The Fifth INTEnsive pReventing Secondary Injury in Acute Cerebral Haemorrhage Trial Within ACT-GLOBAL
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 2
- 主要终点
- mRS scores at 6 months analysed with utility-weights
研究概览
简要总结
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:
- No deferoxamine mesylate and no colchicine (labeled as control)
- 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.
- Colchicine only: 0.5mg of oral colchicine daily for 30 consecutive days.
- 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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The trial will have allocation concealment and blinded endpoint assessment, but open-label treatment. 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.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Provide written informed consent by patient (or approved surrogate)
排除标准
- •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);
- •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
- •Exclusion criteria related to the use of colchicine:
- •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)
研究组 & 干预措施
No deferoxamine mesylate, No colchicine (control)
The group will not receive deferoxamine mesylate or colchicine
干预措施: Control (Standard treatment) (Other)
Colchicine only
The intervention group will receive 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.
干预措施: Colchicine 0.5 mg (Drug)
Both deferoxamine mesylate and colchicine
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; plus 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.
干预措施: Colchicine 0.5 mg (Drug)
Deferoxamine mesylate only
The intervention group will receive deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) of randomization and continued for 2 consecutive days.
干预措施: Deferoxamine Mesylate (Drug)
Both deferoxamine mesylate and colchicine
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; plus 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.
干预措施: Deferoxamine Mesylate (Drug)
结局指标
主要结局
mRS scores at 6 months analysed with utility-weights
时间窗: From enrollment to the 6 month assessment
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.
次要结局
- Excellent functional neurological outcome (mRS 0-1) at 6 months(From enrollment to the 6 month assessment)
- Independent functional neurological outcome (mRS 0-2) at 6 months(From enrollment to the 6 month assessment)
- Health-related quality of life, as measured by the EQ-5D-5L at month 6(Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner))
- Ordinal shift in the 7 levels of mRS at 6 months(Done at the 6-month assessment (assessed in a blinded manner))
- Disability (mRS 3-5) at 6 months(Done at the 6-month assessment (assessed in a blinded manner))
- NIHSS score at Day 7 and Day 14 (or discharge if earlier)(Assessment performed at Day 7 and Day 14 (or discharge if earlier))
- PHE at Day 7 and Day 14 (or discharge if earlier)(Day 7 and Day 14 (or discharge if earlier))
- Total length of initial hospital stay(Within 6 months after stroke onset)
- Ambulatory status at hospital discharge(At the time when patient is discharged from enrolling hospital, within 6 months after stroke onset)
- Place of residence at 6 months(Completed at the 6-month follow-up visit)