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.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
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.
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- Nem alkalmazható
Kapcsolatok és helyek
Tanulmányi kapcsolat
- Név: Wenbin Zhang, Dr.
- Telefonszám: 0571-86006241
- E-mail: wzhang_crf@126.com
Tanulmányi helyek
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Zhejiang
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Hangzhou, Zhejiang, Kína
- Sir Run Run Shaw Hospital
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Kapcsolatba lépni:
- Wenbin Zhang, Dr.
- Telefonszám: 0571-86006241
- E-mail: wzhang_crf@126.com
-
Kutatásvezető:
- Wenbin Zhang, Dr.
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-
Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
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.
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
|
Kísérleti: 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 |
|
Aktív összehasonlító: 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 |
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Major Adverse Cardiovascular Events Through 18 Months
Időkeret: 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
|
Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Key Safety Composite Event Through 18 Months
Időkeret: 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
Időkeret: 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
Időkeret: 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
|
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Nonfatal Ischemic Stroke Through 18 Months
Időkeret: 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
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Ischemia-Driven Revascularization Through 18 Months
Időkeret: From randomization through 18 months
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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
Időkeret: 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
Időkeret: 3, 6, 12, and 18 months
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Proportion of evaluated participants with fasting hs-CRP <1.0 mg/L at each scheduled assessment. |
3, 6, 12, and 18 months
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Proportion With hs-CRP <2.0 mg/L
Időkeret: 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
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Average Daily Colchicine Dose
Időkeret: From randomization through 18 months
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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
Időkeret: From randomization through 18 months
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Proportion of participants with at least one protocol-directed reduction in colchicine dose. |
From randomization through 18 months
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Colchicine Discontinuation
Időkeret: From randomization through 18 months
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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
Időkeret: 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
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Együttműködők és nyomozók
Szponzor
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- TARGET-CHD
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
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