E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study compares different strategies for secondary stroke (or retinal ischaemia) prevention in patients with patent foramen ovale.
The three treatment arms comprise:
1. Endovascular patent foramen ovale closure followed by long-term antiplatelet therapy
2. long-term anticoagulant therapy
3. long-term antiplatelet therapy |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with a small hole in the wall dividing left and right side of the heart: strategies for preventing a second stroke (closure of the hole, 2 types of blood thinning medication) |
|
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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036654 |
E.1.2 | Term | Prevention |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016982 |
E.1.2 | Term | Foramen ovale patent |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042244 |
E.1.2 | Term | Stroke |
E.1.2 | System Organ Class | 100000004852 |
|
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 endovascular PFO closure or anticoagulant therapy versus antiplatelet therapy for secondary stroke prevention, in patients between the ages of 18 and 60 years with PFO with large shunt or PFO associated with atrial septum defect with a history of otherwise unexplained stroke or retinal ischaemia. In the case of superiority of both PFO closure and anticoagulant therapy over antiplatelet therapy, the non-inferiority of endovascular closure of PFO versus anticoagulant therapy will be tested. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety of the treatment options in terms of severe complications
related to drugs, the procedure or the device itself, in order to evaluate the benefit-risk
profile of each treatment option
2. To evaluate the technical success rate of the procedure, defined by: deployment of the
device in the appropriate place and removal of the placement system, successful
implantation with no complications before the patient´s discharge, success of the
procedure with no residual shunt or minimal residual shunt on echocardiography
performed 6 months after the procedure |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- age between 18 and 60 years
- stroke or retinal ischaemia (initial or recurrent) within last 6 months confirmed by
cerebral imaging regardless of the duration of symptoms
- Modified Rankin score 3 or lower
- absence of another identifiable cause of stroke or retinal ischaemia on a thorough
aetiological work-up
- PFO with a large shunt (induced or spontaneous shunt > 30 microbubbles, on TTE
or on TOE) or PFO associated with atrial septal aneurysm on TOE (base of aneurysm
at least 15 mm and excursion > 10 mm)
- the patient must be able to give his written consent |
|
E.4 | Principal exclusion criteria |
- another cause for stroke associated with PFO
- isolated atrial septum defect or ASD associated with PFO but with a haemodynamically
significant left-to-right shunt requiring closure
- previous surgical or endovascular treatment of PFO or ASA
- known or suspected pregnancy (beta-hCG assay must be performed before inclusion)
- breastfeeding
- follow-up impossible or expected poor compliance
- presence of other medical problems that would either lead to inability to complete the
study or interfere with the assessment of outcomes
- participation in another study
- patient unable to understand the informed consent form
- contraindication to the drug treatments or endovascular procedure of the study |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- at 2 months, 6 months and every 6 months thereafter
- end of study visit (within 30 days from the end of the study)
- unscheduled visits in case of stroke recurrence |
|
E.5.2 | Secondary end point(s) |
- disabling stroke
- ischaemic stroke
- cerebral haemorrhage
- TIA
- systemic embolism
- ischaemic stroke, TIA or systemic embolism
- all-cause mortality
- vascular death
- related to the device implanted:
- procedure- or device-related complications
- success of device implantation, defined by deployment of the
device in the appropriate place and removal of the placement
system
- success of the procedure, defined as successful implantation
with no complications before the patient´s discharge
- success of PFO closure, defined by success of the procedure
with no residual shunt or minimal residual shunt on echocardio-
graphy performed 6 months after the procedure
- relationship between presence of a residual shunt and stroke
recurrence
- moderate or severe bleeding, including fatal haemorrhages and
intracranial haemorrhages |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
(analogous to E.5.1.1)
- at 2 months, 6 months and every 6 months thereafter
- end of study visit (within 30 days from the end of the study)
- unscheduled visits in case of stroke recurrence
for secondary end points related to the device implanted
compare the definitions above (E.5.2) |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
blinded evaluation of outcomes |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
Endovascular closure of persistent foramen ovale + long term antiplatelet therapy |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
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 | 5 |
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 | 7 |
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 |