Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART).:a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis
Autor: | Connick, P, De Angelis, F, Parker, Ra, Plantone, D, Doshi, A, John, N, Stutters, J, Macmanus, D, Prados Carrasco, F, Barkhof, F, Ourselin, S, Braisher, M, Ross, M, Cranswick, G, Pavitt, Sh, Giovannoni, G, Gandini Wheeler-Kingshott CA, Hawkins, C, Sharrack, B, Bastow, R, Weir, Cj, Stallard, N, Chandran, S, Chataway, J, UK Multiple Sclerosis Society Clinical Trials, Network. |
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Přispěvatelé: | Radiology and nuclear medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Serotonin reuptake inhibitor Placebo Amiloride 03 medical and health sciences 0302 clinical medicine Atrophy Double-Blind Method Fluoxetine Internal medicine Statistical significance Protocol medicine Humans Riluzole drug repurposing business.industry Multiple sclerosis clinical trial General Medicine Middle Aged Multiple Sclerosis Chronic Progressive RC346 mechanistic evaluation medicine.disease 3. Good health Clinical trial progressive multiple sclerosis Neuroprotective Agents Treatment Outcome 030104 developmental biology Neurology neuroprotection Female business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Connick, P, De Angelis, F, Parker, R, Plantone, D, Doshi, A, John, N, Stutters, J, MacManus, D, Prados Carrasco, F, Barkhof, F, Ourselin, S, Braisher, M, Ross, M & Cranswick, G & Weir, C 2018, ' Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART). a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis ', BMJ Open . https://doi.org/10.1136/bmjopen-2018-021944 Connick, P, De Angelis, F, Parker, R A, Plantone, D, Doshi, A, John, N, Stutters, J, Macmanus, D, Prados Carrasco, F, Barkhof, F, Ourselin, S, Braisher, M, Ross, M, Cranswick, G, Pavitt, S H, Giovannoni, G, Gandini Wheeler-Kingshott, C A, Hawkins, C, Sharrack, B, Bastow, R, Weir, C J, Stallard, N, Chandran, S & Chataway, J 2018, ' Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) : A multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis ', BMJ Open, vol. 8, no. 8, e021944 . https://doi.org/10.1136/bmjopen-2018-021944 BMJ Open, 8(8):e021944. BMJ Publishing Group BMJ Open |
ISSN: | 2044-6055 |
DOI: | 10.1136/bmjopen-2018-021944 |
Popis: | IntroductionThe major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist).Methods and analysisPatients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland.Ethics and disseminationMS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration numbersNCT01910259; 2012-005394-31;ISRCTN28440672. |
Databáze: | OpenAIRE |
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