E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild traumatic brain injury. |
|
E.1.1.1 | Medical condition in easily understood language |
Bleeding into the brain because of a head injury. |
|
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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060690 |
E.1.2 | Term | Traumatic brain injury |
E.1.2 | System Organ Class | 100000004863 |
|
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 |
The CRASH-4 trial will see if a drug called tranexamic acid can prevent bleeding into the brain from happening when injected into the muscle of older adults soon after a mild Traumatic Brain Injury (TBI). We hope that this will lead to better health outcomes. We will see if giving tranexamic acid early has an effect on the number of patients discharged from the emergency department within 24 hours of arrival. |
|
E.2.2 | Secondary objectives of the trial |
We will see if giving tranexamic acid early by injection into the muscle of older adults soon after a mild Traumatic Brain Injury (TBI) leads to better health outcomes such as reduced bleeding into the brain (shown on a brain scan), fewer deaths, reduced disability, fewer days in intensive care, fewer surgical interventions, fewer re-admissions to hospital within 28 days and better outcomes at 1 year. We will assess check if there is any increase in serious side effects including heart attack, stroke, blood clots in the legs or lungs, seizures, pneumonia, injection site reactions or any other adverse events. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 70 years or older (actual or estimated) • History or evidence of head injury (e.g. laceration, bruise, swelling or pain in head or face) • GCS ≥ 13 • Has one or more of the following symptoms: o has or had any impaired consciousness (loss of consciousness, amnesia, or confusion) o nausea or vomiting • Within 3 hours of injury (do not include if y interval cannot be estimated e.g. patient unable to confirm time of fall or patient found on floor after an unwitnessed fall and home alone) • Patient will be conveyed or is admitted to a participating hospital
Exclusion: • Living in a nursing home, mental health institution or prison • TXA is clearly indicated (e.g. major bleeding) or contraindicated (e.g. suspected stroke) • Known to have a diagnosis of dementia |
|
E.4 | Principal exclusion criteria |
• Living in a nursing home, mental health institution or prison • TXA is clearly indicated (e.g. major bleeding) or contraindicated (e.g. suspected stroke) • Known to have a diagnosis of dementia |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is discharge from the emergency department within 24 hours of arrival. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients’ outcomes will be assessed in-hospital at discharge, death, or 28 days after randomisation, whichever occurs first. |
|
E.5.2 | Secondary end point(s) |
Intracranial bleeding on CT scan, death, disability, global assessment of ability to self-care, patient management, re-admission to hospital, pre-specified adverse events, other adverse events, dementia |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The Outcome Form will be used to collect short term (in-hospital) outcomes at discharge, death, or 28 days after randomisation. Long term outcomes on dementia incidence will be collected one year after randomisation by data linkage using the UK NHS Hospital Episodes Statistics (HES) via NHS Digital, or using NHS Wales Informatics Service. |
|
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 | 200 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
The trial will end when NHS Digital / NWIS provide the 1-year follow-up data for the final randomised patient. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 | 28 |