Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial

Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in...

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Detalles Bibliográficos
Autores: Chataway, Simon Jeremy, Angelis, Floriana de, Connick, Peter, Parker, Richard, Plantone, Domenico, Doshi, Anisha, John, Nevin Alex, Stutters, Jonathan, MacManus, David, Prados Carrasco, Ferran, Barkhof, Frederik, Ourselin, Sebastien, Braisher, Marie, Ross, Moira, Cranswick, Gina, Pavitt, Sue H., Giovannoni, Gavin, Gandini Wheeler-Kingshott, Claudia A.M., Hawkins, Clive, Sharrack, Basil, Bastow, Roger, Weir, Christopher J., Stallard, Nigel, Chandran, Siddharthan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Oberta de Catalunya (UOC)
Repositorio:O2, repositorio institucional de la UOC
OAI Identifier:oai:openaccess.uoc.edu:10609/122146
Acceso en línea:https://hdl.handle.net/10609/122146
Access Level:acceso abierto
Palabra clave:secondary progressive multiple sclerosis
neurodegeneration
neuroprotective drugs
neurodegeneració
fàrmacs neuroprotectors
esclerosi múltiple secundària progressiva
neurodegeneración
fármacos neuroprotectores
esclerosis múltiple secundaria progresiva
Multiple sclerosis
Esclerosi múltiple
Esclerosis múltiple
Descripción
Sumario:Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource. Methods: We did a phase 2b, multiarm, parallel group, double-blind, randomised placebo-controlled trial at 13 clinical neuroscience centres in the UK. We recruited patients (aged 25-65 years) with secondary progressive multiple sclerosis who were not on disease-modifying treatment and who had an Expanded Disability Status Scale (EDSS) score of 4·0-6·5. Participants were randomly assigned (1:1:1:1) at baseline, by a research nurse using a centralised web-based service, to receive twice-daily oral treatment of either amiloride 5 mg, fluoxetine 20 mg, riluzole 50 mg, or placebo for 96 weeks. The randomisation procedure included minimisation based on sex, age, EDSS score at randomisation, and trial site. Capsules were identical in appearance to achieve masking. Patients, investigators, and MRI readers were unaware of treatment allocation. The primary outcome measure was volumetric MRI percentage brain volume change (PBVC) from baseline to 96 weeks, analysed using multiple regression, adjusting for baseline normalised brain volume and minimisation criteria. The primary analysis was a complete-case analysis based on the intention-to-treat population (all patients with data at week 96). This trial is registered with ClinicalTrials.gov, NCT01910259.

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