Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source (RE-SPECT ESUS)
- Conditions
- Secondary PreventionStroke
- Interventions
- Drug: placebo to optional ASA as comedication
- Registration Number
- NCT02239120
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5390
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ASA 100 mg ASA 100 mg 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 dabigatran etexilate 110 or 150 mg optional ASA as comedication 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.) dabigatran etexilate 110 or 150 mg placebo to ASA 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.) ASA 100 mg placebo to optional ASA as comedication 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 ASA 100 mg placebo to dabigatran etexilate 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 dabigatran etexilate 110 or 150 mg dabigatran etexilate 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.)
- Primary Outcome Measures
Name Time Method Adjudicated Recurrent Stroke From randomisation until full follow up period, approximately 43 months. 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.
First Major Bleed (Adjudicated) Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months. 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.
- Secondary Outcome Measures
Name Time Method Adjudicated Intracranial Hemorrhage Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months. 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.All-cause Death From randomisation until full follow up period, up to 43 months All-cause death is presented. The annualised event rate represents the average number of events per patient during a 1-year period.
Adjudicated Composite of Non-fatal Stroke, Non-fatal Myocardial Infarction, or Cardiovascular Death From randomisation until full follow up period, up to 43 months 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.
Adjudicated Ischaemic Stroke From randomisation until full follow up period, up to 43 months 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.
Disabling Stroke From randomisation until full follow up period, up to 43 months 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.
Adjudicated Fatal Bleed Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months. 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.
Adjudicated Life-threatening Bleed Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months. 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.Any Bleed (Investigator-reported) Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months. 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.
Trial Locations
- Locations (562)
Bronislava Shafran, MD PC
🇺🇸Phoenix, Arizona, United States
Westside Medical Associates of Los Angeles
🇺🇸Beverly Hills, California, United States
TriWest Research Associates, LLC
🇺🇸El Cajon, California, United States
University of California
🇺🇸San Francisco, California, United States
Glendale Adventist Medical Center
🇺🇸Glendale, California, United States
Collaborative Neuroscience Network, LLC (CNS)
🇺🇸Long Beach, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Huntington Hospital
🇺🇸Pasadena, California, United States
University of Colorado Denver
🇺🇸Fort Collins, Colorado, United States
Scroll for more (552 remaining)Bronislava Shafran, MD PC🇺🇸Phoenix, Arizona, United States