E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary prevention of venous thromboembolism |
Prevención secundaria de la tromboembolia venosa |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of blood clots in the veins |
Prevención de la formación de coágulos sanguíneos en las venas |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 100000004865 |
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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 |
To assess the safety of dabigatran etexilate used for secondary prevention of venous thromboembolism in children from 0 to less than 18 years of age. |
Evaluar la seguridad de dabigatrán etexilato utilizado para la prevención secundaria de la tromboembolia venosa en niños de 0 a menos de 18 años de edad. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female subjects 0 to less than 18 years of age at the time of informed consent / assent - Previously documented objective diagnosis of VTE, followed by completed course of initial VTE treatment (for at least 3 months) or completed study treatment (i.e. reached Visit 8) in the 1160.106 trial - Presence of an unresolved clinical risk factor requiring further anticoagulation for secondary VTE prevention (e.g. central venous line, underlying disease, thrombophilia, etc.) - Written informed consent form (ICF) provided by the patient's parent or legal guardian and assent provided by the patient (if applicable) at the time of ICF signature according to local regulations. |
1.Pacientes de ambos sexos de 0 a menos de 18 años de edad en el momento del consentimiento/asentimiento informado. 2.Diagnóstico objetivo documentado previamente de VTE, seguido de un ciclo completo de tratamiento inicial para la VTE (durante un mínimo de 3 meses) o tratamiento del estudio completado (es decir, haber llegado a la visita 8) en el ensayo 1160.106 3.Presencia de un factor de riesgo clínico no resuelto que requiere tratamiento anticoagulante adicional para la prevención secundaria de la VTE (p. ej., vía venosa central, enfermedad subyacente, trombofilia, etc.). 4.Consentimiento informado por escrito proporcionado por el progenitor o tutor legal del paciente y asentimiento del paciente (si procede) en el momento de la firma del ICF, según la normativa local. |
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E.4 | Principal exclusion criteria |
- Conditions associated with an increased risk of bleeding - Renal dysfunction (eGFR < 80 mL/min/1.73m2 using the Schwartz formula) or requirement for dialysis - Active infective endocarditis - Subjects with a mechanical or a biological heart valve prosthesis - Hepatic disease: Active liver disease, including known hepatitis A, B or C or Persistent alanine aminotransferase (ALT) or aspartate transaminase (AST) or alkaline phosphatase (AP) > 2 × upper limit of normal (ULN) within 3 months of screening - Pregnant or breast feeding females. Females who have reached menarche and are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study and / or do not agree to adhere to pregnancy testing required by this protocol - Anemia (hemoglobin < 80g/L) or thrombocytopenia (platelet count < 80 x 109/L) at screening. Transfusions during the screening period are allowed, provided that a satisfactory hemoglobin or platelet level is attained prior to visit 2 - Patients who have taken restricted medication prior to first dose of study medication - Patients who have received an investigational drug in the past 30 days prior to screening, except patients who have completed the treatment period (up to Visit 8) in 1160.106 trial - Patients who are allergic/sensitive to any component of the study medication including solvent - Patients or parents/legal guardians considered unreliable to participate in the trial per investigator judgment or any condition which would present a safety hazard to the patient based on investigator judgment |
1.Patologías asociadas a un riesgo alto de hemorragia: 2.Insuficiencia renal (eGFR < 80 ml/min/1,73 m2 usando la fórmula de Schwartz) o necesidad de diálisis. 3.Endocarditis infecciosa activa 4.Pacientes con una prótesis valvular cardíaca mecánica o biológica. 5.Enfermedad hepática: a.Enfermedad hepática activa, incluida hepatitis A, B o C diagnosticada o, b.Niveles persistentes de alanina-aminotransferasa (ALT), aspartato-transaminasa (AST) o fosfatasa alcalina (AP) > 2 veces el límite superior de la normalidad (ULN) dentro de los 3 meses de la selección. 6.Mujeres embarazadas o en periodo de lactancia. Mujeres que hayan llegado a la menarquia y no utilicen un método anticonceptivo aceptable o no tienen intención de continuar utilizando este método durante todo el estudio y no acceden a someterse a la prueba de embarazo exigida en este protocolo. 7.Anemia (hemoglobina < 80 g/l) o trombocitopenia (cifra de plaquetas < 80 x 109/l) en la selección. Las transfusiones están permitidas durante el periodo de selección, pero sólo si se ha alcanzado un nivel de hemoglobina o plaquetas satisfactorio antes de la visita 2. 8.Pacientes que hayan recibido medicación prohibida antes de la primera dosis de la medicación del estudio. 9.Pacientes que hayan recibido un fármaco en investigación en los 30 días previos a la selección, excepto los pacientes que hayan completado el periodo de tratamiento (hasta la visita 8) en el estudio 1160.106. 10.Pacientes alérgicos/sensibles a cualquiera de los componentes de la medicación del estudio, incluido el disolvente. 11.Pacientes o padres/tutores legales a los que el investigador no considere aptos para participar en el estudio, o cualquier enfermedad que pudiera poner en peligro la seguridad del paciente, según el criterio del investigador. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: Recurrence of venous thromboembolism (VTE)
2: Major and minor (including clinically relevant non-major (CRNM)) bleeding events
3: Mortality overall and related to thrombotic or thromboembolic events |
1: Recurrencia de la tromboembolia venosa (VTE) 2: Acontecimientos hemorrágicos graves y leves, incluida la hemorragia no grave clínicamente relevante (CRNM) 3: Mortalidad global y relacionada con acontecimientos trombóticos o tromboembólicos |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: 6 and 12 months
2: 6 and 12 months
3: 6 and 12 months |
1: 6 y 12 meses
2: 6 y 12 meses
3: 6 y 12 meses |
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E.5.2 | Secondary end point(s) |
1: Occurrence of post-thrombotic syndrome (PTS)
2: Central measurement of aPTT (Activated partial thromboplastin time)
3: Central measurement of ECT (Ecarin clotting time )
4: Number of dabigatran etexilate dose adjustments during treatment period |
1: Aparición de síndrome postrombótico (PTS) 2: Determinación central de aPTT (tiempo parcial de tromboplastina activada) 3: Determinación central de ECT (tiempo de coagulación de Ecarin) 4: Número de ajustes de dosis de dabigatrán etexilato durante el periodo de tratamiento |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 6 and 12 months
2: after 3 weeks of treatment
3: after 3 weeks of treatment
4: 12 months |
1: 6 y 12 meses
2: después de 3 semanas de tratamiento
3: después de 3 semanas de tratamiento
4: 12 meses |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Colombia |
Czech Republic |
Finland |
France |
Germany |
Greece |
Israel |
Italy |
Lithuania |
Mexico |
Norway |
Russian Federation |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
Ukraine |
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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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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 | 9 |
E.8.9.1 | In the Member State concerned days | 26 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 26 |