Among patients with acute spontaneous supratentorial intracerebral hemorrhage, which treatment strategy: intravenous deferoxamine, low-dose oral colchicine, combination, or standard of care alone results in the greatest improvement in functional outcomes?

The study setting/ Study sites: Sri Jayewardenepura General Hospital, National Hospital of Sri Lanka, Kandy National Hospital, National Hospital – Galle and Colombo South Teaching Hospital.

If randomized – Randomisation will use minimisation method to minimise the imbalance between the number of patients in each treatment group over a number of factors including region, location (deep vs cortical), age (>65 vs <65 years old), sex (male vs female), time from onset (>6 vs <6 hours), haematoma volume (10-29 vs (>30 mL), receipt of any decompressive surgery (yes vs no), and intraventricular extension of ICH, etc.

Response Adaptive Randomisation (RAR) will also be used in this domain to allow readjustment of recruitment towards treatment arms with more favourable emerging effects. Randomisation will be centralized, secure and concealed, using a web-based server, thus eliminating the possibility of imbalance in baseline prognostic variables and confounding by allocation bias. Investigators will rapidly access the randomiser using a web browser/application accessible using a username and password secured via multi-factor authentication.

Intervention – Participants with ICH who are admitted to participating hospitals and meet the eligibility criteria for this domain will be randomised to receive one of four interventions to commence as soon as possible: • No deferoxamine mesylate and no colchicine (Control Group) • Deferoxamine mesylate only: deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) and continued for 2 consecutive days • Colchicine only: 0.5mg of oral colchicine daily for 30 days • Both deferoxamine mesylate and colchicine: deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) and continued for 2 consecutive days; plus 0.5mg of oral colchicine daily for 30 consecutive days

Timing and setting of intervention - The timing of administration of interventions is specified to be immediately after randomisation. Deferoxamine mesylate is to be administered at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) post-randomisation and continued for 2 consecutive days, in a high dependency area (e.g., acute stroke or neurosurgery care unit) or stroke ward as is usual for ICH patients. Colchicine is to be administered at a dose of 0.5mg daily for 30 consecutive days.

Standard therapy given in place of placebo is dependent on the patients usual care.

The trial will have allocation concealment and blinded endpoint assessment, but open-label treatment therefore no groups are blinded to the intervention. Given the time sensitive nature of acute stroke treatment, blinding the enrolling personnel to treatment assignment is not practical. Clinical site staff, including the Principal Investigator (PI), sub-investigators, clinic site staff, and the Sponsor will not be blinded to treatment allocated or received. In the event of an emergency the PI will be already unblinded. The trial will have blinded endpoint assessment on Day 90, with central blinded assessors contacting the participants.

• Adult (age (>18 and < 80 years) • Diagnosis of presumed spontaneous supratentorial intracerebral haemorrhage, confirmed by brain imaging • Presentation to hospital within 24 hours of symptom onset (or last seen well) • Haematoma volume >10 mL or any volume post-surgery • National Institute of Health Stroke Scale (NIHSS) score >8 • Glasgow coma scale (GCS) >8 • Provide written informed consent by patient (or approved surrogate)

• Secondary cause of haemorrhage (e.g., structural abnormality such as arteriovenous malformation, cerebral aneurysm, tumour, trauma), or haemorrhagic transformation of acute ischaemic stroke • Isolate intraventricular haemorrhage • Chronic Kidney Disease • Very high likelihood of death within 7 days or poor adherence to study treatment or follow-up • Severe comorbid disease that will interfere with outcome assessments (e.g., cancer, chronic airflow disease, heart failure, significant disability) • Women who are pregnant or lactating

Exclusion criteria related to use of deferoxamine: • Previous chelation therapy or known hypersensitivity to deferoxamine products; • Severe iron deficiency anaemia (haemoglobin <7 g/dL or requiring regular blood • transfusions); • Regular iron supplementation containing >325 mg of ferrous iron; • Serum creatinine >2 mg/dL; • Patients with known heart failure taking >500 mg of vitamin C Exclusion criteria related to use of colchicine: • Allergic to colchicine • Myelodysplastic hypoplasia, or liver or severe renal failure • Use of medication which may interact with colchicine (strong CYPsA4 inhibitors [e.g., ketoconazole] and strong P-glycoprotein inhibitors [e.g., fluconazole])