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Lookup NU author(s): Dr Duddy Duddy
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. INTRODUCTION: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS. METHODS AND ANALYSIS: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0-6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur. ETHICS AND DISSEMINATION: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBERS: NCT03387670; ISRCTN82598726.
Author(s): Blackstone J, Williams T, Nicholas JM, Bordea E, De Angelis F, Bianchi A, Calvi A, Doshi A, John N, Apap Mangion S, Wade C, Merry R, Barton G, Lyle D, Jarman E, Mahad D, Shehu A, Arun T, McDonnell G, Geraldes R, Craner M, Hillier C, Ganesalingam J, Fisniku L, Hobart J, Spilker C, Robertson N, Kalra S, Pluchino S, Harikrishnan S, Mattoscio M, Harrower T, Young C, Lee M, Chhetri S, Ahmed F, Rog D, Silber E, Gallagher P, Duddy M, Straukiene A, Nicholas R, Rice C, Nixon SJ, Beveridge J, Hawton A, Tebbs S, Braisher M, Giovannoni G, Ciccarelli O, Greenwood J, Thompson AJ, Hunter R, Pavitt S, Pearson O, Evangelou N, Sharrack B, Galea I, Chandran S, Ford HL, Frost C, Chataway J
Publication type: Article
Publication status: Published
Journal: BMJ Open
Year: 2024
Volume: 14
Issue: 9
Online publication date: 16/09/2024
Acceptance date: 16/08/2024
Date deposited: 30/09/2024
ISSN (print): 2044-6055
ISSN (electronic): 2044-6055
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/bmjopen-2024-086414
DOI: 10.1136/bmjopen-2024-086414
PubMed id: 39284697
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