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. 2022 Sep;7(3):314-322.
doi: 10.1177/23969873221098857. Epub 2022 May 27.

Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment

Einor Ben Assayag  1   2 , Jeremy Molad  1 , Estelle Seyman  1 , Ofer Rotschild  1 , Ehud Zeltzer  1 , Udi Sadeh-Gonik  1 , Noa Bregman  1   2 , Aviva Alpernas  1 , Yahel Segal  1 , Dafna Ben Bashat  1   2 , Talya Nathan  1 , Muhamad Hawwari  1 , Oren Tene  1   2 , Hen Hallevi  1   2
Affiliations

Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment

Einor Ben Assayag et al. Eur Stroke J. 2022 Sep.

Abstract

Background: Current evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI.

Design: MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging.

Outcomes: Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups.

Conclusions: The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease.

Schedule: First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.

Keywords: Maraviroc; Post-stroke dementia; randomized controlled trial; white matter hyperintensities.

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Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flow-chart of study procedures.
See this image and copyright information in PMC

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