Rationale and Design of an Adaptive Phase 2b/3 Clinical Trial of Selepressin for Adults in Septic Shock Selepressin Evaluation Programme for Sepsis-induced Shock-Adaptive Clinical Trial
| Autor: | Derek C. Angus, Anders Perner, Steven M. Opal, Jan E. Carlsen, James A. Russell, Anne Louise Kjølbye, Egbert van der Meulen, Pierre-François Laterre, Bruno François, Roger J. Lewis, Karsten Jacobsen, Todd Graves, Donald M. Yealy, Scott M. Berry, Nis A. Windeløv, Peter Pickkers, Allan Blemings |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Receptors Vasopressin medicine.medical_specialty Randomization Vasopressins lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] 030204 cardiovascular system & hematology Risk Assessment Sepsis 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center 0302 clinical medicine Clinical Protocols Humans Vasoconstrictor Agents Medicine 030212 general & internal medicine Dosing Infusions Intravenous Intensive care medicine Adaptive clinical trial Dose-Response Relationship Drug business.industry Septic shock medicine.disease Shock Septic Clinical trial Treatment Outcome Research Design Sample size determination Shock (circulatory) Female Drug Monitoring Hypotension medicine.symptom business |
| Zdroj: | Annals of the American Thoracic Society, 15, 250-257 Annals of the American Thoracic Society, 15, 2, pp. 250-257 |
| ISSN: | 2325-6621 |
| Popis: | Septic shock carries substantial morbidity and mortality. The failure of many promising therapies during late-phase clinical trials prompted calls for alternative trial designs. We describe an innovative trial evaluating selepressin, a novel selective vasopressin V1a receptor agonist, for adults with septic shock. SEPSIS-ACT (Selepressin Evaluation Programme for Sepsis-induced Shock—Adaptive Clinical Trial) is a blinded, randomized, placebo-controlled, two-part, adaptive phase 2b/3 trial, evaluating up to four selepressin dosing strategies. The primary outcome is pressor- and ventilator-free days, with a value of zero assigned for death within 30 days. We calculate Bayesian probabilities of final trial success to guide interim decision-making. Part 1 (dose-finding) has an adaptive sample size based on response-adaptive randomization and prespecified rules to determine stopping for futility or selection of the best dosing regimen for Part 2. Part 2 (confirmation) randomizes a minimum of 1,000 patients equa... |
| Databáze: | OpenAIRE |
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