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

• Register: EUCTR
• Last refreshed on: 1 October 2018
• Main ID: EUCTR2013-003444-24-AT
• Date of registration: 25/09/2014
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim RCV GmbH & Co KG
• Public title: Dabigatran etexilate for Secondary Stroke Prevention in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS)
• Scientific title: 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) - RESPECT ESUS
• Date of first enrolment: 04/11/2014
• Target sample size: 6750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003444-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Croatia, Czech Republic, Estonia, European Union, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, New Zealand, Peru, Poland, Portugal, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Thailand, United States

Contacts

• Name: QRPE PSC CT information Disclosure
• Affiliation: Boehringer Ingelheim RCV GmbH & Co KG

• Name: QRPE PSC CT information Disclosure
• Affiliation: Boehringer Ingelheim RCV GmbH & Co KG

Key inclusion & exclusion criteria

Inclusion criteria:
- Age = 60 years or: Age 18-59 years plus at least one of the following additional risk factors for stroke: a) Mild to moderate heart failure, i.e. NYHA Class = 3 with left ventricular ejection fraction = 40% as documented by e.g. echocardiogram, radionuclide or contrast angiogram in the last 6 months, 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 TIA (before index stroke), f) CHA2DS2-VASc score = 3
- 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 any clear or definite Episode of AF (within a 20 hour period, either as single episode or cumulative time of multiple episodes).

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:
- 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) MI, i) valvular vegetations, or j) infective endocarditis.
- Any indication that requires treatment with an anticoagulant as per Investigator`s judgment.
- History of AF (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 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.
- Lacunar stroke. Lacunar infarcts of restricted size in the deep parts of the brain in the territories of small penetrating arteries. They are absent from the cerebral and cerebellar cortex. On brain CT and MR images they are <1.5 cm in largest Diameter or <2.0 cm if measured on MRI diffusion sequences. In several pathological studies, sites of predilection included the lenticular nucleus, thalamus, central white matter, internal capsule, centrum ovale, corpus callosum, basis pontis, and, rarely, the cerebellum, midbrain and medulla. Infarcts <1.5 cm in largest diameter, or <2.0 cm if measured on MRI diffusion sequences, in the dorsal or lateral areas of the brainstem, in the territory of circumferential, rather than deep penetrating, arteries are not lacunar infarcts (note: history of lacunar stroke is not exclusionary).
22. Any duration of atrial fibrillation
Further exclusion criteria apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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: 20.0 Level: PT Classification code 10067167 Term: Cerebellar embolism System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10014498 Term: Embolic stroke System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10060839 Term: Embolic cerebral infarction System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10074422 Term: Brain stem embolism System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Pradaxa
Product Name: dabigatran etexilate 110 mg
Product Code: BIBR 1048 MS
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: dabigatran etexilate
Current Sponsor code: BIBR 1048 MS
Other descriptive name: DABIGATRAN ETEXILATE MESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 110-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Pradaxa
Product Name: dabigatran etexilate 150 mg
Product Code: BIBR 1048 MS
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: dabigatran etexilate
Current Sponsor code: BIBR 1048 MS
Other descriptive name: DABIGATRAN ETEXILATE MESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: ASS 100 mg
Product Name: ASS 100 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: acetylsalicylic acid
Other descriptive name: ACETYLSALICYLIC ACID
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100 -
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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)

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.

Timepoint(s) of evaluation of this end point: up to 36 months

Secondary Outcome(s)

Secondary end point(s): 1: Time to first major bleed

2: Time to Ischemic Stroke

3: Composite endpoint of (time to) nonfatal stroke, nonfatal myocardial infarction (MI) and cardiovascular death

4: Time to Disabling stroke (modified Rankin Scale greater than or equal to 4, as determined 3 months after recurrent stroke)

5: Time to All-cause death

6: Time to first intracranial hemorrhage

7: Time to life-threatening bleed

8: Fatal bleed

9: Time to any bleed (all severities)

Timepoint(s) of evaluation of this end point: 1: up to 36 months
2: up to 36 months
3: up to 36 months
4: up to 36 months
5: up to 36 months
6: up to 36 months
7: up to 36 months
8: up to 36 months
9: up to 36 months

Secondary ID(s)

2013-003444-24-PT

1160.189

NCT02239120

Source(s) of Monetary Support

Boehringer Ingelheim RCV GmbH & Co KG