: 36459752, PMCID: PMC10958453, DOI: 10.1016/j.amjcard.2022.10.026.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBayes TheoremDeathHeart FailureHumansHypotensionNeprilysinNetwork Meta-AnalysisRandomized Controlled Trials as TopicReceptors, AngiotensinStroke VolumeTreatment OutcomeVentricular Dysfunction, LeftConceptsAngiotensin receptor neprilysin inhibitorAngiotensin receptor blockersReduced ejection fractionHeart failureEjection fractionHigh riskCause mortalityReceptor blockersCardiac deathLower riskEnzyme inhibitorsMajor adverse cardiac eventsAngiotensin converting enzyme (ACE) inhibitorsAdverse cardiac eventsEfficacy end pointNetwork meta-analysis approachImproved clinical outcomesRandomized clinical trialsP scoreCardiac eventsAngiotensin receptorsClinical outcomesNeprilysin inhibitorClinical benefitRecent trialsConsistency between trials presented at conferences, their subsequent publications and press releases
Rowhani-Farid A, Hong K, Grewal M, Reynolds J, Zhang A, Wallach J, Ross J. Consistency between trials presented at conferences, their subsequent publications and press releases. BMJ Evidence-Based Medicine 2022, 28: 95-102. PMID: 36357160, PMCID: PMC10086295, DOI: 10.1136/bmjebm-2022-111989.Peer-Reviewed Original ResearchConceptsClinical trialsConference abstractsTrial resultsEndpoint definitionsPrimary efficacy end pointEnd pointEfficacy end pointPrimary efficacy endpointClinical Trials RegistryMedical conferencesMultiple logistic regressionCross-sectional analysisSafety endpointEfficacy endpointPeer-reviewed journalsTrial abstractsTrials RegistryTrial characteristicsConsistency of reportingSample sizePrimary analysisSecondary analysisInternational medical conferencesLogistic regressionStudy designOnce-Weekly Exenatide in Youth With Type 2 Diabetes
Tamborlane WV, Bishai R, Geller D, Shehadeh N, Al-Abdulrazzaq D, Vazquez EM, Karoly E, Troja T, Doehring O, Carter D, Monyak J, Sjöström CD. Once-Weekly Exenatide in Youth With Type 2 Diabetes. Diabetes Care 2022, 45: 1833-1840. PMID: 35679098, PMCID: PMC9346995, DOI: 10.2337/dc21-2275.Peer-Reviewed Original ResearchConceptsType 2 diabetesEfficacy end pointWeekly exenatideAdverse eventsPlacebo groupPrimary efficacy end pointSecondary efficacy end pointsEnd pointMetformin monotherapyTreatment of youthInsulin therapyWeek 24Pediatric patientsWeekly injectionsDaily injectionsGlycated hemoglobinCurrent treatmentExenatideBody weightDiabetesLiraglutideWeeksHemoglobinTreatmentBaselineReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals (GUARD-AF): Rationale and design of the GUARD-AF randomized trial of screening for atrial fibrillation with a 14-day patch-based continuous ECG monitor
Singer DE, Atlas SJ, Go AS, Lopes RD, Lubitz SA, McManus DD, Revkin JH, Mills D, Crosson LA, Lenane JC, Aronson RS. ReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals (GUARD-AF): Rationale and design of the GUARD-AF randomized trial of screening for atrial fibrillation with a 14-day patch-based continuous ECG monitor. American Heart Journal 2022, 249: 76-85. PMID: 35472303, DOI: 10.1016/j.ahj.2022.04.005.Peer-Reviewed Original ResearchConceptsOral anticoagulant therapyEfficacy end pointSafety end pointUndiagnosed atrial fibrillationAtrial fibrillationEnd pointAF screeningLong-term oral anticoagulant therapyIndividuals age 70 yearsRate of strokeProportion of patientsScreen-detected casesNovel coronavirus disease 2019 (COVID-19) pandemicAge 70 yearsParoxysmal atrial fibrillationCoronavirus disease 2019 (COVID-19) pandemicPrimary care practicesTarget sample sizeDisease 2019 pandemicLong-term screeningElectronic health recordsBleeding outcomesScreening armAF burdenUsual careRandomized Trial of Chocolate Touch Compared With Lutonix Drug-Coated Balloon in Femoropopliteal Lesions (Chocolate Touch Study)
Shishehbor MH, Zeller T, Werner M, Brodmann M, Parise H, Holden A, Lichtenberg M, Parikh SA, Kashyap VS, Pietras C, Tirziu D, Ardakani S, Beschorner U, Krishnan P, Niazi KA, Wali AU, Lansky AJ. Randomized Trial of Chocolate Touch Compared With Lutonix Drug-Coated Balloon in Femoropopliteal Lesions (Chocolate Touch Study). Circulation 2022, 145: 1645-1654. PMID: 35377157, DOI: 10.1161/circulationaha.122.059646.Peer-Reviewed Original ResearchConceptsLutonix drug-coated balloonDrug-coated balloonsEnd pointPrimary efficacy end pointPrimary safety end pointIndependent clinical events committeeIschemic rest painPrimary efficacy rateEfficacy end pointPrimary end pointSafety end pointClinical events committeeMajor adverse eventsRate of restenosisDrug-Coated BalloonNoninferiority end pointSafety event rateAverage lesion lengthMajor amputationPopliteal diseaseRest painBailout stentingEfficacy ratePrimary patencyAdverse eventsSex-Specific Outcomes After Coronary Intravascular Lithotripsy: A Patient-Level Analysis of the Disrupt CAD Studies
