Metoclopramide for avoiding pneumonia after stroke
| ISRCTN | ISRCTN40512746 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN40512746 |
| EudraCT/CTIS number | 2021-003853-40 |
| IRAS number | 290474 |
| Secondary identifying numbers | HTA - NIHR130689, IRAS 290474 |
- Submission date
- 25/05/2021
- Registration date
- 17/06/2021
- Last edited
- 18/10/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English Summary
Background and study aims
Stroke is the fourth most common cause of death in the UK. Despite great progress over the last 20 years, the only treatments shown to reduce the death rate are admission to a specialist stroke unit, prevention of blood clots by intermittent pneumatic leg compression, and surgery for brain swelling. Pneumonia is the most common cause of death after stroke and, even if not fatal, weakens the patient and delays recovery. Patients with a stroke often lose the ability to swallow safely. This can lead to food and drink spilling into the lungs. Stroke patients with swallowing problems are therefore at high risk of pneumonia.
When stroke patients are turned in bed, moved, or even when just resting in bed, they often vomit and inhale the contents of the mouth and/or stomach into the lungs. This is the most common cause of pneumonia after stroke. In a small pilot study conducted in a single hospital the researchers were able to show that metoclopramide, an anti-sickness drug, prevents pneumonia in patients with severe stroke when given regularly in the first 2 weeks. The aim of this study is to confirm this finding in a wider range of hospitals and to establish whether this can also reduce the number of patients who die from stroke.
This study will test whether metoclopramide, given early after stroke onset and continued for 2 weeks, is better than sham control (dummy treatment) for preventing pneumonia and death after stroke.
Who can participate?
Adult patients admitted to hospital with moderate to severe acute stroke and dysphagia within 9 hours of symptom onset
What does the study involve?
The duration of each participant's involvement in the study will be 6 months. Participants are allocated randomly to be treated with metoclopramide hydrochloride or a normal saline solution through a vein or tube into the nose (nasogastric tube) three times a day for 14 days or until discharge into the community, if this is before 14 days. For each patient, a daily log of whether they have signs or symptoms of pneumonia and if they have any side effects will be recorded for 2 weeks. A neurological assessment, to see how the patient is recovering from their stroke, will be made on day 14. After 6 months, the patient or their carer will be telephoned by a member of the study team to assess their level of disability (if any), their quality of life, whether they still have problems swallowing, if they are still in hospital or, if not, where they are living. A health economic analysis will be done to look at potential cost savings as a result of shorter hospital stays and fewer re-admissions.
What are the possible benefits and risks of participating?
There are no expected benefits. If the treatment is effective, it might prevent pneumonia and reduce the risk of death, but this is not guaranteed.
Where is the study run from?
University of Nottingham (UK)
When is the study starting and how long is it expected to run for?
February 2021 to May 2027
Who is funding the study?
National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA)(UK).
Who is the main contact?
Christine Roffe
christine.roffe@uhnm.nhs.uk
Contact information
Scientific
31 Moody Street
Congleton
CW12 4AN
United Kingdom
 ORCID ID |
0000-0002-5259-6649 |
|---|---|
| Phone | +44 (0)7740 372852 |
| christine.roffe@uhnm.nhs.uk |
Public
Clinical Neuroscience
University of Nottingham
Queen’s Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
| Phone | +44 (0)7740 372852 |
|---|---|
| ms-maps-2@exmail.nottingham.ac.uk |
Study information
| Study design | Multicentre phase III participant-blinded parallel two-arm randomized sham-controlled trial with an internal pilot |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | The Metoclopramide for Avoiding Pneumonia after Stroke (MAPS-2) trial: a single-blind, randomized controlled trial of metoclopramide for the prevention of pneumonia in patients with dysphagia after an acute stroke |
| Study acronym | MAPS-2 |
| Study hypothesis | Pneumonia is a major cause of death after stroke. It is most commonly caused by aspiration of vomited or regurgitated gastric contents. Prevention of regurgitation and vomiting by regular administration of an antiemetic (metoclopramide) could improve outcomes by prevention of pneumonia. the hypothesis to be tested in this study is that metoclopramide, started early after symptom onset and continued for 14 days will reduce mortality and prevent pneumonia after stroke. |
| Ethics approval(s) |
Approved 17/11/2021, East Midlands – Nottingham 2 Research Ethics Committee (Equinox House, City Link, Nottingham, NG2 4LA, United Kingdom; +44 207 10148051; nottingham2.rec@hra.nhs.uk), ref: 21/EM/0246 |
| Condition | Prevention of pneumonia caused by dysphagia after an acute stroke |
| Intervention | Participants will be individually randomized 1:1 via a web-based interface to metoclopramide or sham control by minimization using NIH Stroke Scale/Score (NIHSS), age, modified Rankin score (mRS), time from stroke onset, and type of trial centre as factors. The trial will be single-blind with blinded assessment of primary outcome. Intervention: Metoclopramide hydrochloride (5 mg per 1 ml solution for injection) 2 ml (10 mg) to be given iv or via nasogastric tube three times a day for 14 days or until discharge into the community, if this is before 14 days. Reduce dose to 1 ml (5 mg) if bodyweight <60 kg. Control: Sodium chloride (0.9% solution for injection) 2 ml to be given iv or via nasogastric tube three times a day for 14 days or until discharge into the community, if this is before 14 days. Reduce dose to 1 ml if bodyweight <60 kg. For each patient, a daily log of whether they have signs or symptoms of pneumonia and if they have any side effects will be recorded for 2 weeks. A neurological assessment, to see how the patient is recovering from their stroke, will be made on day 14. After 6 months, the patient or their carer will be telephoned by a member of the study team to assess: their level of disability (if any); their quality of life; whether they still have problems swallowing; if they are still in hospital or, if not, where they are living. A health economic analysis will be done to look at potential cost savings as a result of shorter hospital stays and fewer re-admissions. Health economic outcomes are: 1. Cost per death avoided over 6 months 2. Cost per quality-adjusted life-year (QALY) gained over 6 months 3. Cost per QALY gained over patient lifetime |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Metoclopramide |
| Primary outcome measure | All-cause mortality by 6 months (time-to-event), ascertained by contacting the general practitioner in the first instance. Missing data will be completed with the team who recruited the patient and via linkage with Hospital Episode Statistics and The Office of National Statistics. |
| Secondary outcome measures | 1. Development of pneumonia, diagnosed by the clinical care team and retrieved from medical notes at 14 days 2. Development of pneumonia specifically attributed to the stroke event (diagnosis based on standard criteria determined by the Stroke Consensus group published in 2015) retrieved from daily clinical log at 14 days 3. Antibiotic treatment, measured as the number of days on treatment, retrieved from medical notes and drug charts at 14 days 4. Difficulty in swallowing measured using the standard Dysphagia Severity Rating Scale Score (DSRS) at 14 days and 6 months 5. Severity of stroke assessed by the NIH Stroke Score at baseline and 14 days 6. Quality of life assessed by the EuroQol EQ-5D questionnaire at 14 days and 6 months 7. Degree of disability evaluated by an ordinal shift in the modified Rankin score (mRS) at 6 months 8. Vulnerability to poor health outcomes assessed by Clinical Frailty Scale index at 6 months 9. Home time, defined as the number of days spent at home rather than hospitalised, at 6 months |
| Overall study start date | 01/02/2021 |
| Overall study end date | 31/05/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 2100 |
