Dabigatran Following Transient Ischemic Attack and Minor Stroke

Phase 2

Completed

• Conditions: Transient Ischemic Attack; Minor Ischemic Stroke
• Interventions: Drug: Acetylsalicylic acid; Drug: Dabigatran

• Registration Number: NCT02295826
• Lead Sponsor: University of Alberta

Brief Summary

Rationale: To date, anticoagulant therapy in acute stroke has also been limited by excess hemorrhagic events. The oral anticoagulant dabigatran is a novel agent, which has been shown to be associated with much lower intracranial hemorrhage rates. It has been suggested that this agent may provide the superior benefits of anticoagulation in acute stroke, without the concomitant increase in hemorrhage risk associated with heparin/LMWH or warfarin.

Study Design: DATAS II is a randomized, open label blinded endpoint trial. Participants (n=300) with TIA or ischemic stroke (NIHSS score \<9) will be enrolled within 48 hours of symptom onset from approximately four (4) health care centres across Canada. All participants will have an MRI with DWI lesion volume \< 25 ml. Participants will be randomized 1:1 to treatment with dabigatran for 30 days or ASA 81 mg daily (current standard of care). All stroke patients will initially be screened with a non-contrast CT scan of the brain. The first MRI will be performed within 48 hours of symptom onset. Imaging studies will be repeated at day 30. All patients will be assessed clinically at Day 30 and Day 90.

Study Aims:

1. Establish the safety of early anticoagulation with the novel oral anticoagulant dabigatran in acute cerebrovascular syndrome patients.

2. Identify the rate of both symptomatic and asymptomatic hemorrhagic transformation (HT) associated with these treatments.

3. Identify predictors of HT associated with acute dabigatran treatment.

Hypothesis: The Investigators hypothesize that symptomatic HT rates in dabigatran and ASA treated patients will not be significantly different.

Study outcomes: The primary outcome is the rate of symptomatic hemorrhagic transformation (HT), defined as a parenchymal hematoma, which is \>30% of the infarcted area on DWI, with substantial space- occupying effect, associated with clinical worsening (≥4 point increase in National Institutes of Health Stroke Scale (NIHSS) score) within 5 weeks of treatment initiation. The major secondary outcome the rate of asymtomatic HT see on day 30 MRI sequence.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-17
• Study First Submitted QC: 2014-11-17
• Study First Posted: 2014-11-20
• Study Start: 2015-01
• Status Verified: 2018-10
• Primary Completion: 2018-12-18
• Study Completion: 2018-12-18
• Last Update Submitted: 2019-01-28
• Last Update Posted: 2019-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Male or female patients
2. Must be >18 years of age
3. Must have TIA or ischemic stroke (NIHSS score <9 - see section 2.7 for further clarification)
4. Symptom onset is < 72 hours prior to enrollment or Study therapy must initiated within 48 hours of symptom onset (in case where onset time cannot be established, it will be considered to be the time when the patient was lst know to be well
5. Informed consent must be obtained from either the patient or substitute decision maker (according to local REB policy) prior to any study related procedures being performed
6. All patients will have a MRI including DWI prior to randomization
7. DWI lesion volume must be <25ml
8. Patients without DWI lesions, but a clinical history considered consistent with TIA, determined by the attending physician, can be included

Exclusion Criteria

1. Patients with stroke mimics - such as seizures, migraine etc
2. Patients with contraindications to MRI including metallic implants
3. Patients with any past sensitivity to gadolinium contrast media will be eligible, but will not undergo PWI or contrast enhanced MRA (both optional sequences)
4. Patients with renal failure defined as Glomerular Filtration Rate (GFR) < 30 ml/min
5. Patients deemed, as attending stroke physician, to have any ongoing bleeding risks or unsuitable for dabigatran therapy
6. Patients with MRI demonstrated additional pathology including arteriovenous malformations, intracranial aneurysms, tumors or abscess, which potentially increase the rise of bleed. Individuals with small incidental leasions, at low risk of bleed such as meningiomas may be included at the discretion of the investigator.
7. Patients with an acute DWI lesion volume of >25 ml (DWI volume to be estimated using the ABC/2 technique 110)**
8. Age <18 years
9. Pregnant or breast feeding women.
10. Severe dysphagia necessitating naso-gastric (NG) feeding (dabigatran can not be delivered via NG tube)
11. Planned thrombolysis or endovascular intervention for the index event
12. Thrombolysis for ischemic stroke within the preceding 7 days
13. Planned carotid endarterectomy/carotid artery stent within 30 days Note: Carotid Investigations will be completed prior to enrolment. Patients with symptomatic stenoses and a planned carotid procedure will be excluded.
14. Any history of spontaneous intracranial bleeding
15. Clear indication for anticoagulation, including atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state
16. Co-morbid illness with expected life expectancy of <90 days

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acetylsalicylic Acid thereapy	Acetylsalicylic acid	325 mg loading dose then 81 mg/day for 30 days
Dabigatran therapy	Dabigatran	150 mg BID for 30 days (dose modification - reduced to 110mg BID in patients \>80 years of age and/or an eGFR of 30-50 ml/min)

Primary Outcome Measures

Name	Time	Method
Rate of symptomatic hemorrhagic transformation	within 5 weeks of treatment initiation	The primary endpoint is the rate of symptomatic hemorrhagic transformation (HT), defined as a parenchymal hematoma, which is \>30% of the infarcted area on DWI, with substantial space-occupying effect, associated with clinical worsening (≥4 point increase in National Institutes of Health Stroke Scale (NIHSS) score) within 5 weeks of treatment initiation.

Secondary Outcome Measures

Name	Time	Method
Rate of asymtomatic hemorrhagic transformation	day 30

Trial Locations

Locations (6)

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Grey Nuns Hospital; 🇨🇦 Edmonton, Alberta, Canada

Vancouver Stroke Program; 🇨🇦 Vancouver, British Columbia, Canada

Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame; 🇨🇦 Montréal, Quebec, Canada