BRAINapt – TBI International Adaptative Platform Trial
Traumatic brain injury
Current interventions as of 03/06/2026: Beta-Blockers Domain: Domain-Specific Exclusion Criteria: Contraindications to beta-blockers as per treating physician. Intervention Arms: Participants will be randomly assigned in a 2:2:3 ratio to one of three arms: 1. Propranolol Generic drug name: propranolol. Dosage and administration: As per ICU protocol at sites; enteral (PO or by feeding tube). Recommended initial daily dose 40 mg (10 mg q 6 h). Recommended target daily dose 80 mg (20 mg q 6 h). Recommended maximal daily dose 160 mg (40 mg q 6 h). Frequency: As clinically indicated. Recommended frequency in divided doses every 6, 8 or 12 hours Duration: From randomization until ICU discharge, death, or withdrawal of life-sustaining therapies. 2. Metoprolol Generic drug name: metoprolol. Dosage and administration: As per ICU protocol at sites; enteral (PO or by feeding tube). Recommended initial daily dose 50 mg (25 mg q 12 h). Recommended target daily dose 100 mg (50 mg q 12 h). Recommended maximal daily dose 200 mg (100 mg q 12 h). Frequency: As clinically indicated. Recommended frequency in divided doses every 12 hours Duration: From randomization until ICU discharge, death, or withdrawal of life-sustaining therapies. 3. Control (No beta-blocker) Participants receive standard ICU care without beta-blockers. Follow-up and duration: Participants are followed for 6 months post-randomization. Domain-specific secondary outcome: Day 28: myocardial ischemic events. Anticonvulsants Domain: Domain-Specific Exclusion Criteria: contraindications to anticonvulsants per treating physician; pre-existing anticonvulsant therapy for seizure disorder; early seizure requiring anticonvulsants; more than 72 hours elapsed since ICU admission. Intervention Arms: Participants will be randomly assigned in a 2:2:3 ratio to one of three arms: 4. Phenytoin Generic drug name: phenytoin. Dosage and administration: As per local ICU clinical protocols at sites; enteral (PO or by feeding tube) or IV
1. Adults aged ≥18 years 2. Admitted to the intensive care unit following acute TBI 3. Moderate or severe acute TBI (GCS ≤12 [on a scale of 3 to 15]) Each domain may have additional inclusion criteria
Platform trial exclusion criteria: 1. A decision to withdraw life-sustaining therapies was made Domain exclusion criteria: Beta-blocker domain: 1. Contraindications to use beta-blockers based on clinical risk (as per treating physician) Anticonvulsant domain: 1. Contraindications to use anticonvulsants based on clinical risk (as per treating physician) 2. Patient on anticonvulsants for seizure disorder prior to hospital admission 3. Early seizure requiring anticonvulsants 4. More than 72 hours have elapsed since ICU admission