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

Boehringer Ingelheim5,390 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

5,390

Conditions

Stroke Secondary Prevention

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 150 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Adjudicated Recurrent Stroke

Adjudicated recurrent stroke (ischemic, hemorrhagic, or unspecified) is presented. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: From randomisation until full follow up period, approximately 43 months.

First Major Bleed (Adjudicated)

First major bleed is primary safety endpoint. Major bleeds were defined according to the International Society of Thrombosis and Haemostasis (ISTH) definition as follows: * Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or, * Bleeding (which should be overt) associated with a reduction in haemoglobin of at least 2 grams/ decilitre (g/dL) (1.24 millimoles Per Litre (mmol/L)), or leading to transfusion of ≥2 units of blood or packed cells (equivalent to ≥4.5 units in Japan); the haemoglobin drop should be considered to be due to and temporally related to the bleeding event and/or, * Fatal bleed. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Secondary Outcomes

Adjudicated Ischaemic Stroke

Adjudicated ischaemic stroke is a key secondary endpoint. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: From randomisation until full follow up period, up to 43 months

Adjudicated Composite of Non-fatal Stroke, Non-fatal Myocardial Infarction, or Cardiovascular Death

Adjudicated composite of non-fatal stroke, non-fatal myocardial infarction (MI), or cardiovascular death is a key secondary endpoint. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: From randomisation until full follow up period, up to 43 months

Disabling Stroke

Disabling stroke (modified Rankin Scale greater than or equal to 4, as determined 3 months after recurrent stroke) is presented. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: From randomisation until full follow up period, up to 43 months

All-cause Death

All-cause death is presented. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: From randomisation until full follow up period, up to 43 months

Adjudicated Intracranial Hemorrhage

Adjudicated intracranial haemorrhage comprised the subtypes of intracerebral bleeds, intraventricular bleeds, subdural bleeds, epidural bleeds, and subarachnoid bleeds. Microbleeds did not qualify as intracranial haemorrhage, except when they were symptomatic. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Adjudicated Fatal Bleed

Adjudicated fatal bleeding was defined as a bleeding event which the Independent Event Adjudication Committee (IAC) determined as the primary cause of death or contributed directly to death. The annualised event rate represents the average number of events per patient during a 1-year period. Because there were 0 events in one treatment group, the hazard ratio is unable to be calculated.

Time frame: Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Adjudicated Life-threatening Bleed

Major bleeds were to be classified as life-threatening if they met one or more of the following criteria: fatal bleed, symptomatic intracranial bleed, reduction in haemoglobin of at least 5 grams/ deciliter (g/dL), transfusion of at least 4 units of packed red blood cells (equivalent to 9 units in Japan), associated with hypotension requiring the use of intravenous inotropic agents, or necessitated surgical intervention. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Any Bleed (Investigator-reported)

This was the sum of all major and minor bleeds (Minor bleeds were clinical bleeds that did not fulfil the criteria for major bleeds), regardless of severity. The annualised event rate represents the average number of events per patient during a 1-year period.

Time frame: Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

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

Overview

Conditions

Interventions

Eligibility

Locations (569)

Outcomes

Primary Outcomes

Secondary Outcomes