Hussain Y, Kearney K, Abbott J, Kereiakes D, Di Mario C, Saito S, Cristea E, Riley R, Fajadet J, Shlofmitz R, Ali Z, Klein A, Price M, Hill J, Stone G, Lansky A. Sex-Specific Outcomes After Coronary Intravascular Lithotripsy: A Patient-Level Analysis of the Disrupt CAD Studies. Journal Of The Society For Cardiovascular Angiography & Interventions 2022, 1: 100011. PMID: 39130137, PMCID: PMC11307712, DOI: 10.1016/j.jscai.2021.100011.Peer-Reviewed Original ResearchPrimary efficacy end pointPrimary safety end pointMajor adverse cardiovascular eventsAdverse cardiovascular eventsEfficacy end pointSafety end pointIntravascular lithotripsyEnd pointCardiovascular eventsMyocardial infarctionHospital major adverse cardiovascular eventsMean reference vessel diameterCoronary intravascular lithotripsySevere coronary calcificationCoronary artery calcificationReference vessel diameterPercutaneous coronary interventionPrior myocardial infarctionSex-based outcomesSex-specific outcomesSide branch involvementPatient-level analysisSmall vessel sizeAngiographic complicationsLesion predilatation
2021
Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis
Lebwohl M, Stein Gold L, Strober B, Papp K, Armstrong A, Bagel J, Kircik L, Ehst B, Hong H, Soung J, Fromowitz J, Guenthner S, Piscitelli S, Rubenstein D, Brown P, Tallman A, Bissonnette R. Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. New England Journal Of Medicine 2021, 385: 2219-2229. PMID: 34879448, DOI: 10.1056/nejmoa2103629.Peer-Reviewed Original ResearchConceptsPrimary end pointPatient-reported outcomesTapinarof creamGlobal assessment scoreBody surface areaPlaque psoriasisWeek 12End pointPGA responseAdverse eventsPGA scoreMean changeSkin barrier protein filaggrinSecondary efficacy end pointsUpper respiratory tract infectionPhysician Global Assessment scoreNumeric rating scale scoreTotal body surface areaTotal scoreEfficacy end pointIdentical phase 3Local adverse eventsSymptom diary scoresProportion of patientsSecondary end pointsPopulation Pharmacokinetics and Exposure‐Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light‐Chain Amyloidosis
Luo M, Zhu P, Nnane I, Xiong Y, Merlini G, Comenzo R, Kastritis E, Wechalekar A, Weiss B, Tran N, Qin X, Vermeulen J, Sharma A, Sun Y, Zhou H. Population Pharmacokinetics and Exposure‐Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light‐Chain Amyloidosis. The Journal Of Clinical Pharmacology 2021, 62: 656-669. PMID: 34708423, DOI: 10.1002/jcph.1994.Peer-Reviewed Original ResearchConceptsLight chain amyloidosisSafety end pointSystemic exposureExposure-response analysesEnd pointsPopulation pharmacokineticsAmyloid light-chain amyloidosisNo dose adjustmentEfficacy end pointSystemic amyloid light-chain amyloidosisExposure-responseTreatment of light-chain amyloidosisImpact of potential covariatesLogistic regression analysisNonlinear mixed-effects modelingConcentration-time dataDexamethasone regimenDose adjustmentHematologic responseDaratumumabImmunogenicity dataPopPK analysisPopPK modelCharacteristics of Clinical Studies Used for US Food and Drug Administration Supplemental Indication Approvals of Drugs and Biologics, 2017 to 2019
Dhodapkar M, Zhang AD, Puthumana J, Downing NS, Shah ND, Ross JS. Characteristics of Clinical Studies Used for US Food and Drug Administration Supplemental Indication Approvals of Drugs and Biologics, 2017 to 2019. JAMA Network Open 2021, 4: e2113224. PMID: 34110392, PMCID: PMC8193429, DOI: 10.1001/jamanetworkopen.2021.13224.Peer-Reviewed Original ResearchConceptsPrimary efficacy end pointEfficacy end pointPivotal trialsIndication approvalsActive comparatorClinical outcomesSupplemental indicationsUS FoodEnd pointOriginal approvalTherapeutic areasPivotal efficacy trialsCross-sectional studyAdditional clinical dataDrug Administration approvalNew indication approvalsStrength of evidenceAdministration approvalMonths durationClinical dataClinical studiesEfficacy trialsMedian numberCancer indicationsMAIN OUTCOMEUpdated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0
Tolaney SM, Garrett-Mayer E, White J, Blinder VS, Foster JC, Amiri-Kordestani L, Hwang ES, Bliss JM, Rakovitch E, Perlmutter J, Spears PA, Frank E, Tung NM, Elias AD, Cameron D, Denduluri N, Best AF, DiLeo A, Baizer L, Butler LP, Schwartz E, Winer EP, Korde LA. Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0. Journal Of Clinical Oncology 2021, 39: 2720-2731. PMID: 34003702, PMCID: PMC10166345, DOI: 10.1200/jco.20.03613.Peer-Reviewed Original ResearchConceptsEfficacy end pointPrimary end pointBreast cancer clinical trialsPrimary cancerCancer clinical trialsEnd pointStandardized definitionsRecurrence rateClinical trialsInvasive disease-free survival eventsTherapy trialsBreast cancer-free survivalDisease-free survival eventsNon-breast cancer deathPrimary efficacy end pointClinical trial end pointsPhase III breast cancer trialsCancer-free survivalSecond primary cancerTrial end pointsAdditional end pointsBreast cancer trialsLow-risk populationPatient-reported outcomesSurvival end points
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