Dataset Information

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.

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.

SUBMITTER: Assayag EB

PROVIDER: S-EPMC9446318 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Assayag Einor Ben EB Molad Jeremy J Seyman Estelle E Rotschild Ofer O Zeltzer Ehud E Sadeh-Gonik Udi U Bregman Noa N Alpernas Aviva A Segal Yahel Y Bashat Dafna Ben DB Nathan Talya T Hawwari Muhamad M Tene Oren O Hallevi Hen H

European stroke journal 20220527 3

<h4>Background</h4>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 ce ...[more]

PMID: 36082248

Similar Datasets

Project description:IntroductionFollowing extubation from invasive mechanical ventilation, nearly one in seven critically ill adults requires reintubation. Reintubation is independently associated with increased mortality. Postextubation respiratory support (non-invasive ventilation or high-flow nasal cannula applied at the time of extubation) has been reported in small-to-moderate-sized trials to reduce reintubation rates among hypercapnic patients, high-risk patients without hypercapnia and low-risk patients without hypercapnia. It is unknown whether protocolised provision of postextubation respiratory support to every patient undergoing extubation would reduce the overall reintubation rate, compared with usual care.Methods and analysisThe Protocolized Post-Extubation Respiratory Support (PROPER) trial is a pragmatic, cluster cross-over trial being conducted between 1 October 2017 and 31 March 2019 in the medical intensive care unit of Vanderbilt University Medical Center. PROPER compares usual care versus protocolized post-extubation respiratory support (a respiratory therapist-driven protocol that advises the provision of non-invasive ventilation or high-flow nasal cannula based on patient characteristics). For the duration of the trial, the unit is divided into two clusters. One cluster receives protocolised support and the other receives usual care. Each cluster crosses over between treatment group assignments every 3 months. All adults undergoing extubation from invasive mechanical ventilation are enrolled except those who received less than 12 hours of mechanical ventilation, have 'Do Not Intubate' orders, or have been previously reintubated during the hospitalisation. The anticipated enrolment is approximately 630 patients. The primary outcome is reintubation within 96 hours of extubation.Ethics and disseminationThe trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.Trial registration numberNCT03288311.

Project description:BackgroundTransforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However, their safety, effectiveness, and cost-effectiveness are still a matter of debate. This a priori statistical analysis plan describes the methodology of the analysis for the STAR trial that assesses the (cost-)effectiveness of TESI during the acute stage of sciatica (< 8 weeks).MethodsThe STAR trial is a multicentre, randomized controlled, prospective trial (RCT) investigating the (cost-)effectiveness of TESI by making a three-group comparison among patients with acute sciatica due to a herniated lumbar disc (< 8 weeks): (1) TESI combined with levobupivacaine added to oral pain medication (intervention group 1) versus oral pain medication alone (control group), (2) intervention group 1 versus transforaminal epidural injection with levobupivacaine and saline solution added to oral pain medication (intervention group 2), and (3) intervention group 2 versus control group. Co-primary outcomes were physical functioning (Roland Morris Disability Questionnaire), pain intensity (10-point numerical rating scale), and global perceived recovery (7-point Likert scale, dichotomized into 'recovered' and 'not recovered'). For all three comparisons, we defined the following minimal clinically relevant between-group differences: two points for pain intensity (range 0-10), four points for physical functioning (range 0-24) and a 20% difference in recovery rate. Secondary outcomes are health-related quality of life (EQ-5D-5L) and patient satisfaction (7-point Likert scale) and surgery rate. We also collected resource use data to perform an economic evaluation. Analyses will be conducted by intention-to-treat with p < 0.05 (two-tailed) for all three comparisons. Effects will be estimated using mixed models by maximum likelihood. For each comparison, mean differences, or difference in proportions, between groups will be tested per time point and an overall mean difference, or difference in proportions, between groups during the complete duration of follow-up (6 months) will be estimated. In the economic evaluation, Multivariate Imputation by Chained Equations will be used to handle missing data. Cost and effect differences will be estimated using seemingly unrelated regression, and uncertainty will be estimated using bootstrapping techniques.DiscussionThis statistical analysis plan provides detailed information on the intended analysis of the STAR trial, which aims to deliver evidence about the (cost-)effectiveness of TESI during the acute phase of sciatica (< 8 weeks).Trial registrationDutch National trial register NTR4457 (6 March 2014).

Dataset Information

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.

Background

Design

Outcomes

Conclusions

Schedule

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets