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

Phase 1

Conditions: MedDRA version: 18.1 Level: PT Classification code 10060839 Term: Embolic cerebral infarction System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 18.1 Level: PT Classification code 10014498 Term: Embolic stroke System Organ Class: 10029205 - Nervous system disorders
A study to compare dabigatran etexilate to acetylsalicylic acid in preventing recurrent stroke for patients that already had a stroke caused by an embolus (clot). Despite testing, it is unknown where in the body the embolus developed.
MedDRA version: 18.1 Level: PT Classification code 10067167 Term: Cerebellar embolism System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 18.1 Level: PT Classification code 10074422 Term: Brain stem embolism System Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2013-003444-24-PT

Lead Sponsor: nilfarma - União Internacional de Lab. Farmacêuticos, Lda.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 5830

Inclusion Criteria

1) Age greater than or equal to 60 years
or:
Age 18 to 59 years plus at least one of the following additional risk factors for stroke:
a) Mild to moderate heart failure, i.e. New York Heart Association (NYHA) Class <= 3 with left ventricular ejection fraction b) Diabetes mellitus (either type 1 or type 2)
c) Hypertension requiring medical treatment with antihypertensive medication
d) Patent foramen ovale with no interventional occlusion planned
e) Prior stroke or Transient Ischemic Attach (TIA) (before index stroke)
f) CHA2DS2-VASc (Congestive heart failure, Hypertension, Age >=75, Diabetes, prior Stroke/Transient Ischemic Attack) score >= 3

2) 2a) Ischemic stroke with a brain lesion visualized by neuroimaging (eIther brain CT or 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.
2b) The index stroke must have occurred either:
a. up to 3 months before randomization (Modified Rankin Scale (mRS) <=3 at randomization)
OR
b. 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 (see stroke risk factors a - f as outlined in Inclusion 1).
3) 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 .
4) As evidenced by cardiac monitoring for >= 20 hours with automated rhythm detection, there is absence of atrial fibrillation (AF) > 6 minutes in duration (within a 20 hour period, either as single episode or cumulative time of multiple episodes).
5) The patient must give informed consent in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and local legislation and/or regulations.
Further inclusion criteria apply.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3600

Exclusion Criteria

1. Modified Rankin Scale of >=4 at time of rand. or inability to swallow medications.
2. 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) MI,
i.valvular vegetations, or
j.infective endocarditis.
3. Any indication that requires treatment with an anticoagulant as per Investigator`s judgment.
4. History of AF (unless it was due to reversible causes and has been permanently resolved).
5.Other specific stroke etiology (i.e. cerebral arteritis or arterial dissection, migraine with aura/vasospasm, drug abuse).
6. Primary intracerebral hemorrhage on qualifying neuroimaging
7. Conditions associated with increased risk of bleeding such as:
a) Major surgery in the previous month (in which case the patient may be eligible when one month has passed)
b) Planned major surgery or intervention in the next 3 months
c) History of intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding unless the causative factor has been permanently eliminated or repaired per Investigator judgment (e.g. by surgery)
d) Gastrointestinal hemorrhage within the past six months unless the cause has been permanently eliminated or repaired per Investigator judgment (e.g. by surgery), or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
e) Hemorrhagic disorder or bleeding diathesis, e.g. history of thrombocytopenia or platelet count <100x10^3/uL at screening, von Willebrand disease, hemophilia A or B or other hereditary bleeding disorder, history of prolonged bleeding after surgery/intervention.
f) Fibrinolytic agents within 48 hours of study entry
g) Uncontrolled hypertension Systolic Blood Pressure (SBP) >180mmHg and/or Diastolic Blood Pressure (DBP) >100 mmHg)
h) Any history of intracranial aneurysm (unless it was permanently resolved with either clipping or coiling at least one year prior to the study entry)
8. History of symptomatic nontraumatic intracranial hemorrhage with risk of recurrence according to Investigator judgment
9. Renal impairment with estimated CrCl (as calculated by Cockcroft-Gault equation) <30mL/min at screening, or where Investigator expects CrCl is likely to drop below 30mL/min during the course of the study.
10. History of hypersensitivity or known contraindication to dabigatran etexilate (DE) or ASA.
Further exclusion criteria apply

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of dabigatran etexilate (110 mg b.i.d. or 150 mg b.i.d., with dosing according to age and renal function), to ASA (100 mg once daily) for the prevention of stroke recurrence in patients with embolic stroke of undetermined source.;Secondary Objective: The trial will also characterize the safety of dabigatran etexilate in this setting.;Primary end point(s): Time to first recurrent stroke (ischemic, hemorrhagic, or unspecified);Timepoint(s) of evaluation of this end point: up to 36 months

Secondary Outcome Measures

Name	Time	Method

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