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

Tracking Information
First Submitted Date ICMJE	September 10, 2014
First Posted Date ICMJE	September 12, 2014
Last Update Posted Date	September 3, 2018
Actual Study Start Date ICMJE	November 27, 2014
Actual Primary Completion Date	August 14, 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 10, 2014)	Time to first recurrent stroke (ischemic, hemorrhagic, or unspecified) [ Time Frame: up to 36 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT02239120 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 10, 2014)	Time to Ischemic Stroke [ Time Frame: up to 36 months ]; Composite endpoint of (time to) nonfatal stroke, nonfatal myocardial infarction (MI) and cardiovascular death [ Time Frame: up to 36 months ]; Time to Disabling stroke (modified Rankin Scale greater than or equal to 4, as determined 3 months after recurrent stroke) [ Time Frame: up to 36 months ]; Time to All-cause death [ Time Frame: up to 36 months ]; Time to first major bleed [ Time Frame: up to 36 months ]; Time to first intracranial hemorrhage [ Time Frame: up to 36 months ]; Time to life-threatening bleed [ Time Frame: up to 36 months ]; Fatal bleed [ Time Frame: up to 36 months ]; Time to any bleed (all severities) [ Time Frame: up to 36 months ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source (RE-SPECT ESUS)
Official Title ICMJE	Randomized, Double-blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate (110 mg or 150 mg, Oral b.i.d.) Versus Acetylsalicylic Acid (100 mg Oral q.d.) in Patients With Embolic Stroke of Undetermined Source (RESPECT ESUS)
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 Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
Condition ICMJE	Stroke; Secondary Prevention
Intervention ICMJE	Drug: optional ASA as comedication optional concomitant treatment which can be used for patients with coronary artery disease. It is not required for these pts.; Drug: placebo to ASA placebo to comparator drug; Drug: placebo to optional ASA as comedication optional concomitant treatment which can be used for patients with coronary artery disease. It is not required for these pts.; Drug: placebo to dabigatran etexilate placebo; Drug: ASA 100 mg active comparator drug; Drug: dabigatran etexilate active drug
Study Arms	Experimental: dabigatran etexilate 110 or 150 mg 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.) Interventions: Drug: optional ASA as comedication Drug: placebo to ASA Drug: dabigatran etexilate; Active Comparator: 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 Interventions: Drug: placebo to optional ASA as comedication Drug: placebo to dabigatran etexilate Drug: ASA 100 mg
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 26, 2018)	5390
Original Estimated Enrollment ICMJE; (submitted: September 10, 2014)	6000
Actual Study Completion Date	August 14, 2018
Actual Primary Completion Date	August 14, 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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 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 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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 150 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Croatia, Czechia, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, New Zealand, Peru, Poland, Portugal, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United States
Removed Location Countries	Czech Republic
Administrative Information
NCT Number ICMJE	NCT02239120
Other Study ID Numbers ICMJE	1160.189; 2013-003444-24 ( EudraCT Number )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Boehringer Ingelheim
Study Sponsor ICMJE	Boehringer Ingelheim
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account	Boehringer Ingelheim
Verification Date	August 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP