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.
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
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
Factorial
Colchicine 0.5 mg
DrugThe intervention group will receive 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.
Deferoxamine Mesylate
DrugThe 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
Control (Standard treatment)
Other interventionThe group will not receive deferoxamine mesylate or colchicine
mRS scores at 6 months analysed with utility-weights
Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favorable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
Excellent functional neurological outcome (mRS 0-1) at 6 months
Modified Rankin Scale (mRS) with scores of 0 to 1 indicating a favorable outcome without or with symptoms but no disability.
Independent functional neurological outcome (mRS 0-2) at 6 months
Modified Rankin Scale (mRS) with scores of 2 to 5 indicating increasing levels of disability (and dependency).
Health-related quality of life, as measured by the EQ-5D-5L at month 6
The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The version of the instrument selected for the trial is interviewer administered either in-person, or by telemedicine or by telephone. The respondents will also rate their overall health on the day of the interview on a 0-100 visual analogue scale (EQ-VAS).
Ordinal shift in the 7 levels of mRS at 6 months
Modified Rankin Scale (mRS) in which scores of 0 to 1 indicate a favorable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
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The George Institute
Lead sponsor
University of Calgary
Collaborator
