Dabigatran Treatment Following Transient Ischemic Attack and Minor Stroke

NCT01769703 | Completed Phase 2 DMC

• 1 other identifier: DATAS
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: Demonstrate the safety of early use of dabigatran following TIA/minor stroke. Background: Although aggressive antithrombotic therapy has been shown to reduce the number of new ischemic events following stroke/TIA, this has always been offset by an increase in the risk of hemorrhagic transformation. Dabigatran is much safer than previously tested antithrombotic agents, with respect to intracranial bleeding and therefore offers a unique treatment opportunity in these high-risk patients. TIA/minor stroke represent the largest group of cerebrovascular disease patients. A short-term intervention such as 30 days of dabigatran treatment has the potential for a very large impact from the population health perspective, given the number of patients who may be treated if a benefit can be demonstrated. Study design: This is an open label, single arm study. Patients with TIA/minor stroke (National Institutes of Health Stroke Scale (NIHSS) score \</=3) who can be treated within 24 hours of symptom onset will be eligible. All patients will be treated with dabigatran for 30 days. The dose of dabigatran will be determined by age and renal function (patients \>80 years old and/or with GFR 30-50 ml/min will received 110 mg bid, and all other patients will receive 150 mg BID).The primary endpoint is symptomatic hemorrhagic transformation. Patients (n=50) with TIA/minor stroke, defined as having a National Institutes of Health Stroke Scale Score of \</=3, will undergo an MRI, including diffusion-weighted imaging (DWI), as well as gradient recall echo (GRE) sequences, which will be used to assess for hemorrhagic transformation. Patients will have a repeat MRI examination at 7 and 30 days to assess for hemorrhagic transformation and new lesion development. The primary endpoint of of phase I is symptomatic hemorrhagic transformation, defined as a parenchymal hematoma on the day 7 MRI scan (GRE sequence), associated with clinical worsening (\>/=4 point increase in National Institutes of Health Stroke Scale (NIHSS) score). If dabigatran can be used safely in this population, a second phase aimed at demonstrating the rate of new ischemic lesion development following TIA can be reduced with aggressive antithrombotic therapy. A randomized open-label, blinded endpoint evaluation design will be employed. The investigators hypothesize that dabigatran therapy administered within 24 hours of symptom onset will reduce the rate of new ischemic lesions, relative to standard care, one week and 30 days after onset.

Conditions

Transient Ischemic Attack; Minor Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• Symptomatic Hemorrhagic Transformation

  The primary endpoint of phase I is the cumulative incidence of symptomatic hemorrhagic transformation, defined as a parenchymal hematoma on the day 7 and day 30 MRI scans (GRE sequence), associated with clinical worsening (≥4 point increase in National Institutes of Health Stroke Scale (NIHSS) score).

  30 days post-treatment

Study Arms (1)

Dabigatran

EXPERIMENTAL

Drug: Dabigatran 110/150 mg BID

Interventions

Dabigatran 110/150 mg BID DRUG

Dabigatran will be taken bid for 30 days post enrolment. The dose of dabigatran will be based on patient age and renal function.

Also known as: Pradax (Canada)/ Pradaxa (USA and rest of world)

Dabigatran

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients included in the study will have TIA or minor stroke (defined as NIHSS score \</= 3).
• Patients must be treated within 24 hours of symptom onset. In cases where onset time cannot be established, it will be considered to be the time when the patient was last known to be well.
• All patients will be 18 years or older.
• All patients will have an MRI, with evidence of at least one DWI lesion, consistent with ischemia, prior to randomization.

You may not qualify if:

• Patients with stroke mimics (such as seizures, migraine etc.) will be excluded from the study.
• Patients with contraindications to MRI will also be excluded, including metallic implants.
• Patients with any past sensitivity to gadolinium contrast media will be eligible, but will not undergo PWI.
• Patients with renal failure, defined as Glomerular Filtration Rate (GFR) \<30 ml/min, will be excluded as well.
• Patients deemed to have any ongoing bleeding risks or unsuitable for dabigatran therapy by the attending stroke clinician will be ineligible.
• Patients in whom the MRI demonstrates additional pathology including arteriovenous malformations, intracranial aneurysms, tumours, or abscess will be excluded.
• Age \<18 years
• Planned thrombolysis or endovascular intervention for the index event
• Thrombolysis for ischemic stroke within preceding 7 days
• Planned carotid endarterectomy/carotid artery stent within 30 days
• 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 \<30 days

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G2B7, Canada

Location

Related Publications (1)

• Kate M, Gioia L, Buck B, Sivakumar L, Jeerakathil T, Shuaib A, Butcher K. Dabigatran Therapy in Acute Ischemic Stroke Patients Without Atrial Fibrillation. Stroke. 2015 Sep;46(9):2685-7. doi: 10.1161/STROKEAHA.115.010383. Epub 2015 Jul 30.

  PMID: 26304866 DERIVED

MeSH Terms

Conditions

Ischemic Attack, Transient

Interventions

Dabigatran; BID protein, human

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 24, 2012
• First Posted: January 17, 2013
• Study Start: February 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: October 30, 2014

Record last verified: 2014-10

Locations

CA (1)