The Fifth INTEnsive pReventing Secondary Injury in Acute Cerebral Haemorrhage Trial Within ACT-GLOBAL
The George Institute
2,000 participants
Feb 27, 2025
INTERVENTIONAL
Conditions
Summary
This is a domain within the ACT-GLOBAL platform trial to compare the effectiveness of early and appropriate pharmacological interventions in acute intracerebral hemorrhage (ICH) to control secondary brain injury. Up to 2000 patients with presumed spontaneous supratentorial intracerebral hemorrhage (ICH) will be followed for 6 months (or death, if prior to 6 months). Adaptive interim analyses will be used, with statistical triggers to determine if any of the interventions are superior to control. The end of the trial is defined as the date that all participants have completed their 6-month assessment. A large amount of preclinical data indicates that the outcome from ICH is linked to the detrimental effects of breakdown substances from brain bleeds. However, there remains a lack of compelling evidence supporting the effectiveness of any pharmacological intervention that can mitigate the secondary cerebral injury. The INTERACT domain aims to assess the effectiveness of intravenous deferoxamine and low-dose oral colchicine, both individually and in combination, to standard of care alone, on improving functional outcome in patients with spontaneous supratentorial ICH. Those patients who meet eligibility criteria will be randomized to receive one of four interventions: 1. No deferoxamine mesylate and no colchicine (labeled as control) 2. Deferoxamine mesylate only: deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) post-randomization and continue for the following 2 consecutive days. 3. Colchicine only: 0.5mg of oral colchicine daily for 30 consecutive days. 4. Both deferoxamine mesylate and colchicine: deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) post-randomization and continue for the following 2 consecutive days; plus 0.5mg of oral colchicine daily for 30 consecutive days.
Eligibility
Inclusion Criteria7
- Age between 18 and 80 years old
- Diagnosis of presumed spontaneous supratentorial intracerebral haemorrhage, confirmed by brain imaging
- Presentation to hospital within 24 hours of symptom onset (or last seen well)
- Hematoma volume ≥10 mL or any volume post-surgery
- NIHSS score >8
- GCS ≥8
- Provide written informed consent by patient (or approved surrogate)
Exclusion Criteria14
- 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
- Previous chelation therapy or known hypersensitivity to deferoxamine products;
- Severe iron deficiency anaemia (haemoglobin <7 g/dL or requiring regular blood transfusions);
- Taking iron supplements containing >325 mg of ferrous iron;
- Serum creatinine >2 mg/dL;
- Patients with known heart failure taking >500 mg of vitamin C
- Allergic to colchicine
- Myelodysplastic hypoplasia, or liver or severe renal failure
- Use of medication which may interact with colchicine (e.g., strong CYPsA4 inhibitors such as ketoconazole, strong P-glycoprotein inhibitors such as fluconazole)
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Interventions
The intervention group will receive 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.
The intervention group will receive deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) and continued for 2 consecutive days
The group will not receive deferoxamine mesylate or colchicine
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06763055