Acute stroke treatment in the ambulance with a nitroglycerin patch

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 June 2021

Who is funding the study?
Dutch Heart Foundation (Netherlands)

Who is the main contact?
Miss Sophie van den Berg

Study website

http://www.mrasap.nl

Type

Scientific

Contact name

Miss Sophie van den Berg

ORCID ID

Contact details

Academisch Medisch Centrum
Meiberglaan 9
Amsterdam
1105AZ
Netherlands

EudraCT/CTIS number

2016-005086-31

IRAS number

ClinicalTrials.gov number

Protocol/serial number

60258

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(s)

Institutional review board of the Erasmus Medical Center, 19/10/2017, ref: MEC-2017-369

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

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

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

Overall study end date

24/06/2021

Reason abandoned (if study stopped)

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(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

1400

Total final enrolment

325

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

04/04/2018

Recruitment end date

31/10/2021

Countries of recruitment

Netherlands

Study participating centre

Academic Medical Center
Amsterdam
1105AZ
Netherlands

Study participating centre

University Medical Center (lead centre)
Utrecht
-
Netherlands

Study participating centre

Isala, Zwolle
-
Netherlands

Study participating centre

VU University Medical Center
Amsterdam
-
Netherlands

Study participating centre

OLVG-West
Amsterdam
-
Netherlands

Study participating centre

MC Slotervaart
Amsterdam
-
Netherlands

Study participating centre

Waterland Hospital
Purmerend
-
Netherlands

Study participating centre

St. Antonius Hospital
Nieuwegein
-
Netherlands

Study participating centre

Meander Medical Center
Amersfoort
-
Netherlands

Study participating centre

Diakonessenhuis
Utrecht
-
Netherlands

Organisation

University Medical Center Utrecht

Sponsor details

Heidelberglaan 100
Utrecht
3584CX
Netherlands

Sponsor type

Hospital/treatment centre

Website

ROR

https://ror.org/0575yy874

Funder type

Charity

Funder name

Dutch Heart Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

Intention to publish date

30/04/2023

Individual participant data (IPD) sharing plan

The data sharing plans for the current study are unknown and will be made available at a later date.

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs