Acute stroke treatment in the ambulance with a nitroglycerin patch
| ISRCTN | ISRCTN99503308 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN99503308 |
| EudraCT/CTIS number | 2016-005086-31 |
| Secondary identifying numbers | 60258 |
- Submission date
- 31/10/2017
- Registration date
- 02/01/2018
- Last edited
- 13/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Stroke is a life-threatening medical condition, caused by a disorder in the blood supply to the brain. There are two main types of stroke: ischaemic, caused by a reduction in blood flow, or haemorrhagic, caused by a rupture of an artery in the brain. Within minutes, brain cells die. Symptoms can vary from limb weakness, drooping of the face or speech difficulties. Prompt treatment is crucial and early action can reduce brain damage and complications. This study investigates the treatment of stroke with an adhesive patch containing the medicine nitroglycerin. Nitroglycerin is a medication that is commonly administered as heart medication but it could help if applied quickly after a stroke as it can help lower blood pressure and open up blood vessels. This patch will be given in the ambulance by the paramedic to patients with suspected stroke (brain infarct or bleeding). Recent research suggests a beneficial effect of the treatment with this drug in patients with acute stroke, if given within the first few hours. The aim of this study is to find out if treatment with a nitroglycerin patch will lead to better functional outcome at 90 days.
Who can participate?
Adult patients with suspected stroke with symptom onset within 3 hours and a systolic blood pressure of 140 and higher can participate.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive the standard care. Those in the second group receive a transdermal nitroglycerin patch with a dosage of 5 mg/24 hours to wear plus standard care. The patch is applied by a paramedic in the pre-hospital setting and continued during hospital admission for a total of 24 hours. During hospital admission, no extra tests or investigations will be performed. At 90 days, participants receive a phone call to assess the outcomes of the patch.
What are the possible benefits and risks of participating?
The possible benefit of this treatment is a better functional outcome. This will be measured during a telephone follow-up after 3 months. The possible risks of participating are the side effects of the medication. Nitroglycerin has been used for decades in heart disease and is most often well tolerated. The most common side effects are headache, nausea and low blood pressure.
Where is the study run from?
This study is run from the University Medical Center Utrecht (Netherlands) and the Academic Medical Center in Amsterdam (Netherlands).
When is the study starting and how long is it expected to run for?
May 2017 to June 2021
Who is funding the study?
Dutch Heart Foundation (Netherlands)
Who is the main contact?
Miss Sophie van den Berg
Contact information
Scientific
Academisch Medisch Centrum
Meiberglaan 9
Amsterdam
1105AZ
Netherlands
Study information
| Study design | Multicentre prospective randomized open-label clinical trial with blinded endpoint assessment (PROBE design) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch |
| Study acronym | MR ASAP |
| Study objectives | Prehospital treatment with a transdermal nitroglycerin patch, applied within 3 hours after stroke onset, improves functional outcome at 90 days in patients with acute ischaemic stroke or intracerebral haemorrhage. |
| Ethics approval(s) | Institutional review board of the Erasmus Medical Center, 19/10/2017, ref: MEC-2017-369 |
| Health condition(s) or problem(s) studied | Acute ischaemic stroke and intracerebral haemorrhage |
| Intervention | Participants are randomly assigned in a 1:1 ratio by a web-based randomisation to one of two groups. Those in the first group receive the standard care. Those in the second group receive a transdermal nitroglycerin patch with a dosage of 5 mg/24 hours to wear plus standard care. The patch is applied by a paramedic in the prehospital setting and continued during hospital admission for a total of 24 hours. During hospital admission, no extra tests or investigations will be performed. At 90 days, a telephone interview is performed by a blinded outcome assessor to assess the outcomes of the patch. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Glyceryl trinitrate |
| Primary outcome measure | Functional outcome is assessed using the modified Rankin Scale (mRS) at 90 days. |
| Secondary outcome measures | 1. At hospital admission: 1.1. Vital signs (blood pressure and heart rate) 1.2. Collateral circulation assessed with CT-angiography 2. At 24 hours: 2.1. Treatment with intravenous thrombolysis and/or endovascular treatment 2.2. Vital signs (blood pressure and heart rate) 2.3. Neurological deficit assessed using the National Institutes of Health Stroke Scale (NIHSS) 3. At 90 days, assessed during a blinded telephone interview: 3.1. Death 3.2. Dichotomised mRS (0-1 vs. 2-6; 0-2 vs. 3-6; 0-3 vs. 4-6) 3.3. Disability assessed with the score on the Barthel Index 3.4. Quality of life assessed with the EuroQol-5D-5L 3.5. Home time and patient location over the first 90 days |
| Overall study start date | 01/05/2017 |
| Completion date | 24/06/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1400 |
| Total final enrolment | 325 |
| Key inclusion criteria | 1. Age 18 years or older 2. Probable diagnosis of acute stroke, as assessed by the paramedic in the prehospital setting 3. Score of 2 or 3 on the Face Arm Speech Test (FAST) 4. Systolic blood pressure ≥ 140 mm Hg 5. Possibility to start the trial treatment within 3 hours of symptom onset 6. Intention to transport the patient to one of the participating hospitals 7. Written informed consent (deferred) |
| Key exclusion criteria | 1. Considerable pre-stroke dependency in activities of daily living, defined as staying in a chronic nursing home or rehabilitation centre 2. Known pregnancy or lactation 3. Indication for acute treatment with nitroglycerin or known use of nitroglycerin in the previous 12 hours 4. Indication for acute reduction of blood pressure 5. Known hypersensitivity to GTN, nitrates in general, or the adhesives used in the patch 6. Glasgow Coma Scale < 8 7. Known with any of the following heart disorders: myocardial insufficiency due to obstruction; aortic or mitral valve stenosis; constrictive pericarditis; hypertrophic obstructive cardiomyopathy; cardiac tamponade 8. Known marked anaemia, defined as haemoglobin < 5 mmol/L 9. Known closed angle glaucoma 10. Known concomitant use of phosphodiesterase type-5 inhibitors, (e.g. sildenafil, tadalafil, vardenafil) |
| Date of first enrolment | 04/04/2018 |
| Date of final enrolment | 31/10/2021 |
Locations
Countries of recruitment
- Netherlands
Study participating centres
1105AZ
Netherlands
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Netherlands
Netherlands
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Netherlands
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Netherlands
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Netherlands
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Netherlands
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Netherlands
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Netherlands
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Netherlands
Sponsor information
Hospital/treatment centre
Heidelberglaan 100
Utrecht
3584CX
Netherlands
"ROR" |
https://ror.org/0575yy874 |
|---|
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | 30/04/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 26/06/2019 | 28/06/2019 | Yes | No |
| Results article | 01/09/2022 | 05/09/2022 | Yes | No | |
| Abstract results | 22/05/2019 | 13/02/2024 | No | No | |
| Abstract results | 01/09/2021 | 13/02/2024 | No | No | |
| Abstract results | 03/05/2022 | 13/02/2024 | No | No |
Editorial Notes
13/02/2024: Abstracts added.
05/09/2022: Publication reference added.
01/09/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/01/2018 to 04/04/2018.
2. Total final enrolment added.
3. The overall trial end date was changed from 30/04/2022 to 24/06/2021.
01/07/2020: Recruitment to this study is no longer paused.
24/04/2020: Due to current public health guidance, recruitment for this study has been paused.
28/06/2019: Publication reference added.
