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

NCT06763055 | Recruiting Phase 3 DMC

• 1 other identifier: ACT-GLOBAL_ICH_01
• Study Type: interventional
• Target: 2,000
• Locations: 2 countries
• Sites: 2

Brief 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. 1.No deferoxamine mesylate and no colchicine (labeled as control)
2. 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. 3.Colchicine only: 0.5mg of oral colchicine daily for 30 consecutive days.
4. 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.

Conditions

Intracerebral Hemorrhage; Spontaneous Intracerebral Hemorrhage; Supratentorial Intracerebral Haemorrhage; Acute Intracerebral Haemorrhage; Acute Stroke

Keywords

Stroke; Acute Stroke; ICH; Intracerebral Hemorrhage; Platform Trial; Adaptive Platform Trial; Supratentorial ICH; secondary brain injury; deferoxamine mesylate; colchicine

Outcome Measures

Primary Outcomes (1)

• 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.

  From enrollment to the 6 month assessment

Secondary Outcomes (10)

• 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)

Study Arms (4)

No deferoxamine mesylate, No colchicine (control)

PLACEBO COMPARATOR

The group will not receive deferoxamine mesylate or colchicine

Other: Control (Standard treatment)

Deferoxamine mesylate only

ACTIVE COMPARATOR

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.

Drug: Deferoxamine Mesylate

Colchicine only

ACTIVE COMPARATOR

The intervention group will receive 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.

Drug: Colchicine 0.5 mg

Both deferoxamine mesylate and colchicine

ACTIVE COMPARATOR

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.

Drug: Colchicine 0.5 mg; Drug: Deferoxamine Mesylate

Interventions

Colchicine 0.5 mg DRUG

The intervention group will receive 0.5mg of oral colchicine daily as soon as possible after randomization, to continue for 30 days.

Both deferoxamine mesylate and colchicine; Colchicine only

Deferoxamine Mesylate DRUG

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

Also known as: Yes DX

Both deferoxamine mesylate and colchicine; Deferoxamine mesylate only

Control (Standard treatment) OTHER

The group will not receive deferoxamine mesylate or colchicine

No deferoxamine mesylate, No colchicine (control)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• The George Institute: lead
• University of Calgary: collaborator

Study Sites (2)

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Conditions

Cerebral Hemorrhage; Stroke

Interventions

Colchicine; Deferoxamine

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids

Central Study Contacts

Xiaoying Chen, PhD BPharm BMgt

CONTACT

4039448107; xchen@georgeinstitute.org.au

Craig Anderson, MD

CONTACT

4039448107; canderson@georgeinstitute.org.au

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The INTERACT5 Domain includes two treatments provided in a factorial manner, creating four different treatment arms. The two treatments are: A. Intravenous deferoxamine mesylate (abbreviated as DX) B. Low-dose oral colchicine (abbreviated as OC) The four arms including three interventions and one control in the domain are the 2x2 factorial of each treatment/no treatment. The one control arm and three intervention arms in the domain are: 1. No DX and No OC (labeled as Control) 2. Yes DX and No OC 3. No DX and Yes OC 4. Yes DX and Yes OC

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: January 8, 2025
• Study Start: February 27, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CN (1)