Hs-CRP-Guided Colchicine Treatment Targets in Very-High-Risk Patients With Coronary Artery Disease After PCI (TARGET-CHD)
Colchicine Titration Guided by Hs-CRP Targets on Cardiovascular Events in Very-High-Risk Coronary Heart Disease Patients After PCI: A Multicenter, Randomized, Open-Label, Noninferiority Trial
This multicenter, randomized, open-label, noninferiority trial will compare two high-sensitivity C-reactive protein (hs-CRP) target-guided colchicine strategies in 1,768 adults with very-high-risk coronary artery disease after percutaneous coronary intervention, LDL cholesterol ≤1.4 mmol/L, and residual inflammation (hs-CRP 2.0-10.0 mg/L). Participants will be assigned 1:1 to a standard target of 1.0 to <2.0 mg/L or an intensive target of <1.0 mg/L. Both groups will start colchicine 0.25 mg orally once daily, with dose adjustments guided by hs-CRP and tolerability. The primary outcome is the 18-month composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or ischemia-driven revascularization. The noninferiority hypothesis compares the standard target strategy with the intensive target strategy, with a prespecified hazard-ratio margin of 1.30.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Adults with coronary artery disease after PCI who meet very-high-risk atherosclerotic cardiovascular disease criteria, have fasting LDL cholesterol ≤1.4 mmol/L within 1 month, and have fasting hs-CRP 2.0-10.0 mg/L within 7 days before enrollment will be randomized through a central system. Randomization is stratified by center, baseline hs-CRP (<5 vs ≥5 mg/L), and age (<65 vs ≥65 years). All participants continue standard coronary disease care and start colchicine 0.25 mg orally daily. At 1 month, the intensive group maintains the dose when hs-CRP is <1.0 mg/L or, if tolerated, increases to 0.5 mg daily otherwise. The standard group reduces to 0.25 mg every other day if hs-CRP is <1.0 mg/L, continues 0.25 mg daily if hs-CRP is 1.0 to <2.0 mg/L, or, if tolerated, increases to 0.5 mg daily if hs-CRP is ≥2.0 mg/L. Participants who increase to 0.5 mg daily undergo repeat assessment after another month. If the assigned target remains unmet after one month at 0.5 mg daily, protocol-directed colchicine is stopped while clinical and safety follow-up continues under the original randomized assignment. Doses may be reduced or treatment stopped for adverse reactions; interruptions may occur during acute infection or elective surgery. Follow-up assessments occur at 1, 3, 6, 12, and 18 months, with an additional 2-month assessment for participants whose dose was increased at 1 month. An independent blinded clinical events committee adjudicates events.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Wenbin Zhang, Dr.
- Número de telefone: 0571-86006241
- E-mail: wzhang_crf@126.com
Locais de estudo
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Zhejiang
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Hangzhou, Zhejiang, China
- Sir Run Run Shaw Hospital
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Contato:
- Wenbin Zhang, Dr.
- Número de telefone: 0571-86006241
- E-mail: wzhang_crf@126.com
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Investigador principal:
- Wenbin Zhang, Dr.
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-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Age ≥18 years.
- Diagnosed coronary artery disease and prior percutaneous coronary intervention.
- Very-high-risk atherosclerotic cardiovascular disease, defined as at least two major ASCVD events or one major ASCVD event plus at least two high-risk conditions according to the 2023 Chinese lipid management guideline.
- Fasting LDL cholesterol ≤1.4 mmol/L measured within 1 month before enrollment.
- Fasting hs-CRP 2.0-10.0 mg/L measured within 7 days before enrollment, without a recent infection, surgery, trauma, or other acute inflammatory condition.
- Voluntary written informed consent.
Exclusion Criteria:
- Contraindication or allergy to colchicine, or colchicine use within the prior 4 weeks.
- ALT or AST >3 times the upper limit of normal, or eGFR <30 mL/min/1.73 m².
- Acute gout flare, serious infection requiring intravenous antibiotics, major surgery, or major trauma within the preceding 3 months.
- Malignancy with expected survival <18 months, autoimmune disease, ongoing immunosuppressive treatment, or chronic active infection such as active tuberculosis or hepatitis.
- Critical illness, psychiatric illness or cognitive impairment affecting informed participation, or pregnancy, as specified among excluded vulnerable groups in the protocol.
- Strong CYP3A4/P-glycoprotein inhibitor (e.g., clarithromycin, itraconazole, cyclosporine, verapamil) or moderate inhibitor (e.g., erythromycin, fluconazole) within 1 month before enrollment.
- Concurrent participation in another interventional clinical study.
