NCT06763055

The Fifth INTEnsive pReventing Secondary Injury in Acute Cerebral Haemorrhage Trial Within ACT-GLOBAL

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,000 (estimated)
• Sponsor: The George Institute · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Intracerebral hemorrhage (ICH) is a severe type of stroke, responsible for substantial disability and death worldwide. It accounts for 6.5% to 19.6% of all strokes, with incidence rates increasing, especially in low- and middle-income countries. Survivors often face significant consequences, including functional impairments, recurrent strokes, cognitive decline, and depression. Despite advancements in acute stroke care, there are few effective treatments specifically targeting the brain damage caused by ICH. Previous research has identified that the formation of perihaematomal oedema (PHE) is a critical factor in poor recovery, making it a key focus for therapeutic development. INTERACT5 domain will focus on two promising medications. Deferoxamine, an iron-chelating agent, targets oxidative stress caused by iron released from damaged brain tissue. Studies suggest it may reduce brain swelling and secondary injury after ICH. Colchicine, an anti-inflammatory medication, inhibits pathways involved in inflammation, which may help minimize brain damage. INTERACT5 will enroll patients aged 18-80 with acute spontaneous supratentorial ICH, confirmed through imaging, who present to the hospital within 24 hours of symptom onset. Other domain-specific inclusion criteria: * Hematoma volume ≥≥10 mL or any volume post-surgery * NIHSS score \>8 * GCS ≥8\>7 Participants will be randomized to one of four groups: standard care, deferoxamine alone, colchicine alone, or both treatments combined. Deferoxamine will be administered intravenously (32 mg/kg/day within 1 hour and continued for 2 consecutive days), and colchicine will be given orally (0.5 mg daily for 30 days). The study's primary outcome is the improvements in functional outcomes at 6 months, measured by the modified Rankin Scale (mRS). Secondary outcomes include EQ-5D-5L at 6 months, changes in PHE size, NIHSS scores, length of hospital stay, ambulatory status at discharge and safety indicators such as mortality at 6 months/SAEs to 6 month, kidney and liver function. Response Adaptive Randomization (RAR) will be used in this domain to allow readjustment of recruitment towards treatment arms with more favorable emerging effects. Randomization will use minimization method to minimize 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.

Conditions

• Intracerebral Hemorrhage
• Spontaneous Intracerebral Hemorrhage
• Supratentorial Intracerebral Haemorrhage
• Acute Intracerebral Haemorrhage
• Acute Stroke

Interventions

Type	Name	Description
DRUG	Colchicine 0.5 mg	The intervention group will receive 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.
DRUG	Deferoxamine Mesylate	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
OTHER	Control (Standard treatment)	The group will not receive deferoxamine mesylate or colchicine

Timeline

• Start date: 2025-02-27
• Primary completion: 2028-01-01
• Completion: 2028-01-01
• First posted: 2025-01-08
• Last updated: 2025-04-10

Locations

2 sites across 2 countries: Australia, China