Colchicine for Reducing Dependency and MACE in Acute Intracerebral Hemorrhage Survivors with Atherosclerotic Risk: Randomized Placebo-Controlled Trial

The primary objective is to determine whether oral colchicine 0.5 mg daily, initiated within 72 hours of symptom onset, is superior to placebo in reducing dependency and major vascular events among survivors of spontaneous intracerebral hemorrhage who have documented atherosclerotic disease or risk factors, thereby addressing a critical gap in post‑hemorrhagic secondary prevention.

Secondary objectives include evaluation of:

• Functional outcome
• Cognitive outcome
• Quality of life

The trial enrolled 813 participants, comprising both female and male patients with documented spontaneous intracerebral hemorrhage occurring within 72 hours of symptom onset. Eligible individuals were required to have evidence of atherosclerosis, defined by a history of symptomatic coronary, peripheral or carotid artery disease, imaging‑confirmed extracranial or intracranial atherosclerotic lesions, or the presence of at least two risk factors such as age ≥60 years, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease (eGFR 15–50 mL/min), prior ischemic stroke, or current smoking. Participants were selected from the patient population meeting these criteria and capable of providing signed informed consent, either directly or through a legally authorized representative. The cohort represented adult age groups corresponding to protocol codes 3 and 4, encompassing middle‑aged to older adults, and was generally in stable health apart from the qualifying hemorrhagic event and associated atherosclerotic conditions. Lifestyle considerations such as smoking status were incorporated as part of the risk‑factor assessment.

The CoVasc-ICH2 study is a phase III double‑blind, randomized, placebo‑controlled trial evaluating oral colchicine 0.5 mg daily versus matching placebo in survivors of spontaneous intracerebral hemorrhage who have evidence or risk factors for atherosclerosis. Eligible participants are screened within 72 hours of symptom onset, provide informed consent, and are randomized at the baseline visit to receive either colchicine Aspire 0.5 mg tablets or an identical placebo tablet. Study medication is administered orally once daily for a six‑month treatment period. Follow‑up visits are scheduled to collect safety data, assess adherence, and evaluate efficacy outcomes, culminating in an end‑of‑study visit at six months after randomization. The primary efficacy assessment is a hierarchical composite endpoint that incorporates major cardiovascular events and dependency, the latter defined by a modified Rankin Scale score of 3–5 at six months; secondary assessments include functional, cognitive, and quality‑of‑life measures. Participant involvement therefore extends from the screening visit through the six‑month end‑of‑study assessment, with a total duration of approximately six months per enrollee.

The investigational product is colchicine Aspire 0.5 mg tablets, an oral tablet formulation containing 0.5 mg of colchicine per tablet. The medication is administered by mouth once daily, with the first dose to be taken within 72 hours after onset of acute intracerebral hemorrhage and continued for the duration of the study treatment period.

The comparator is a matching placebo tablet containing no active pharmaceutical ingredient. The placebo tablet is identical in appearance to the active tablet and is also taken orally once daily on the same schedule as the investigational product.

Dosing is scheduled daily at a consistent time to maintain steady exposure. Compliance is monitored through pill counts performed at each study visit, participant dosing diaries, and verification of medication adherence during scheduled assessments. Any missed doses are recorded, and participants receive reminders to enhance adherence to the prescribed regimen.

Efficacy will be evaluated using a Hierarchical composite endpoint (HCE) that integrates major cardiovascular events and functional dependency. The composite includes time‑to first stroke (ischemic, hemorrhagic or undefined), time‑to cardiovascular death, dependency defined as a modified Rankin Scale score of 3–5 at 6 months post‑randomization, time‑to first myocardial infarction, and time‑to first revascularization procedure for coronary, carotid, or peripheral arterial disease. Secondary efficacy measures comprise functional outcome at 6 months (modified Rankin Score), cognitive outcome at study completion assessed with the telephone Montreal Cognitive Assessment (T-MoCA) and the telephone Mental Alternation Test (t-MAT), health‑related quality of life measured by the EQ-5D-5L questionnaire, and the incidence of disabling or fatal stroke during follow‑up evaluated with the modified Rankin Scale.

Time‑to event data will be captured prospectively at scheduled study visits and through standardized adverse‑event reporting forms. The modified Rankin Scale assessment will be performed by trained investigators at the 6‑month visit and at the final study visit. Cognitive assessments (T‑MoCA and t‑MAT) will be administered by telephone using validated protocols at the end of the study period. Quality‑of‑life data will be collected via the EQ‑5D‑5L questionnaire at study completion. All efficacy parameters will be analyzed according to the predefined statistical plan, employing survival analysis for time‑to event components and appropriate comparative tests for ordinal and continuous secondary endpoints.