Tranexamic acid for hyperacute primary intracerebral haemorrhage (TICH-3) and Desmopressin for reversal of Antiplatelet drugs in Stroke due to haemorrhage (DASH)-2
Hyperacute primary intracerebral haemorrhage (stroke)
Current interventions as of 23/02/2026: Pragmatic phase III prospective blinded randomised placebo-controlled trial performed in two phases: a 30-month internal pilot phase with pre-specified progression criteria then the main phase. Using a pragmatic design with emergency consent processes, simple randomisation and minimal data collection will optimise enrolment and the blinded design will minimise bias. Master Protocol (TICH-3) Participants are randomised to receive intravenous TXA 2 g given as 1 g bolus in 100 ml normal saline 0.9% infusion over 10 min and 1 g infusion in 250 ml normal saline 0.9% over 8 hours or a placebo (normal saline 0.9%) administered by an identical regimen. Randomisation will be to TXA vs placebo in a 1:1 ratio. Optional sub-study (DASH-2) where participants are randomised to receive intravenous desmopressin given as 20 μg in 50 ml Sodium Chloride 0.9% over 20 minutes or a placebo (normal saline 0.9%) administered by an identical regimen. Randomisation will be to desmopressin vs placebo in a 1:1 ratio. _____ Previous interventions: Pragmatic phase III prospective blinded randomised placebo-controlled trial performed in two phases: a 30-month internal pilot phase with pre-specified progression criteria then the main phase. Using a pragmatic design with emergency consent processes, simple randomisation and minimal data collection will optimise enrolment and the blinded design will minimise bias. Participants are randomised to receive intravenous TXA 2 g given as 1 g bolus in 100 ml normal saline 0.9% infusion over 10 min and 1 g infusion in 250 ml normal saline 0.9% over 8 hours or a placebo (normal saline 0.9%) administered by an identical regimen. Randomisation will be to TXA vs placebo in a 1:1 ratio.
Current key inclusion criteria as of 23/02/2026: TICH-3: Adult patients with ICH confirmed on brain imaging within 4.5 hours of symptom onset DASH-2: Adult patients taking antiplatelets with ICH confirmed on brain imaging within 24 hours of symptom onset _____ Previous key inclusion criteria: Adult patients with ICH confirmed on brain imaging within 4.5 hours of symptom onset
Current key exclusion criteria as of 23/02/2026: TICH-3 comparison: 1. Patient with a known indication for TXA treatment (e.g. traumatic brain injury) 2. Patient with contraindication for TXA treatment 3. Patient known to be taking therapeutic anticoagulation with warfarin or low molecular weight heparin at the time of enrolment. Patients taking direct oral anticoagulants can be included and are not excluded. 4. Massive ICH for which haemostatic treatment seems futile (This would ordinarily be when haematoma volume is estimated as larger than 60ml) 5. Severe coma (Glasgow Coma Scale <5) 6. Decision was already taken for palliative (end of life) care with the withdrawal of active treatment DASH-2 comparison: 1. Massive ICH for which haemostatic treatment seems futile (This would ordinarily be when haematoma volume is estimated as larger than 60ml (+/-10%)) 2. Aneurysmal subarachnoid haemorrhage 3. Haemorrhage known to be due to transformation of infarction 4. Haemorrhage known to be due to a thrombolytic drug, 5. Haemorrhage known to be due to venous thrombosis, 6. Risk/s of fluid retention associated with desmopressin judged clinically significant by the attending physician (for example patients with pulmonary oedema and/or cardiac failure), 7. Significant hypotension (systolic blood pressure <90mmHg), 8. Known drug-eluting coronary artery stent in previous three months, 9. Known unstable angina or acute coronary syndrome in past month, 10. Known allergy to desmopressin, 11. Pregnant or breast-feeding, 12. Life expectancy less than four hours, or planned for palliative care only 13. Glasgow coma scale less than 5. 14. Use of substances that are known to induce syndrome of inappropriate ADH section (SIADH), for example, tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect leading to increased rick of water retention and/or hyponatremia. _____ Previous participant exclusio