- Any other reason the investigator considers the participant unsuitable.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Standard hs-CRP Target (1.0 to <2.0 mg/L)
Colchicine 0.25 mg orally once daily at initiation, with hs-CRP-guided adjustments to target 1.0 to <2.0 mg/L. At 1 month, reduce to 0.25 mg every other day if hs-CRP <1.0 mg/L; maintain 0.25 mg daily if 1.0 to <2.0 mg/L; or, if tolerated, increase to 0.5 mg daily if ≥2.0 mg/L. If the target remains unmet after one month at 0.5 mg daily, stop protocol-directed colchicine and continue endpoint/safety follow-up. Dose reduction or discontinuation is permitted for adverse reactions. |
Oral colchicine 0.25 mg daily initially, titrated or reduced according to hs-CRP target 1.0 to <2.0 mg/L and tolerability, with a maximum of 0.5 mg daily Oral colchicine 0.25 mg daily initially, titrated according to hs-CRP target <1.0 mg/L and tolerability, with a maximum of 0.5 mg daily |
|
Comparador Ativo: Intensive hs-CRP Target (<1.0 mg/L)
Colchicine 0.25 mg orally once daily at initiation, with hs-CRP-guided adjustments to target <1.0 mg/L. At 1 month, maintain 0.25 mg daily if hs-CRP <1.0 mg/L; otherwise, if tolerated, increase to 0.5 mg daily. If the target remains unmet after one month at 0.5 mg daily, stop protocol-directed colchicine and continue endpoint/safety follow-up. Dose reduction or discontinuation is permitted for adverse reactions. |
Oral colchicine 0.25 mg daily initially, titrated or reduced according to hs-CRP target 1.0 to <2.0 mg/L and tolerability, with a maximum of 0.5 mg daily Oral colchicine 0.25 mg daily initially, titrated according to hs-CRP target <1.0 mg/L and tolerability, with a maximum of 0.5 mg daily |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Major Adverse Cardiovascular Events Through 18 Months
Prazo: From randomization through 18 months
|
Time to first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or ischemia-driven coronary revascularization. The primary noninferiority comparison is the hazard ratio for the standard hs-CRP target strategy versus the intensive hs-CRP target strategy, with a prespecified margin of 1.30; events are adjudicated by an independent blinded clinical events committee. |
From randomization through 18 months
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Key Safety Composite Event Through 18 Months
Prazo: From randomization through 18 months
|
Time to first occurrence of CTCAE grade ≥3 gastrointestinal adverse reaction, symptomatic creatine kinase elevation or rhabdomyolysis, ≥30% decline in estimated glomerular filtration rate, or drug-related serious adverse event. A superiority comparison of the two randomized strategies is prespecified; the direction and multiplicity sequence must match the final protocol |
From randomization through 18 months
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Cardiovascular Death Through 18 Months
Prazo: From randomization through 18 months
|
Time to cardiovascular death, as adjudicated by the blinded clinical events committee. Time Frame: From randomization through 18 months |
From randomization through 18 months
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Nonfatal Myocardial Infarction Through 18 Months
Prazo: From randomization through 18 months
|
Time to nonfatal myocardial infarction as defined in the protocol and adjudicated by the blinded clinical events committee. |
From randomization through 18 months
|
|
Nonfatal Ischemic Stroke Through 18 Months
Prazo: From randomization through 18 months
|
Time to nonfatal ischemic stroke as defined in the protocol and adjudicated by the blinded clinical events committee. |
From randomization through 18 months
|
|
Ischemia-Driven Revascularization Through 18 Months
Prazo: From randomization through 18 months
|
Time to PCI or coronary bypass surgery performed because of ischemic symptoms or objective evidence of myocardial ischemia |
From randomization through 18 months
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Change in hs-CRP From Baseline
Prazo: Baseline and 3, 6, 12, and 18 months
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Change in fasting hs-CRP concentration from baseline, expressed in mg/L, at each scheduled follow-up assessment. |
Baseline and 3, 6, 12, and 18 months
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Proportion With hs-CRP <1.0 mg/L
Prazo: 3, 6, 12, and 18 months
|
Proportion of evaluated participants with fasting hs-CRP <1.0 mg/L at each scheduled assessment. |
3, 6, 12, and 18 months
|
|
Proportion With hs-CRP <2.0 mg/L
Prazo: 3, 6, 12, and 18 months
|
Proportion of evaluated participants with fasting hs-CRP <2.0 mg/L at each scheduled assessment. |
3, 6, 12, and 18 months
|
|
Average Daily Colchicine Dose
Prazo: From randomization through 18 months
|
Average administered daily colchicine dose in milligrams over the treatment period; exact denominator and handling of interruptions to be specified in the statistical analysis plan. |
From randomization through 18 months
|
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Colchicine Dose Reduction
Prazo: From randomization through 18 months
|
Proportion of participants with at least one protocol-directed reduction in colchicine dose. |
From randomization through 18 months
|
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Colchicine Discontinuation
Prazo: From randomization through 18 months
|
Proportion of participants who permanently discontinue protocol-directed colchicine, with reasons recorded |
From randomization through 18 months
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Cumulative Colchicine Exposure Duration
Prazo: From randomization through 18 months
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Total number of days taking colchicine during study follow-up; interruptions and discontinuations are recorded. |
From randomization through 18 months
|
Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
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Outros números de identificação do estudo
- TARGET-CHD
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