| Participant inclusion criteria | Current inclusion criteria as of 04/04/2024: 1. Adults (18 years and over) with a clinical diagnosis of acute stroke (WHO definition excluding duration) 2. Within 24 hours of symptom onset (in wake-up stroke the onset is defined as the time the patient awoke or was found unless this is more than 12 h from last known well) 3. One of the two below criteria: 3a. Moderate to severe neurological impairment (NIH Stroke Scale/Score (NIHSS) ≥10) OR 3b. Dysphagia and NIHSS ≥6, unable to take normal unmodified oral diet or fluids because: i) Too drowsy to be assessed formally or ii) Failed bedside assessment of swallowing _____ Previous inclusion criteria as of 14/03/2023: 1. Adults (18 years and over) with a clinical diagnosis of acute stroke (WHO definition excluding duration) 2. Within 24 hours of symptom onset (in wake-up stroke the onset is defined as the time the patient awoke or was found unless this is more than 12 h from last known well) 3. Moderate to severe neurological impairment (NIH Stroke Scale/Score (NIHSS) ≥10) 4. Unable to take normal unmodified oral diet or fluids because: 4.1. Too drowsy to be assessed formally or 4.2. Failed bedside assessment of swallowing _____ Previous inclusion criteria: 1. Adults (18 years and over) with a clinical diagnosis of acute stroke (WHO definition excluding duration) 2. Within 9 hours of symptom onset (in wake-up stroke the onset is defined as the time the patient awoke or was found unless this is more than 12 h from last known well) 3. Moderate to severe neurological impairment (NIH Stroke Scale/Score (NIHSS) ≥10) 4. Unable to take normal unmodified oral diet or fluids because: 4.1. Too drowsy to be assessed formally or 4.2. Failed bedside assessment of swallowing |
| Participant exclusion criteria | 1. Definite or probable pneumonia (abnormal chest X-ray suggestive of pneumonia or focal chest signs with fever ≥38°C, or receiving antibiotic treatment at time of presentation) 2. Contraindications to metoclopramide (hypersensitivity to metoclopramide, epilepsy, gastrointestinal obstruction, perforation, or haemorrhage, gastrointestinal surgery within the last week, Parkinson’s disease, treatment with levodopa or dopaminergic agonists, phaeochromocytoma or neuroleptic malignant syndrome or tardive dyskinesia or methaemoglobinaemia or NADH cytochrome –b5 deficiency) 3. Clinical indication for regular antiemetic treatment 4. Known cirrhosis of the liver 5. Known severe renal dysfunction (eGFR <30 ml/hour) 6. Pregnant or breastfeeding 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 |
| Recruitment start date | 28/02/2022 |
| Recruitment end date | 31/10/2026 |
Locations
Countries of recruitment
- England
- Northern Ireland
- United Kingdom
- Wales
Study participating centres
Whitechapel
London
E1 1FR
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Derby Road
Lenton
Nottingham
NG7 2UH
United Kingdom
Hardwick Lane
Bury St Edmunds
IP33 2OZ
United Kingdom
New Victoria Wing
Newcastle Upon Tyne
NE1 4LP
United Kingdom
Middlewich Road
Crewe
CW1 4QJ
United Kingdom
Middlesbrough
T34 3BW
United Kingdom
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Enniskillen
BT74 6DN
United Kingdom
Denmark Hill
London
SE5 9RS
United Kingdom
Cliftonville
Northampton
NN1 5BD
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
Stoke-on-trent
ST4 6QG
United Kingdom
Prescot
L35 5DR
United Kingdom
Dafen
Llanelli
SA14 8QF
United Kingdom
Aberdeen
AB25 2ZN
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Caradoc Road
Aberystwyth
SY23 1ER
United Kingdom
Dryburn Hospital
North Road
Durham
DH1 5TW
United Kingdom
Carmarthen
SA31 2AF
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Airdrie
ML6 0JS
United Kingdom
Liverpool Road
Chester
CH2 1UL
United Kingdom
Harrow
HA1 3UJ
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Truro
TR1 3LJ
United Kingdom
Glasgow
G4 0SF
United Kingdom
Leicester
LE1 5WW
United Kingdom
Taunton
TA1 5DA
United Kingdom
Folkestone
CT19 5BN
United Kingdom
Leeds
LS1 3EX
United Kingdom
Edgbaston
Birmingham
B15 2GW
United Kingdom
Arrowe Park Road
Wirral
CH49 5PE
United Kingdom
Dundee
DD1 9SY
United Kingdom
Luton
LU4 0DZ
United Kingdom
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Stockton-on-tees
TS19 8PE
United Kingdom
Huddersfield Road
Halifax
HX3 0PW
United Kingdom
Watford
WD18 0HB
United Kingdom
Carlisle
CA2 7HY
United Kingdom
Sherriff Hill
Gateshead
NE9 6SX
United Kingdom
Williams Avenue
Dorchester
DT1 2JY
United Kingdom
London
W6 8RF
United Kingdom
East Kilbride
G75 8RG
United Kingdom
Cramlington
NE23 6NZ
United Kingdom
Antrim
BT41 2RL
United Kingdom
Doncaster
DN2 5LT
United Kingdom
York
YO31 8HE
United Kingdom
Salford
M6 8HD
United Kingdom
Wrythe Lane
Carshalton
SM5 1AA
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Sponsor information
University/education
Research and Innovation
East Atrium
Jubilee Conference Centre
Triumph Road
Nottingham
NG8 1DH
England
United Kingdom
| Phone | +44 (0)115 8467906 |
|---|---|
| angela.shone@nottingham.ac.uk | |
| Website | https://www.nottingham.ac.uk/fabs/research-innovation/meettheteam/angela.shone |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/05/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. The research findings will be disseminated via oral presentation at national and international meetings. The documents are not available yet but the researchers' policy is always to publish the protocol and statistical analysis plan. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Christine Roffe (christine.roffe@uhnm.nhs.uk) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.4 | 06/03/2023 | 15/03/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
18/10/2024: The following changes were made:
1. Frimley Park Hospital, Royal Surrey County Hospital, Royal Preston Hospital, University Hospital of Wales, Wycombe General Hospital, St Richard’s Hospital, Yeovil District Hospital, Hinchingbrooke Hospital, Princess Royal University Hospital, Torbay Hospital, Worthing Hospital, Peterborough City Hospital were removed from the study participating centres.
2. The overall study end date was changed from 31/07/2025 to 31/05/2027.
3. The target number of participants was changed from 1200 to 2100.
4. The recruitment end date was changed from 31/10/2024 to 31/10/2026.
5. The following study centre sites were added: Royal Stoke University Hospital, Whiston Hospital, Prince Philip Hospital, Aberdeen Royal Infirmary, Sunderland Royal Hospital, Bronglais General Hospital, University Hospital of North Durham, West Wales General Hospital, Royal Devon and Exeter Hospital, Norfolk and Norwich Hospital, Monklands District General Hospital, Countess of Chester Hospital, Northwick Park Hospital, New Cross Hospital, Southampton General Hospital, Royal Cornwall Hospital, Glasgow Royal Infirmary, Leicester Royal Infirmary, Musgrove Park Hospital, Royal Victoria Hospital, Leeds General Infirmary, Queen Elizabeth Hospital, Arrowe Park Hospital, Ninewells Hospital, Luton and Dunstable University Hospital, Royal Derby Hospital, North Tees and Hartlepool Hospital, Calderdale Royal Hospital, Watford General Hospital, Cumberland Infirmary, Queen Elizabeth Hospital (Gateshead), Dorset County Hospital, Charing Cross Hospital, Hairmyres Hospital, Northumbria Specialist Emergency Care Hospital, Antrim Area Hospital, Doncaster Royal Infirmary, York District Hospital, Salford Royal, St Helier Hospital, and Bradford Royal Infirmary.
04/04/2024: The following changes were made to the trial record:
1. The inclusion criteria were changed.
2. The recruitment start date was changed from 01/06/2024 to 31/10/2024.
3. The study participating centre Royal United Hospital Bath was removed.
15/03/2023: Protocol uploaded (not peer reviewed).
14/03/2023: The inclusion criteria were updated.
12/01/2022: The recruitment start date was changed from 31/01/2022 to 28/02/2022.
08/12/2021: Ethics approval details added. The recruitment start date was changed from 20/12/2021 to 31/01/2022.
08/11/2021: The recruitment start date was changed from 01/11/2021 to 20/12/2021.
12/10/2021: The following changes have been made:
1. The recruitment start date has been changed from 01/10/2021 to 01/11/2021.
2. The pending ethics approval has been added.
17/08/2021: The following changes have been made:
1. The EudraCT number has been added.
2. The trial website has been added.
10/08/2021: The recruitment start date was changed from 01/08/2021 to 01/10/2021.
17/06/2021: Trial's existence confirmed by the NIHR.
