Plain English Summary
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 April 2022
Who is funding the study?
Dutch Heart Foundation (Netherlands)
Who is the main contact?
Miss Sophie van den Berg
Trial website
Additional identifiers
EudraCT number
2016-005086-31
ClinicalTrials.gov number
Protocol/serial number
60258
Study information
Scientific title
Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch
Acronym
MR ASAP
Study hypothesis
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
Institutional review board of the Erasmus Medical Center, 19/10/2017, ref: MEC-2017-369
Study design
Multicentre prospective randomised open-label clinical trial with blinded endpoint assessment (PROBE design)
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
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
Phase
Phase III
Drug names
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 trial start date
01/05/2017
Overall trial end date
30/04/2022
Reason abandoned (if study stopped)
Eligibility
Participant 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)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1400
Participant 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)
Recruitment start date
01/01/2018
Recruitment end date
31/10/2021
Locations
Countries of recruitment
Netherlands
Trial participating centre
Academic Medical Center
Amsterdam
1105AZ
Netherlands
Trial participating centre
University Medical Center (lead centre)
Utrecht
-
Netherlands
Trial participating centre
Isala, Zwolle
-
Netherlands
Trial participating centre
VU University Medical Center
Amsterdam
-
Netherlands
Trial participating centre
OLVG-West
Amsterdam
-
Netherlands
Trial participating centre
MC Slotervaart
Amsterdam
-
Netherlands
Trial participating centre
Waterland Hospital
Purmerend
-
Netherlands
Trial participating centre
St. Antonius Hospital
Nieuwegein
-
Netherlands
Trial participating centre
Meander Medical Center
Amersfoort
-
Netherlands
Trial participating centre
Diakonessenhuis
Utrecht
-
Netherlands
Funders
Funder type
Charity
Funder name
Dutch Heart Foundation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal.
IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
30/04/2023
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
2019 protocol in https://www.ncbi.nlm.nih.gov/pubmed/31242931 (added 28/06/2019)