E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
We want to study patients with indication for antithrombotic drugs who suffers from spontaneous intracerebral hemorrhage (ICH). It has long been unclear whether survivors of ICH should start antithrombotic drugs for continued secondary prevention of vaso-occlusive disease or avoid antithrombotic drugs in case it increases the risk of intracerebral hemorrhage. |
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E.1.1.1 | Medical condition in easily understood language |
We will study the effect of antithrombotic drugs on the risk of a new brain hemorrhage in patients with high risk for thrombosis and previous brain hemorrhage. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
The primary objective is to estimate the relative and absolute effects of antithrombotic drugs on the risk of recurrent symptomatic ICH associated with a policy of starting antithrombotic drugs after the acute phase of spontaneous ICH. |
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E.2.2 | Secondary objectives of the trial |
Secondarily, we aim to determine whether there is an interaction between the presence of brain microbleeds on MRI and the effect of antithrombotic drugs on the risk of recurrent ICH. The trial will show whether ICH recurrence is more common among those with more microbleeds, and the extent to wich this is so. |
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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 |
We will perform a brain MRI - study to test for an interaction between the presence of brain microbleeds and the effects of antithrombotic drugs and explore whether there is a trend in the risk of recurrent ICH with increasing numbers of microbleeds. |
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E.3 | Principal inclusion criteria |
•Patient age ≥18 years. •Spontaneous, primary ICH, of ≥1 day,, i.e.: oNo preceding traumatic brain injury, based on history from the patient/witness of spontaneous symptom onset, and brain imaging appearances consistent of spontaneous ICH (i.e. any brain/bone/soft tissue appearances of trauma must have occurred secondary to a spontaneous ICH) oNo ‘secondary’ or underlying structural cause (e.g. haemorrhagic transformation of an ischaemic stroke, aneurysm, tumour, arteriovenous malformation, or intracerebral venous thrombosis) •Patient have indication for antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of ischaemic events, either antiplatelet drugs (for patients with vascular disease), or anticoagulant drug for patients with atrial fibrillation. •The investigator is uncertain about whether to give or avoid antithrombotic drugs. •Consent to randomisation from the patient (or personal / legal / professional representative if the patient does not have mental capacity, and waiver of consent is accepted in the patients country). •CT or MRI (for patients in MRI sub-study) is performed before randomisation.
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E.4 | Principal exclusion criteria |
•Clear indication for antiplatelet or anticoagulant treatment (e.g. prosthetic heart valves). •Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception. •For patients in MRI substudy: Contraindication for the brain MRI •Malignancy With life expectancy less than 2 years
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E.5 End points |
E.5.1 | Primary end point(s) |
Fatal or non-fatal symptomatic ICH. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Annually for two years, and after 5 and 10 years . |
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E.5.2 | Secondary end point(s) |
•Functional outcome at two years (according to the modified Rankin Scale) •Death of any cause •Vascular death •Symptomatic epidural, subdural, or subarachnoid haemorrhage •Symptomatic major extracranial haemorrhage •Ischaemic events: transient ischaemic attack, ischaemic stroke, unstable angina, acute myocardial infarction (type 1), peripheral arterial occlusion, mesenteric ischaemia, retinal arterial occlusion, deep vein thrombosis or pulmonary embolism.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Annually for two years, and after 5 and 10 years . |
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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 | 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) | 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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open for patient and treating doctor. Blinded for the investigator. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 51 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
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 | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |