E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cerebral venous thrombosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008138 |
E.1.2 | Term | Cerebral venous thrombosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the TO-ACT trial is to determine if endovascular thrombolysis improves the functional outcome at 12 months of patients with a severe form of cerebral venous thrombosis. |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints
1. Favorable outcome (mRS 0 or 1) at 6 months
2. Rate of death or dependency at 6 and 12 months (mRS 3-6)
3. Outcome on the mRS across the ordinal continuum at 6 and 12 months
4. Recanalisation at 6 months using MR-venography or CT venography
Safety endpoints
1. Safety of endovascular thrombolysis as defined by major extracranial hemorrhagic com-plications and symptomatic intracranial hemorrhagic complications within one week fol-lowing the intervention.
2. Mortality at 6 months
3. All serious adverse events
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. CVT, confirmed by cerebral angiography (with intra-arte¬rial contrast injection), magnetic resonance venography or computed tomograhy venography.
2. Severe form of CVT with a relatively high chance of poor outcome, as determined by the presence of one of the following disease characteristics: mental status disorder, coma, intracerebral hemorrhage or thrombosis of the deep cerebral venous system.
3. Uncertainty by the treating physician if ET or standard heparin therapy is the optimal therapy for the patient.
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E.4 | Principal exclusion criteria |
• Age less than 18 years
• Duration from diagnosis to randomization of more than 10 days
• Recurrent CVT
• Any thrombolytic therapy within last 7 days
• Pregnancy (women in the puerperium may be included)
• Isolated cavernous sinus thrombosis
• Isolated intracranial hypertension (without focal neurological signs, with the exception of papilloedema and 6th cranial nerve palsy)
• Contraindication for anti-coagulant or thrombolytic treatment
documented generalized bleeding disorder
concurrent thrombocytopenia (<100 x 10E9/L)
documented severe hepatic or renal dysfunction, that interferes with normal coagulation
uncontrolled severe hypertension (diastolic > 120 mm Hg)
known recent (< 3 months) gastrointestinal tract hemorrhage (not including hemorrhage from rectal hemorrhoids)
• Any known associated condition (such as terminal cancer) with a poor short term (1 year) prognosis independent of CVT
• Clinical and radiological signs of impending transtentorial herniation due to large space-occupying lesions (e.g. large cerebral venous infarcts or hemorrhages)
• Recent (< 2 weeks) major surgical procedure (does not include lumbar puncture) or severe cranial trauma
• Known allergy against contrast fluid used during endovascular procedures or the throm-bolytic drug used in that particular centre
• Previously legally incompetent prior to CVT
• No informed consent
General notes on exclusion criteria:
1. Intracerebral hemorrhage, hemorrhagic infarction, or subarachnoid hemorrhage as a result of CVT is not an exclusion criterion for this study.
2. Initial treatment with heparin is not an exclusion criterion for this study. Patients who deteriorate while on heparin treatment may be included and randomized if they fulfill the criteria.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint
Outcome on the modified Rankin Scale (mortality included) at 12 months after randomization is considered as the primary study outcome to determine the efficacy of thrombolytic treatment. |
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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 | No |
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 | Yes |
E.8.1.3 | Single blind | No |
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 | No |
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 |
Standard treatment (i.e. heparin therapy) |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | Information not present in EudraCT |
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 |
Brazil |
France |
Netherlands |
Portugal |
United Kingdom |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 2 |