MAPS-2 trial
Metoclopramide for Avoiding Pneumonia after Stroke 2

ISRCTN: 40512746
EudraCT number: 2021-003853-40
CTA reference: 2021-003853-40
IRAS Project ID: 290474
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Welcome!

This site has been created as a resource for MAPS-2 researchers, co-ordinating centres, patients, relatives and carers alike.  We hope you enjoy browsing our site and finding all the information you need!

The MAPS study is back!

As with the original MAPS clinical trial published back in 2014, the MAPS-2 trial is further investigating whether the anti-sickness drug, metoclopramide, can help reduce mortality in patients with dysphagia after stroke.  The MAPS-2 trial is also looking at whether the use of metoclopramide can help prevent pneumonia and improve long-term outcomes for these patients.  If you would like to learn more about the trial, please refer to the MAPS-2 protocol synopsis.

MAPS-2 trial is now recruiting!

To start recruitment and submit trial data, please use the following link to access REDCap.
https://stroke.nottingham.ac.uk/maps-2/live/

Expressions of interest

If you are a researcher and are interested in your co-ordinating centre participating in the MAPS-2 study, please use the below link to complete the expression of interest form.
https://forms.office.com/r/WTD38qxivX
We would love to have you on board!

Sites that have filled in an expression of interest form, as of 14 Oct 2021.

  1. Aberdeen, Aberdeen Royal Infirmary
  2. Aberystwyth, Bronglais General Hospital
  3. Airdrie, University Hospital Monklands
  4. Basildon, Mid & South Essex Hospital - Basildon
  5. Bath, Royal United Hospital Bath
  6. Bournemouth, University Hospital Dorset - The Royal Bournemouth Hospital
  7. Bradford, Bradford Royal Infirmary
  8. Bristol, Southmead Hospital
  9. Cambridge, Cambridge University Hospital, Addenbrooke's Hospital
  10. Cardiff, University Hospital of Wales
  11. Carlisle, Cumberland Infirmary Carlisle
  12. Carmarthen, Glangwilli General Hospital
  13. Chester, Countess of Chester NHS Foundation Trust
  14. Colchester, Colchester General Hospital
  15. Coventry, University Hospitals Coventry and Warwickshire
  16. Crewe, Leighton Hospital - Mid Cheshire Hospital Trust
  17. Derby, Royal Derby Hospital
  18. Derry (Northern Ireland), Altnagelvin hospital (western trust)
  19. Dundee, Ninewells Hospital and Medical School
  20. Durham, University Hospital of North Durham
  21. Enniskillen, South West Acute Hospital
  22. Exeter, Royal Devon & Exeter Hospital, Exeter, UK
  23. Farnborough/Surrey, Frimley Health NHS Foundation Trust
  24. Gateshead, Queen Elizabeth Hosptial Gateshead
  25. Glasgow, Glasgow Royal Infirmary
  26. Guildford Surrey, The Royal Surrey NHS Foundation Trust
  27. High Wycombe, Wycombe General hospital
  28. Larbert, Fourth Valley Royal Hospital
  29. Leeds, Leeds Teaching Hospitals NHS Trust
  30. Leicester, Leicester Royal Infirmary
  31. Liverpool, Royal Liverpool University Hospital
  32. London, King's College Hospital NHS Foundation Trust (Princess Royal University Hospital)
  33. London, King's College Hospital NHS Foundation Trust
  34. London, Newham University Hospital (repatriation)
  35. London, Northwick Park Hospital (London North West University Healthcare Trust)
  36. London, Royal London Hospital
  37. London, St George's University Hospitals NHS Foundation Trust, London
  38. London, Whipps Cross (repatriation)
  39. Luton, Luton and Dunstable University Hospital NHS Trust
  40. Manchester, Salford Royal
  41. Middlesborough, James Cook University Hospital
  42. Milton Keynes, Milton Keynes University Hospital
  43. Newcastle Upon Tyne, Royal Victoria Infirmary - Newcastle Upon Tyne
  44. North Tees and Hartlepool, North Tees Hospital
  45. Northampton, Northampton General Hospital NHS Trust
  46. Norwich, Norfolk and Norwich University Hospital
  47. Nottingham, Nottingham University Hospitals NHS Trust
  48. Peterborough, North West Anglia - Peterborough City Hospital and Hinchingbrooke Hospital
  49. Poole, University Hospital Dorset NHS Trust
  50. Prescot, St Helens & Knowsley Teaching Hospitals NHS Trust
  51. Preston/Chorley, Lancashire Teaching Hospitals NHS Foundation Trust
  52. Sheffield, Sheffield Teaching Hospitals Royal Hallamshire Hospital
  53. South Tyneside & Sunderland, Sunderland Royal Hospital
  54. Southampton, University Hospital Southampton
  55. Stockport , Stepping Hill Hospital
  56. Stoke, Royal Stoke University Hospital
  57. Stoke-on-Trent, University Hospitals of North Midlands NHS Trust
  58. Surrey, East Surrey Hospital
  59. Swansea, Morriston Hospital
  60. Torbay, Torbay and South Devon NHS Foundation Trust
  61. Truro, Royal Cornwall
  62. West Suffolk, West Suffolk NHS Foundation Trust
  63. Whitehaven, West Cumberland Hospital Whitehaven
  64. Worthing/Chichester, University Hospitals Sussex NHS Foundation Trust
  65. Yeovil, Yeovil District Hospital

Synopsis

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
  1. To assess whether metoclopramide reduces mortality in patients with dysphagia after stroke
  2. To assess whether metoclopramide reduces pneumonia and improves neurological recovery at 14 days
  3. To assess whether metoclopramide improves long-term outcomes (6 months)
  4. To assess cost-effectiveness and cost-utility
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
  1. Adults (at least 18 years old) with a clinical diagnosis of acute stroke
  2. Within 24 hours of symptom onset
  3. One of the two below criteria:
    3a. Moderate to severe neurological impairment (NIHSS Score ≥ 10), or
    3b. Dysphagia and NIHSS ≥ 6, unable to take normal unmodified oral diet or fluids because:
    (a) Too drowsy to be assessed formally or
    (b) Failed bedside assessment of swallowing

Exclusion criteria
  1. Definite or probable pneumonia at screening
  2. Contraindications to metoclopramide
  3. Clinical indication for regular antiemetic treatment
  4. Known cirrhosis of the liver
  5. Known severe renal dysfunction (eGFR < 30 ml/min)
  6. Pregnant or breast feeding
  7. Moribund (expected to die within the next 48 hours)
  8. Co-morbid conditions with life expectancy <3 months
  9. Inability to gain consent (patient or legal representative) or consent declined
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
  1. Pneumonia (clinician diagnosis)
  2. Pneumonia (criteria-based)
  3. No of days of antibiotic treatment
  4. Ability to swallow (DSRS)
  5. Neurological recovery (NIHSS Stroke Scale)
  6. Quality of life (EQ-5D 5L™
Secondary outcomes at 6 months
  1. Functional status (modified Rankin Scale)
  2. Ability to swallow (DSRS)
  3. Frailty (CFS)
  4. Home time (no. of days spent at home rather than in hospital or care home)
  5. Quality of life (EQ-5D 5L™)
Health economic outcomes
  1. Cost per death avoided over 6 months
  2. Cost per QALY gained over 6 months
  3. Cost per QALY gained over patient lifetime
Safety outcomes to the end of treatment (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).

Trial staff

Last updated on 7 Jul 2022

Professor Christine Roffe
Chief Investigator
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.

Professor Christine Roffe

Professor Philip Bath
Co-chief Investigator
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.

Professor Philip Bath

Brinton Helliwell
PPI Group
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.

Brinton Helliwell

Diane Havard
Senior Clinical Trials Manager
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.

Diane Havard

Dr Tiffany Hamilton
Senior Clinical Trials Manager
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.

Dr Tiffany Hamilton

Dr Lesia Kurlak
Clinical Trials Manager
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.

Dr Lesia Kurlak

Cameron Skinner
Clinical Trials Manager
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.

Cameron Skinner

Jared Palmer
Follow-Up Coordinator
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.

Jared Palmer

Iris Mhlanga
Medical Research Assistant
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.

Iris Mhlanga

Corinne Latulipe
Web application/database programmer
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.

Newsflashes

Contact us

Room S/D2105
Stroke Trials Unit
School of Medicine
University of Nottingham
Queen's Medical Centre
Derby Road
Nottingham NG7 2UH
United Kingdom

Tel: 0115 823 1665

For any queries, please email us.

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