Dabigatran Following Transient Ischemic Attack and Minor Stroke (DATAS II)

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.

Study Overview

• Status: Completed
• Conditions: Transient Ischemic Attack; Minor Ischemic Stroke
• Intervention / Treatment: Drug: Dabigatran; Drug: Acetylsalicylic acid

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
    • Edmonton, Alberta, Canada, T6L 5X8
      • Grey Nuns Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Stroke Program
  • Ontario
    • Hamilton, Ontario, Canada, L8L 0A6
      • Hamilton Health Sciences
  • Quebec
    • Montréal, Quebec, Canada, H2L 4M1
      • Centre Hospitalier De L'Universite De Montreal, Hopital Notre-Dame

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran therapy; 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)	Drug: Dabigatran; Dabigatran will be taken bid for 30 days post enrolment. The dose of dabigatran will be based on patient age and renal function.; Other Names: Pradax (Canada)/ Pradaxa (USA and rest of world)
Active Comparator: Acetylsalicylic Acid thereapy; 325 mg loading dose then 81 mg/day for 30 days	Drug: Acetylsalicylic acid; participants randomized to ASA therapy will be loaded with 325 mg of ASA, followed by 81 mg/day; Other Names: Aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of symptomatic hemorrhagic transformation	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.	within 5 weeks of treatment initiation

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of asymtomatic hemorrhagic transformation	day 30

Collaborators and Investigators

• Sponsor: University of Alberta

Publications and helpful links

General Publications

• Butcher KS, Ng K, Sheridan P, Field TS, Coutts SB, Siddiqui M, Gioia LC, Buck B, Hill MD, Miller J, Klahr AC, Sivakumar L, Benavente OR, Hart RG, Sharma M. Dabigatran Treatment of Acute Noncardioembolic Ischemic Stroke. Stroke. 2020 Apr;51(4):1190-1198. doi: 10.1161/STROKEAHA.119.027569. Epub 2020 Feb 26.
• Ng KH, Sharma M, Benavente O, Gioia L, Field TS, Hill MD, Coutts SB, Butcher K; DATAS-2 Investigators. Dabigatran following acute transient ischemic attack and minor stroke II (DATAS II). Int J Stroke. 2017 Oct;12(8):910-914. doi: 10.1177/1747493017711947. Epub 2017 Jun 6.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): December 18, 2018
• Study Completion (Actual): December 18, 2018

Study Registration Dates

• First Submitted: November 17, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 20, 2014

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 28, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Ischemic Stroke; Ischemia; Ischemic Attack, Transient; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Dabigatran
• Other Study ID Numbers: DATAS002