Selection design phase II trial of high dosages of tamoxifen and creatine in amyotrophic lateral sclerosis
Babu S, Macklin EA, Jackson KE, Simpson E, Mahoney K, Yu H, Walker J, Simmons Z, David WS, Barkhaus PE, Simionescu L, Dimachkie MM, Pestronk A, Salameh JS, Weiss MD, Brooks BR, Schoenfeld D, Shefner J, Aggarwal S, Cudkowicz ME, Atassi N
Amyotrophic lateral sclerosis & frontotemporal degeneration · 13 citas
Etiquetas de revisión
Financiación no declaradaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2019-10-14 · Amyotroph Lateral Scler Frontotemporal Degener · vol. 21 · número 1-2 · págs. 15–23
- Editorial
- Taylor & Francis
- Citado
- 19 citas · más que el 82% de estudios similares · 1.6× el promedio de su campo
- Referencias
- 36 trabajos
- Acceso
- De pago
- Áreas de investigación
- Amyotrophic Lateral Sclerosis Research · Statistical Methods in Clinical Trials · Alzheimer's disease research and treatments
- Palabras clave
- amyotrophic lateral sclerosis, tamoxifen, creatine, slow vital capacity, drug-related adverse events, trial efficiency, adaptive platform trial
- MeSH
- humans, amyotrophic lateral sclerosis, creatine, tamoxifen, vital capacity, double-blind method, adult, aged, middle aged, female, male, muscle strength
21 autores
- Suma Babu🇺🇸 · autor de correspondenciaMassachusetts General Hospital
- Eric A. Macklin🇺🇸Harvard University; Massachusetts General Hospital
- Katherine E. Jackson🇺🇸Maryland Department of Health
- Elizabeth Simpson🇺🇸Massachusetts General Hospital
- Katy Mahoney🇺🇸Massachusetts General Hospital
- Hong Yu🇺🇸Massachusetts General Hospital
- Jason Walker🇺🇸Massachusetts General Hospital
- Zachary Simmons🇺🇸Pennsylvania State University; Penn State Milton S. Hershey Medical Center
- William S. David🇺🇸Massachusetts General Hospital
- Paul E. Barkhaus🇺🇸Medical College of Wisconsin
- Laura E. Simionescu🇺🇸SUNY Upstate Medical University
- Mazen M. Dimachkie🇺🇸University of Kansas Medical Center
- Alan Pestronk🇺🇸Washington University in St. Louis
- Johnny S. Salameh🇱🇧American University of Beirut Medical Center
- Michael D. Weiss🇺🇸University of Washington Medical Center
- Benjamin Rix Brooks🇺🇸Carolinas Medical Center
- David Schoenfeld🇺🇸Harvard University; Massachusetts General Hospital
- Jeremy M. Shefner🇺🇸Barrow Neurological Institute; University of Arizona College of Medicine- Phoenix
- Swati Aggarwal🇺🇸Massachusetts General Hospital
- Merit Cudkowicz🇺🇸Massachusetts General Hospital
- Nazem Atassi🇺🇸Massachusetts General Hospital
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective: To conduct a phase-II trial using a ranking and selection paradigm where multiple treatments are compared with limited sample size and the best is chosen for a subsequent efficacy trial versus placebo. This strategy can find an effective treatment faster than traditional strategy of conducting larger trials against placebo. Methods: Sixty amyotrophic lateral sclerosis (ALS) participants were randomized 1:1:1 to creatine 30 g/day (CRE), tamoxifen 40 mg/day (T40), or tamoxifen 80 mg/day (T80), with matching placebo. The primary outcome was 38-week change in ALS Functional Rating Scale-Revised (ALSFRS-R), analyzed in a repeated-measures ANOVA. Secondary outcomes included slow vital capacity (SVC), quantitative muscle strength, early drug discontinuation (EDD), adverse events (AEs), and survival. Results: CRE participants experienced higher rates of drug-related AEs (82% vs. 43% T40, 47% T80) and EDD (50% vs. 24% T40, 29% T80). T80 participants experienced slower adjusted mean decline in ALSFRS-R in points/month (-0.80 vs. -0.84 T40, -0.85 CRE) and quantitative muscle strength but not in SVC and higher rates of mortality. Conclusion: Efficacy of T80 ranked numerically superior to CRE and T40 with respect to ALSFRS-R decline. Following the selection paradigm, T80 would be chosen to test against placebo. The approach was not designed to distinguish among treatments that are nearly equally effective or ineffective. If treatments are equivalent, then under the paradigm, it does not matter which treatment is selected. Newer approaches for increasing trial efficiency, including an adaptive platform trial design, may mitigate limitations of the selection design.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.