https://stroke.nottingham.ac.uk/maps-2/live/
https://forms.office.com/r/WTD38qxivXWe would love to have you on board!
| Title | The Metoclopramide for Avoiding Pneumonia after Stroke (MAPS-2) trial: a single-blind, randomised controlled trial of metoclopramide for the prevention of pneumonia in patients with dysphagia after an acute stroke. |
| Acronym | MAPS-2 |
| Short title | Metoclopramide for Avoiding Pneumonia after Stroke |
| Chief investigator | Christine Roffe |
| Objectives |
|
| Trial configuration | Two-arm parallel group single blind randomised controlled trial (Flow Chart) with an internal pilot |
| Setting | Emergency departments and stroke units of 90 or more NHS hospitals |
| Sample size estimate | The sample size has been calculated to detect a 20% relative reduction in mortality from 33% in the sham control group to 26.4% in the metoclopramide group at 6 months (equivalent to hazard ratio = 0.7654) with a power of 90%, using a two-sided log-rank test (Schoenfeld method) with a significance level of 5%, and 1:1 allocation. Assuming patients are followed-up to a maximum of 6 months, 588 deaths need to be observed. This requires 1980 participants (990 per arm) to be recruited. With 5% loss to follow-up, we aim to recruit approximately 2,100 participants. |
| Number of participants | 2100 |
| Eligibility criteria |
Inclusion criteria
Exclusion criteria
|
| Description of interventions |
Intervention: Metoclopramide solution for injection 10 mg/2 ml three times a day by slow IV injection or via nasogastric tube. For participants weighing less than 60 kg the dose will be reduced to 5 mg/1ml three times a day. Control: Normal saline solution for injection (sham control) 2 ml three times a day by slow intravenous injection or via nasogastric tube. Intervention/control treatment will be continued for 14 days or until discharge into the community, whichever is earlier. |
| Duration of study |
Study start date 1 Oct 2021 Duration for each participant: 6 months Study end date: 30 Apr 2025 |
| Randomisation and blinding | Participants will be individually randomised 1:1 via a web-based interface to metoclopramide or sham control by minimisation using NIHSS, age, mRS, time from stroke onset, and type of trial centre as factors. The trial will be single-blind (blinded assessment of primary outcome). |
| Outcome measures |
Primary outcome All-cause mortality (time-to-event) by 6 months Secondary outcomes at 14 days
Oculogyric crises Tardive dyskinesia Adverse events Discontinuations due to adverse events |
| Statistical methods |
The primary analysis will compare time to death between the metoclopramide and sham control, with analysis according to the allocated treatment regardless of treatment received (intention to treat). A Kaplan-Meier curve will compare the estimated survivor functions between arms. A Cox proportional hazards model will be used to calculate the hazard ratio and 95% confidence interval, censoring participants who have not died by 6 months or who are lost to follow-up. The model will be adjusted for the minimisation factors. As a sensitivity analysis, we will repeat the primary analysis by: (i) additionally adjusting for any variables with marked imbalance at baseline and for post-randomisation factors that are expected to affect outcome and (ii) treating the outcome as binary to obtain between-arm adjusted risk difference and risk ratio along with corresponding 95% confidence intervals. Should there be substantial missing data we will perform sensitivity analysis using imputation representing best and worst-case scenarios, to assess the effect of possible informative censoring, and/or use appropriate multiple imputation procedures for time-to-event data. Non-adherence is likely to be minimal at primary follow-up point as efforts will be made to maximise adherence with allocated treatment, but a sensitivity analysis based on complier average causal effect (CACE) will be performed to investigate the effects of adherence. Between-group comparison of secondary outcomes will be based on an appropriate regression model for the outcome (linear for continuous, logistic for binary, and proportional hazards for time-to event), adjusted for the same variables as the primary analysis. The level of significance used for all statistical tests will be 5%, two-tailed (p < 0.05). |
I am a stroke physician at the Royal Stoke University Hospital and Professor of Stroke Medicine at Keele University. I lead the National Institute for Health Research Hyperacute Stroke Research Centre Oversight Group. My key research interests are acute and hyperacute interventions for stroke, and the prevention of stroke complications, such as hypoxia and pneumonia.
Philip Bath is Stroke Association Professor of Stroke Medicine, as well as Chair and Head of the Division of Clinical Neuroscience at the University of Nottingham, and Co-chief Investigator of MAPS-2. He has extensive experience in a wide range of large national and international stroke studies and is leading international collaborations on improving the design and analysis of stroke studies.
Following a trauma-induced ischaemic stroke in 2005, Brin was forced to take early retirement from his teaching and Senior Management roles at The Sixth Form College Solihull in 2008. He had volunteered to participate in a stroke rehabilitation trial in 2006, and was quickly recruited to several other research trials in Birmingham, joining the WMSRN in 2009 and the National SRN Lay forum in 2010 where he sat on the Rehabilitation Clinical Studies group. Over the past 10 years, he has continued to support Stroke Research trials as an advisor, collaborator and co-applicant, or member of trial steering groups across the UK He is a member of the NIHR HSRC and a lay reviewer for NETSCC.
Hi I'm Di Havard, Senior Clinical Trial Manager for the University of Nottingham stroke trials. I have worked in stroke research since 2010. Amongst other roles I was the Lead Stroke Research Nurse for East Midlands before returning to Nottingham as the manager for TARDIS, TICH-2 and RIGHT-2 trials. I will now be working on MAPS-2, RECAST-3 and TICH-3.
I am a Senior Clinical Trial Manager within the Stroke Trials Unit, University of Nottingham, based at Queen's Medical Centre. I have 22 years' experience in research, as both a scientist and in research management. My background is somewhat varied, having worked in Pharma, Clinical Trials as well as many years in University research and teaching, in the fields of oncology, respiratory, diabetes and virology medical research, as well as a background in biochemistry, molecular and microbiology. I am working on the trials: MAPS-2 and PhEAST.
I am one of the trial managers responsible for overseeing the day-to-day operations of the MAPS-2 trial. My research background is in high blood pressure, particularly in pregnancy, and factors that influence blood pressure such as the reninangiotensin-system and platelet function. I have previously worked on studies funded by the British Heart Foundation at the University of Nottingham.
I graduated with a Master's degree in 2017 and joined the Oncology Research team at Nottingham University Hospitals NHS Trust shortly after. There I was responsible for facilitating the setup of new, exciting clinical trials for cancers of all types. I left the NHS in December 2020 and have been employed by the University of Nottingham since the beginning of 2021. I hope I can bring all the skills I have learnt to stroke clinical research.
I am a follow-up coordinator for the MAPS-2 trial. I have a background in Psychology and have 5 years' experience working for the NHS. My experience includes coordinating large multicentre studies as well as international studies. Much of my work consists of interventional studies using a combination of quantitative and qualitative research methods.
My name is Iris Isheanesu Mhlanga. I am the Medical Research Assistant who will be assisting and providing support in the statistical analysis and reporting sections of the MAPS-2 Trial.
I am a web application/database programmer for MAPS-2. My role is to develop and support software and systems for clinical trials, primarily relating to stroke research.
For any queries, please email us.