E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
Prävention eines erneuten Schlaganfalls bei Patienten mit embolischem Schlaganfall unbestimmter Ursache (RESPECT ESUS) |
|
E.1.1.1 | Medical condition in easily understood language |
prevention of secondary stroke in pts with recent history of ESUS |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067167 |
E.1.2 | Term | Cerebellar embolism |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014498 |
E.1.2 | Term | Embolic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060839 |
E.1.2 | Term | Embolic cerebral infarction |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10074422 |
E.1.2 | Term | Brain stem embolism |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
The trial will also characterize the safety of dabigatran etexilate in this
setting. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Assay Validation and Biomarker
Protocol Date: 27-JUN-14
Protocol Version: final |
|
E.3 | Principal 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 duration5
(within a 20 hour period, either as single episode or cumulative time of
multiple episodes).
Further inclusion criteria apply. |
|
E.4 | Principal 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.
Further exclusion criteria apply. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to first recurrent stroke (ischemic, hemorrhagic, or unspecified) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | 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) |
|
E.5.2.1 | 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 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 70 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 169 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
China |
Colombia |
Croatia |
Czech Republic |
European Union |
France |
Germany |
Hong Kong |
Hungary |
India |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Peru |
Poland |
Portugal |
Russian Federation |
Serbia |
Singapore |
Slovakia |
Slovenia |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |