E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cerebral vein and dural sinus thrombosis |
trombosis de seno dural y venosa cerebral |
|
E.1.1.1 | Medical condition in easily understood language |
patients with a blood clot in the venous system of the brain |
pacientes con un coágulo en el sistema venoso del cerebro |
|
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 | HLT |
E.1.2 | Classification code | 10008209 |
E.1.2 | Term | Cerebrovascular venous and sinus thrombosis |
E.1.2 | System Organ Class | 100000004852 |
|
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 |
to compare net clinical benefit of the treatment arms, as measured by the composite of venous thrombotic events (VTE) (recurring CVT, deep venous thrombosis (DVT) of any limb, pulmonary embolism (PE), or splanchnic vein thrombosis) + major bleeding according to ISTH criteria |
Comparar el beneficio clínico neto de los brazos de tratamiento, medido por el criterio de valoración compuesto: eventos tromboembólicos venosos (TEV) (CVT recurrente; trombosis venosa profunda (TVP) de cualquier extremidad, embolismo pulmonar (EP), trombosis venosa esplácnica) + hemorragia mayor de acuerdo a los criterios de la ISTH |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives include a comparison of additional efficacy and safety parameters |
Los objetivos secundarios incluyen una comparación de parámetros adicionales de eficacia y seguridad. |
|
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 |
Development of dural fistuals Protocol Date: 07-JUL-16 Protocol Version: 1.0 |
Desarrollo de fístulas durales Fecha protocolo: 07-JUL-16 Versión protocolo: 1.0 |
|
E.3 | Principal inclusion criteria |
- Written informed consent in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and local legislation and/or regulations - Confirmed diagnosis of Cerebral Venous or dural sinus thrombosis (CVT), with or without intracranial haemorrhage - Completion of anticoagulation therapy for 5-15 days which has been administered until randomisation; anticoagulation must include full-dose low molecular weigth heparin or unfractionated heparin - Eligibility for treatment with an oral anticoagulant Further inclusion criteria apply |
- Consentimiento informado por escrito de acuerdo con las guías ICH en BPC y con la legislación/regulaciones locales - Diagnóstico confirmado de trombosis de seno dural y venosa cerebral (CVT), con o sin hemorragia intracraneal - Finalización de tratamiento anticoagulante durante 5-15 días, que se ha administrado hasta la aleatorización; la anticoagulación debe incluir dosis completas de heparina de bajo peso molecular o heparina no fraccionada - Elegibilidad para el tratamiento con un anticoagulante oral Se aplican criterios de inclusión adicionales. |
|
E.4 | Principal exclusion criteria |
- CVT associated with central nervous system infection or due to head trauma - Planned surgical treatment for CVT - Conditions associated with increased risk of bleeding - History of symptomatic non-traumatic intracranial haemorrhage with risk of recurrence according to Investigator judgment - Treatment with an antithrombotic regimen before CVT diagnosis and requiring continuation of that treatment for the original diagnosis without change in the regimen - Severe renal impairment - Active liver disease - Preganancy, nursing or planning to become pregnant while in the trial Further exclusion criteria apply |
- CVT asociada con una infección del sistema nervioso central o debido a trauma craneal - Tratamiento quirúrgico planeado para CVT - Condiciones asociadas con un riesgo de sangrado aumentado - Historia de hemorragia intracraneal no-traumática y sintomática con riesgo de recurrencia de acuerdo con el criterio del investigador - Tratamiento con un régimen antitrombótico antes del diagnóstico de CVT y que requiera continuación de dicho tratamiento para el diagnóstico original sin cambio en el régimen - Insuficiencia renal grave - Enfermedad hepática activa - Embarazo, lactancia o previsión de quedarse embarazada durante el ensayo Se aplican criterios de exclusión adicionales. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1: Composite of the number of patients with major bleeding according to ISTH criteria and Venous Thrombotic Event (VTE) (recurring CVT; deep venous thrombosis (DVT) of any limb, pulmonary embolism (PE), splanchnic vein thrombosis) after up to 24 weeks |
1: Criterio de valoración compuesto: número de pacientes con hemorragia mayor de acuerdo a los criterios de la ISTH (International Society on Thrombosis and Haemostasis) y evento tromboembólico venoso (TEV) (CVT recurrente; trombosis venosa profunda (TVP) de cualquier extremidad, embolismo pulmonar (EP), trombosis venosa esplácnica) después de hasta 24 semanas |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: up to 24 weeks |
1: hasta 24 semanas |
|
E.5.2 | Secondary end point(s) |
1: Number of patients with recurring CVT; DVT of any limb, PE or splanchnic vein thrombosis after up to 24 weeks
2: Cerebral venous recanalisation as measured by the change in number of occluded cerebral veins and sinuses after up to 24 weeks
3: Number of patients with major bleeding according to ISTH criteria after up to 24 weeks
4: Composite endpoint of number of patients with new ICH or worsening of the haemorrhagic component of a previous lesion after up to 24 weeks
5: Number of patients with clinically relevant non-major bleeding events (CRNMBE) after up to 24 weeks
6: Number of patients with major bleeding according to ISTH criteria or CRNMBE after up to 24 weeks
7: Number of patients with any bleeding event after up to 24 weeks |
1: Número de pacientes con CVT recurrente; TVP de cualquier extremidad, EP o trombosis venosa esplácnica después de hasta 24 semanas
2: Recanalización venosa cerebral determinada por el cambio en el número de venas y senos cerebrales ocluidos después de hasta 24 semanas
3: Número de pacientes con sangrado mayor según los criterios ISTH después de hasta 24 semanas
4:Criterio de valoración compuesto del número de pacientes con nuevo ICH o empeoramiento de componente hemorrágico de una lesión previa después de hasta 24 semanas
5: Número de pacientes con eventos hemorrágicos no mayores clínicamente relevantes (HNMCR) después de hasta 24 semanas
6: Número de pacientes con sangrado mayor según los criterios ISTH o EHNGCR después de hasta 24 semanas
7:Número de pacientes con cualquier episodio de sangrado después de hasta 24 semanas |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: up to 24 weeks
2: up to 24 weeks
3: up to 24 weeks
4: up to 24 weeks
5: up to 24 weeks
6: up to 24 weeks
7: up to 24 weeks |
1: hasta 24 semanas
2: hasta 24 semanas
3: hasta 24 semanas
4: hasta 24 semanas
5: hasta 24 semanas |
|
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 | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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 |
Belgium |
Canada |
France |
Germany |
India |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Russian Federation |
Spain |
|
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 4 |