Dabigatran Following Transient Ischemic Attack and Minor Stroke

Transient Ischemic Attack Clinical Trial

— DATAS II  

Official title:

Dabigatran Following Transient Ischemic Attack and Minor Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02295826
• Other study ID #: DATAS002
• Status: Completed
• Phase: Phase 2
• Start date: January 2015
• Est. completion date: December 18, 2018

Study information

• Verified date: October 2018
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: December 18, 2018
• Est. primary completion date: December 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ischemia
• Ischemic Attack, Transient
• Minor Ischemic Stroke
• Stroke
• Transient Ischemic Attack

Intervention

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

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Grey Nuns Hospital	Edmonton	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame	Montréal	Quebec
Canada	Vancouver Stroke Program	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of asymtomatic hemorrhagic transformation		day 30