Stopping or continuing blood thinners after stroke at young age without a known cause: STOP trial
| ISRCTN | ISRCTN96178713 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN96178713 |
| EudraCT/CTIS number | 2024-513092-40-00 |
| Secondary identifying numbers | 114180, ZonMw Subsidy decision on file number: 10140252210002 |
- Submission date
- 11/07/2024
- Registration date
- 17/09/2024
- Last edited
- 17/01/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
In the Netherlands, 100,000 patients live with the long-term consequences of a TIA or ischaemic stroke at a young age (18-49 years old). The majority of these patients will use lifelong blood thinners (for example clopidogrel). This treatment strategy is based on studies among people with stroke due to atherosclerosis, who were on average 65 years of age. It is unknown whether lifelong use of blood thinners is effective for young people with TIA or ischaemic stroke as it is in elderly people, particularly in patients without a known cause for their stroke (cryptogenic stroke). Yet, young patients are exposed to blood thinners for decades with an increased risk of serious bleeding. It has never been established whether the benefits of blood thinners outweigh the risks for young patients, particularly in patients without atherosclerosis. The STOP trial aims to investigate whether blood thinners can safely be stopped three or more years after a TIA or ischemic stroke without a known cause at a young age.
Who can participate?
Patients who had a TIA or ischaemic stroke at the age of 18-49 years, for which the treating neurologist did not find a cause. The TIA or ischaemic stroke should have taken place at least 3 years before inclusion and participation in the study and patients should not have experienced a recurrent stroke or myocardial infarction afterwards.
What does the study involve?
Patients are randomly allocated to two groups: group 1 stops taking blood thinners, and group 2 continues taking blood thinners. Patients are requested to fill in a questionnaire each year. The study will run for 5 years.
What are the possible benefits and risks of participating?
Patients who stop using blood thinners have a lower risk of serious bleeding complications. In addition, stopping antiplatelet therapy provides convenience for patients who don’t have to take daily antiplatelet medication.
Patients who continue to use blood thinners have a risk of serious bleeding (for example bleeding from the gut or even bleeding in the brain). We expect that the risk of a recurrent stroke or myocardial infarction is similar for patients who stop or continue blood thinners. However, there might be a very small increased risk of a recurrent stroke or myocardial infarction among patients who stop blood thinners.
Where is the study run from?
The Radboud University Medical Center Nijmegen, the Netherlands
When is the study starting and how long is it expected to run for?
Recruitment is planned to start in october 2024 and run for two years
Who is funding the study?
The Netherlands Organisation for Health Research and Development
Who is the main contact?
Prof. Frank-Erik de Leeuw, FrankErik.deLeeuw@radboudumc.nl
Contact information
Public, Scientific, Principal Investigator
Geert Grooteplein Zuid 10
Nijmegen
6500 HB
Netherlands
 ORCID ID |
0000-0003-2221-3026 |
|---|---|
| Phone | +31243098289 |
| FrankErik.deLeeuw@radboudumc.nl |
Study information
| Study design | Multicenter randomized non-inferiority trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment, Safety |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Stopping or continuing platelet inhibitors after cryptogenic stroke at young age: STOP trial |
| Study acronym | STOP trial |
| Study objectives | Discontinuaton of antiplatelet drugs is non-inferior to continuation of antiplatelet durgs, three or more years after a cryptogenic stroke at young age |
| Ethics approval(s) |
Approved 14/11/2024, METC Oost Nederland (Geert Grooteplein Zuid 10, Nijmegen, 6500 HB, Netherlands; +31243613154; metcoost-en-cmo@radboudumc.nl), ref: None provided |
| Health condition(s) or problem(s) studied | Patients with cryptogenic stroke at the age of 18-49 years |
| Intervention | Discontinuation of antiplatelet therapy. The intervention is the discontinuation of oral daily antiplatelet therapy (clopidogrel 75mg once daily or acetylsalicylic acid 80mg once daily, with or without dipyridamole 200mg twice daily). The comparator is the continuation of antiplatelet therapy according to standard care. There is no specific trial drug manufacturer. Patients will be randomly allocated 1:1 by an external web-based system to the intervention or comparator arm. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Clopidogrel, acetylsalicylic acid, dipyridamole |
| Primary outcome measure | Primary efficacy outcome: 1. A composite endpoint of major vascular events, defined as TIA with imaging confirmation, stroke, myocardial infarction, or death from vascular causes measured using a digital questionnaire or telephone follow-up and verified with medical records with annual follow-up for five years Primary safety outcome: 2. Major bleeding, according to the International Society for Thrombosis and Haemostasis criteria, measured using a digital questionnaire or telephone follow-up and verified with medical records with annual follow-up for five years |
| Secondary outcome measures | The following secondary outcome measures are assessed using digital questionnaires or telephone follow-up with annual follow-up for five years: 1. Disability measured using the modified Ranking Scale 2. Quality of life measured using EQ-5D-5L 3. All cause mortality |
| Overall study start date | 01/04/2024 |
| Completion date | 01/11/2032 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 1316 |
| Key inclusion criteria | 1. First ever ischaemic stroke, or TIA with evidence of ischaemia on imaging, 3-10 years before study participation 2. Age 18-49 years old at the time of TIA/ischaemic stroke 3. Cryptogenic aetiology, defined as no other aetiology after standard work-up according to national and international guidelines for young stroke (imaging of the brain (CT-scan or MRI-scan) and cervical arteries (CTA, MRA or carotid ultrasound), routine blood tests (complete blood count, erythrocyte sedimentation rate, CRP, antiphospholipid antibodies, ECG, at least 24 hours cardiac rhythm monitoring and transthoracic/transesophageal echocardiography). |
| Key exclusion criteria | 1. History of MI, coronary revascularisation or documented peripheral arterial disease 2. Other indication for antiplatelet therapy 3. Indication for oral anticoagulants or low molecular weight heparin 4. Recurrent ischaemic event at any time after the index event 5. Any stenosis of intracranial or cervical artery at time of stroke 6. Two or more risk factors for atherosclerotic disease prior to the index event, according to the following definitions: 6.1. Arterial hypertension (treated or known blood pressure before stroke >140/90 mm Hg) 6.2. Diabetes mellitus (treated or known blood fasting glucose >7 mmol/l) 6.3. Current smoking (or smoking stopped within the last 6 months) 6.4. Hypercholesterolaemia (treated or known low-density lipoprotein before the stroke >160 mg/dl or 4, mmol/l) 7. Any condition that prevents long-term follow-up |
| Date of first enrolment | 23/12/2024 |
| Date of final enrolment | 01/10/2026 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Nijmegen
6500 HB
Netherlands
Sponsor information
Hospital/treatment centre
Clinical Research Policies, Geert Grooteplein Zuid 10
Nijmegen
6500 HB
Netherlands
| Phone | +3124 36 1489 |
|---|---|
| integraalkwaliteitssysteemwetenschappelijkonderzoek@radboudumc.nl | |
| Website | https://www.radboudumc.nl/EN/Pages/default.aspx |
"ROR" |
https://ror.org/05wg1m734 |
Funders
Funder type
Research organisation
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- Netherlands Organisation for Health Research and Development
- Location
- Netherlands
Results and Publications
| Intention to publish date | 01/11/2033 |
|---|---|
| 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 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 |
Editorial Notes
17/01/2025: The recruitment start date was changed from 01/10/2024 to 23/12/2024.
16/07/2024: Study's existence confirmed by ZonMw.
