E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Eligible paediatric patients from trial 1160.106 or 1160.108 treated with dabigatran etexilate who require emergency surgery/urgent procedures requiring rapid reversal of the anticoagulant effect of dabigatran prior to these emergency surgery/urgent procedures or patients who exhibiting signs and symptoms of life-threatening or uncontrolled bleeding requiring urgent medical intervention, could participate |
Son elegibles los pacientes pediátricos de los ensayos 1160.106 y 1160.108, tratados con dabigatrán etexilato que necesitan anulación rápida del efecto anticoagulante de dabigatrán antes de la cirugía de emergencia/procedimientos urgentes o pacientes que presenten signos y síntomas de hemorragias potencialmente mortales o no controladas que hagan necesaria una intervención médica de urgencia. |
|
E.1.1.1 | Medical condition in easily understood language |
Serious bleeding/emergency surgery or urgent procedure after treatment with dabigatran |
Cirugía de emergencia/procedimientos de urgencia o pacientes con hemorragias tras tratamiento con dabigatrán. |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066899 |
E.1.2 | Term | Venous thromboembolism |
E.1.2 | System Organ Class | 100000023031 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 100000022822 |
|
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 demonstrate the safety of idarucizumab, as assessed by the occurrence of patients with drug related adverse events (including immune reactions) and all-cause mortality in paediatric venous thromboembolism (VTE) patients treated with dabigatran in ongoing clinical trials who require emergency surgery/urgent procedures or patients who have life-threatening or uncontrolled bleeding which requires urgent intervention, when rapid reversal of the anticoagulant effects of dabigatran is needed. |
Demostrar la seguridad de idarucizumab, evaluada mediante la detección de pacientes con acontecimientos adversos relacionados con el fármaco (incluyendo reacciones inmunitarias) y mortalidad por cualquier causa en pacientes pediátricos con tromboembolismo venoso (TEV) tratados con dabigatrán en ensayos clínicos en curso que necesitan cirugía de emergencia/procedimientos de urgencia o pacientes con hemorragias potencialmente mortales o no controladas que hacen necesaria una intervención urgente, en la que es necesario anular rápidamente los efectos anticoagulantes de dabigatrán. |
|
E.2.2 | Secondary objectives of the trial |
Assessments of the reversal of dabigatran, bleeding status or emergency surgery/urgent procedures, clinical outcomes, pharmacokinetics of dabigatran and idarucizumab. |
Evaluación de la reversión de dabigatran, estado de la hemorragia, cirugía de emergencia/procedimientos de urgencia, resultados clínicos y farmacocinéticos de dabigatrán e idarucizumab. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients taking dabigatran etexilate in the paediatric trials 1160.106 or 1160.108 are eligible for this trial if they meet the following criteria:
Group A:
- Overt bleeding judged by the treating physician to require a reversal agent.
- Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
- Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
- Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
- Written informed consent provided by the patient (and/or the patient¿s legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with GCP and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible.
Group B:
- A condition requiring an emergency surgery or invasive procedure where adequate haemostasis is required. Emergency is defined as need for surgery or intervention within the following 8 hours.
- Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
- Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
- Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
- Written informed consent provided by the patient (and/or the patient¿s legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with GCP and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible. |
Pacientes en tratamiento con dabigatrán etexilato en ensayos pediátricos 1160.106 o 1160.108 son escogidos para este ensayo si cumplen los siguientes criterios:
Grupo A:
-Sangrado sintomático, a juicio del médico que requiera un agente de reversión
-Actualmente en tratamiento con dabigatran etexilato en el contexto de un ensayo clinico con dabigatran etexilato (1160.106 o 1160.108).
-Niños/as y adolescentes de 0 a menos de 18 años en el momento del consentimiento informado/asentimiento de la participación en los ensayos 1160.106 o 1160.108.
-Mujeres con maternidad potencial (en edad fertil, después del primer ciclo menstrual) deben utilizar métodos anticonceptivos de acuerdo a los requisitos los ensayos 1161.106 u 1160.108 en el que estén participando.
-Consentimiento informado proporcionado al paciente (y/o a su representante legal), y hoja de asentimiento proporcionada al paciente (en caso necesario) firmado y fechado de acuerdo a GCP y legislación local antes de la admisión al ensayo. Si el paciente no puede proporcionar su consentimiento en el momento de la emergencia, se tendrá que obtener tan pronto como sea posible.
Grupo B:
-Una condición que requiera una cirugía de emergencia o un procedimiento invasivo cuando se necesite hemostasia adecuada.
- Actualmente en tratamiento con dabigatran etexilato en el contexto de un ensayo clinico con dabigatran etexilato (1160.106 o 1160.108).
-Niños/as y adolescentes de 0 a menos de 18 años en el momento del consentimiento informado/asentimiento de la participación en los ensayos 1160.106 o 1160.108.
