Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source (RE-SPECT ESUS)

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Stroke; Secondary Prevention

Treatments: Drug: dabigatran etexilate; Drug: ASA 100 mg; Drug: placebo to dabigatran etexilate; Drug: placebo to ASA; Drug: optional ASA as comedication; Drug: placebo to optional ASA as comedication

Study type: Interventional

Funder types: Industry

Identifiers

NCT02239120

1160.189

2013-003444-24 (EudraCT Number)

Details and patient eligibility

About

This trial will enroll approximately 6,000 patients with recent embolic stroke of unknown source (ESUS). Patients will be randomized to dabigatran or acetylsalicyclic acid (ASA) (1:1 ratio) and have visits every three months. The study doctor may prescribe blinded concomitant ASA for pts with coronary artery disease but this is not mandatory. All Adverse Events (AEs), Serious Adverse Events (SAEs), outcome events will be recorded. The trial will conclude when the required number of stroke events are positively adjudicated which is estimated to take 3 years (including 2.5 years of enrollment).

Enrollment: 5,390 patients

Sex: All

Ages: 18 to 150 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Ischemic stroke with a brain lesion visualized by neuroimaging (either brain Computed Tomography (CT) or Magnetic Resonance Image (MRI)). The visualized stroke is a non-lacunar infarct , e.g. involving the cortex or >1.5 cm (>2.0 cm if measured on MRI diffusion-weighted images) in largest diameter if exclusively subcortical.Visualization by CT usually requires delayed imaging >24-48 hours after stroke onset.
• The index stroke must have occurred either up to 3 months before randomization (Modified Rankin Scale(mRS) <=3 at randomization) or up to 6 months before randomization (mRS <=3 at randomization) in selected patients that are >= 60 years plus at least one additional risk factor for recurrent stroke.
• Arterial imaging or cervical plus Transcranial Doppler (TCD) ultrasonography does not show extra-cranial or intracranial atherosclerosis with >= 50% luminal stenosis in artery supplying the area of acute ischemia.
• As evidenced by cardiac monitoring for >= 20 hours with automated rhythm detection, there is absence of AF > 6 minutes in duration (within a 20 hour period, either as single episode or cumulative time of multiple episodes).

Further inclusion criteria apply.

Exclusion criteria

• Modified Rankin Scale of >=4 at time of randomization or inability to swallow medications.
• Major risk cardioembolic source of embolism such as: a) intracardiac thrombus as evidenced by transthoracic or transesophageal echocardiography, b) paroxysmal, persistent or permanent Atrial fibrillation (AF), c) atrial flutter, d) prosthetic cardiac valve (mitral or aortic, bioprosthetic or mechanical), e) atrial myxoma, f) other cardiac tumors, g) moderate or severe mitral stenosis, h) recent (< 4weeks) myocardial infarction, i) valvular vegetations, or j) infective endocarditis.
• Any indication that requires treatment with an anticoagulant as per Investigator's judgment.
• History of atrial fibrillation (unless it was due to reversible causes such as hyperthyroidism or binge drinking, and has been permanently resolved).
• Other specific stroke etiology (i.e. cerebral arteritis or arterial dissection, migraine with aura/vasospasm, drug abuse).
• Renal impairment with estimated creatinine clearance (as calculated by Cockcroft-Gault equation) <30mL/min at screening, or where Investigator expects creatinine clearance is likely to drop below 30mL/min during the course of the study.

Further exclusion criteria apply.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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5,390 participants in 2 patient groups

dabigatran etexilate 110 or 150 mg

Experimental group

Description:

Patients will be assigned Dabigatran 150 mg b.i.d. (unless they are 75 years or older, or have a Creatinine Clearance (CrCl) of greater than or equal to 30 to less than 50ml/min (or experience GI bleed during trial), in which case they will receive Dabigatran 110 mg b.i.d.). All patients in this arm will also receive ASA placebo (q.d.)

Treatment:

Drug: optional ASA as comedication

Drug: placebo to ASA

Drug: dabigatran etexilate

ASA 100 mg

Active Comparator group

Description:

All patients will receive blinded ASA 100 mg q.d. and dabigatran placebo 150 mg b.i.d. (unless they are 75 years or older, or have a CrCl of greater than or equal to 30 to less than 50ml/min (or experience GI bleed during trial), in which case they will receive placebo Dabigatran 110 mg b.i.d

Treatment:

Drug: placebo to optional ASA as comedication

Drug: placebo to dabigatran etexilate

Drug: ASA 100 mg