Dabigatran Following Transient Ischemic Attack and Minor Stroke

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.

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Key information

Conditions

Transient Ischemic Attack Brain Diseases Brain Ischemia Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Ischemic Attack, Transient Minor Ischemic Stroke Nervous System Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Calgary, Calgary, Alberta, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Male or female patients
Must be >18 years of age
Must have TIA or ischemic stroke (NIHSS score <9 - see section 2.7 for further clarification)
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
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
All patients will have a MRI including DWI prior to randomization
DWI lesion volume must be <25ml
Patients without DWI lesions, but a clinical history considered consistent with TIA, determined by the attending physician, can be included

Exclusion criteria

Patients with stroke mimics - such as seizures, migraine etc
Patients with contraindications to MRI including metallic implants
Patients with any past sensitivity to gadolinium contrast media will be eligible, but will not undergo PWI or contrast enhanced MRA (both optional sequences)
Patients with renal failure defined as Glomerular Filtration Rate (GFR) < 30 ml/min
Patients deemed, as attending stroke physician, to have any ongoing bleeding risks or unsuitable for dabigatran therapy
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.
Patients with an acute DWI lesion volume of >25 ml (DWI volume to be estimated using the ABC/2 technique 110)**
Age <18 years
Pregnant or breast feeding women.
Severe dysphagia necessitating naso-gastric (NG) feeding (dabigatran can not be delivered via NG tube)
Planned thrombolysis or endovascular intervention for the index event
Thrombolysis for ischemic stroke within the preceding 7 days
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.
Any history of spontaneous intracranial bleeding
Clear indication for anticoagulation, including atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state
Co-morbid illness with expected life expectancy of <90 days

Treatment and study plan

dabigatran

Drug

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)

acetylsalicylic acid

Drug

participants randomized to ASA therapy will be loaded with 325 mg of ASA, followed by 81 mg/day

Other names: Aspirin

Primary outcomes

Rate of symptomatic hemorrhagic transformation

Time frame: 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 outcomes

Rate of asymtomatic hemorrhagic transformation

Time frame: day 30

Sponsors and collaborators

Lead sponsor

University of Alberta

Other

Registry information

Acronym: DATAS II

Important dates

Study start: 2015
Primary completion: 2018
Study completion: 2018
First posted: Nov 20, 2014
Registry last updated: Jan 30, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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