E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Traumatic Brain Injury |
Traumatismo craneal |
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E.1.1.1 | Medical condition in easily understood language |
Damage to the brain caused by a sudden external force |
Daño cerebral causado por una fuerza externa repentina |
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E.1.1.2 | Therapeutic area | Diseases [C] - Injuries, poisonings, and occupational diseases [C21] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060690 |
E.1.2 | Term | Traumatic brain injury |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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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 CRASH-3 trial will see if a drug called tranexamic acid will improve outcomes for people who have suffered a traumatic head injury. The main outcome is its effect on death within 28 days of the head injury. We will also assess the cause of death. |
El estudio CRASH-3 va a comprobar si un fármaco denominado ácido tranexámico mejora la evolución de pacientes que han sufrido un traumatismo cerebral. La variable objetivo primaria es la mortalidad a los 28 días. Se valorará también la causa de la muerte. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives will be to assess whether using tranexamic acid leads to better outcomes such as reduced disability, fewer days in intensive care, and fewer surgical interventions. In addition, we will assess whether there is any increase in serious outcomes including heart attack, stroke and blood clots in the legs or lungs, and seizures. |
Los objetivos secundarios incluyen la valoración del efecto del ácido tranexámico en otras variables como reducción de la discapacidad, menor número de días en cuidados intensivos, y un menor número de intervenciones quirúrgicas. Además, vamos a evaluar si hay algún aumento en los resultados graves, incluyendo infarto de miocardio, accidente cerebrovascular y coágulos sanguíneos en las piernas o los pulmones, y convulsiones. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult (16 years and older) with traumatic brain injury (TBI) ? who are within 8 hours of injury ? with any intracranial bleeding on CT scan OR GCS ?12 if no scan available, and ? who have no significant extra cranial bleeding (needing immediate blood transfusion) ? The fundamental eligibility criterion is the responsible clinician?s ?uncertainty? as to whether or not to use tranexamic acid in a particular patient with TBI |
Adultos (16 años o mayores) con traumatismo craneoencefálico (TCE): -que se hayan lesionado no más de ocho horas antes - con cualquier sangrado intracraneano en una tomografía computarizada o que tengan una ECG de 12 o menos y - que tienen sangrado extracraneal no significativo (con necesidad de transfusión de sangre inmediata) - El criterio fundamental de elegibilidad es la ?incertidumbre? del médico responsable acerca de si usar o no usar ácido tranexámico en un paciente en particular con un trauma craneano |
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E.4 | Principal exclusion criteria |
? Patients should not be randomised if the responsible clinician considers there is a clear indication for antifibrinolytic therapy ? Patients should not be randomised if the responsible clinician considers there is a clear contraindication for antifibrinolytic therapy |
Los pacientes no se deben aleatorizar si el médico responsable considere que existe una clara indicación para el tratamiento antifibrinolítico. Los pacientes no se deben aleatorizar si el médico responsable considere que existe una clara contraindicación para el tratamiento antifibrinolítico. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is death in hospital within 28 days of injury. Cause-specific mortality will also be recorded. |
La medida de resultado primario es la muerte en el hospital dentro de los 28 días de la lesión. También se valorará la causa de la muerte. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
28 days after randomisation or at death or hospital discharge if either happens sooner |
28 días después de la aleatorización o muerte o alta del hospital, lo que ocurra antes |
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E.5.2 | Secondary end point(s) |
(a)Vascular occlusive events (myocardial infarction, pulmonary embolism, clinical evidence of deep vein thrombosis) (b)Stroke (c)Disability assessed using the Disability Rating Scale and Patient Orientated Outcome measures (d)Seizures (e)Neurosurgical intervention (f)Days in intensive care (g)Other adverse events |
(a) eventos oclusivos vasculares (infarto de miocardio, embolia pulmonar, evidencia clínica de trombosis venosa profunda) (b) AVC
Discapacidad valorada usando la Escala de calificación de discapacidad y las medidas de Desenlaces orientados al paciente (d) Convulsiones (e) Intervención neuroquirúrgica (f) Días en cuidados intensivos (g) Se describirán otros eventos adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
28 days after randomisation or at death or hospital discharge if either happens sooner |
28 días después de la aleatorización o muerte o alta del hospital, lo que ocurra antes |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 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 | 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 |
Albania |
Argentina |
Bangladesh |
Cameroon |
Colombia |
Ecuador |
Egypt |
El Salvador |
Georgia |
Ghana |
India |
Indonesia |
Jamaica |
Kenya |
Mexico |
Nigeria |
Pakistan |
Spain |
Sudan |
Thailand |
Tunisia |
Uganda |
Ukraine |
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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After 10,000 patients have been recruited (anticipated to be completed by 31st December, 2016), the trial will end when follow up (max 28 days) of the last patient recruited is completed.
The trial may be terminated early by the Trial Steering Committee on the recommendation of the Independent Data Monitoring Committee on their interim reviews of the unblinded data. |
Tras la inclusión de 10.000 pacientes (proyectada para el 31 de Diciembre, 2016), el proceso terminará cuando el seguimiento (máximo 28 días) del último paciente reclutado se haya completado.
El estudio puede ser parado de forma anticipada por recomendación del Comité Independiente de Supervisión de datos en sus revisiones no ciegas planificadas como análisis intermedio. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 30 |