-Mujeres con maternidad potencial (en edad fertil, después del primer ciclo menstrual) deben utilizar métodos anticonceptivos de acuerdo a los requisitos los ensayos 1161.106 u 1160.108 en el que estén participando.
-Consentimiento informado proporcionado al paciente (y/o a su representante legal), y hoja de asentimiento proporcionada al paciente (en caso necesario) firmado y fechado de acuerdo a GCP y legislación local antes de la admisión al ensayo. Si el paciente no puede proporcionar su consentimiento en el momento de la emergencia, se tendrá que obtener tan pronto como sea posible. |
|
E.4 | Principal exclusion criteria |
Group A:
- Patients with minor bleeding (e.g. epistaxis, haematuria) who can be managed with standard supportive care.
- Patients with no clinical signs of bleeding.
- Patients with body weight < 2.5 kg
- Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol or infants with unknown hereditary fructose intolerance status.
- Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.
Group B:
- A surgery or procedure which is elective or where the risk of uncontrolled or unmanageable bleeding is low.
- Patients with body weight < 2.5 kg
- Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol or infants with unknown hereditary fructose intolerance status.
- Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial. |
Grupo A:
-Pacientes con hemorragia leve (p.ej: epistasia, hematuria) que pueden ser tratados con tratamiento estándar de apoyo.
-Pacientes sin signos clínicos de sangrado.
-Pacientes con peso < 2.5 kg.
-Contraindicaciones a la medicación del ensayo, incluyendo hipersensibilidad al fármaco o sus excipientes; p.ej: pacientes con intolerancia a la fructosa hereditaria que puedan reaccionar al sorbitol o bebés con estado desconocido de intolerancia a la fructosa hereditaria.
-Mujeres embarazadas, en período de lactancia o que tienen pensado quedarse embarazadas durante el ensayo.
Grupo B:
-Una cirugía o procedimiento opcional o cuyo riesgo de hemorragia no controlada es bajo.
- Pacientes con peso < 2.5 kg.
-Contraindicaciones a la medicación del ensayo, incluyendo hipersensibilidad al fármaco o sus excipientes; p.ej: pacientes con intolerancia a la fructosa hereditaria que puedan reaccionar al sorbitol o bebés con estado desconocido de intolerancia a la fructosa hereditaria.
-Mujeres embarazadas, en período de lactancia o que tienen pensado quedarse embarazadas durante el ensayo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1: Safety of idarucizumab in a paediatric population as assessed by the occurrence of drug-related adverse events (including immune reactions) and all-cause mortality during the trial. |
1: Seguridad de idarucizumab en la población pediátrica evaluada como la ocurrencia de reacciones adversas relacionadas con el fármaco (incluyendo reacciones inmunológicas) y mortalidad de cualquier causa durante el ensayo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: 30 days post-dose |
1: 30 días tras el tratamiento |
|
E.5.2 | Secondary end point(s) |
1: Percent change of coagulation tests (dTT, ECT) at 30 minutes post-dose compared to pre-dose.
2: Time to achieve complete reversal of dabigatran effect, based on coagulation tests (dTT and ECT).
3: Duration of complete reversal of dabigatran effect sustained at 24 hours post-dose, based on coagulation tests (dTT and ECT).
4: Cessation of bleeding (Group A patients only).
5: Bleeding status and other clinical conditions that may contribute to bleeding (Group A patients only) during the trial.
6: Development of treatment-emergent ADA with cross reactivity to idarucizumab at
30 days post-dose of idarucizumab (binary). |
1: Cambio porcentual de las pruebas de coagulación (dTT, ECT) a los 30 minutos tras el tratamiento en comparación con antes del tratamiento.
2: Tiempo de alcance del efecto de reversión de dabigatrán, basado en tests de coagulación (dTT y ECT).
3: Duración de la reversión completa del efecto de dabigatrán mantenida a las 24 h tras el tratamiento, basado en test de coagulación (dTT y ECT).
4: Cese de hemorragia (solo en pacientes del grupo A).
5: Hemorragia u otras condiciones clínicas que puedan contribuir a la hemorragia (solo en pacientes del grupo A) durante el ensayo.
6: Desarrollo de ADA emergente de tratamiento con reactividad cruzada con idarucizumab a los 30 días post-dosis de idarucizumab (binario). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 30 minutes post-dose
2: Up to 24 hours post-dose
3: Up to 24 hours post-dose
4: Up to 24 hours post-dose
5: 30 days post-dose
6: 30 days post-dose |
1: 30 minutos tras el tratamiento
2: Hasta 24 horas tras el tratamiento
3: Hasta 24 horas tras el tratamiento
4: Hasta 24 horas tras el tratamiento
5: 30 días tras el tratamiento
6: 30 días tras el tratamiento |
|
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 | 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 | 60 |
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 |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Lithuania |
Mexico |
Norway |
Poland |
Russian Federation |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
|
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
|
LVLS |
Ultima visita del último paciente |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 23 |