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Effect van Colchicine op de Progressie van Coronaire Atherosclerose bij Patiënten met een TET2-CHIP Variant
Effect van Colchicine op de Progressie van Coronaire Atherosclerose bij Patiënten met TET2-CHIP Variant: een Pilot Klinische Studie (COLCHIP-Pilot)
This study aims to investigate whether TET2-associated clonal hematopoiesis of indeterminate potential (TET2-CHIP) can serve as a biomarker to guide precision use of colchicine in a population of clinically stable post-ACS patients receiving standard of care (SoC) therapy. Specifically, we will evaluate whether TET2-CHIP status predicts a differential response to colchicine. As a pilot study, it also aims to provide detailed data supporting design of further trial, such as sample size calculating, endpoint optimizing, etc.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
This is a single-center, prospective, randomized, open-label, assessor-blinded pilot trial. A total of 120 patients will be enrolled and stratified by CHIP variant status into a TET2-CHIP group or a non-CHIP group. TET2-CHIP group (N = 60): Participants will be randomized (1:1) to colchicine 0.5 mg once daily plus SoC therapy (n = 30) or SoC therapy alone (control; n = 30). Non-CHIP group (N = 60): Participants will be randomized (1:1) to colchicine 0.5 mg once daily plus SoC therapy (n = 30) or SoC therapy alone (control; n = 30). SoC therapy includes but is not limited to appropriate lipid lowering, anti-platelet therapy, anti-hypertensive and beta blockers as defined by local guidelines. Patients should also be instructed to follow heart healthy (low fat) diet and regular exercise program. The index qualifying ACS must have occurred at least 30 days and no more than 90 days prior to randomization.
Baseline assessment for all participants will include coronary CT angiography (CCTA) using photon-counting detector CT (PCD-CT), inflammatory biomarkers testing and CHIP variant sequencing. After randomization, participants will have visits at Month 0, 1, 3, 6, 9, and 12. Repeat CCTA for the assessment of coronary plaque will occur during the Month 12 visit. The primary endpoint is the percent change in total plaque volume in non-culprit coronary lesion from baseline to Month 12, measured by CCTA. Secondary endpoints include the percent change in other plaques (calcified plaque, noncalcified plaque, low attenuation plaque, and fibrotic plaque) volume of coronary artery plaque from baseline to Month 12; change in levels of inflammatory biomarkers (IL-6, IL-1β, IL-18, hs-CRP, and S100A12); change in the TET2-CHIP variant allele fraction; and major adverse cardiovascular events (MACE), defined as a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and ischemia-driven revascularization. Participants will be followed for 12 months.
Studietype
Inschrijving (Geschat)
Fase
- Fase 4
Contacten en locaties
Studiecontact
- Naam: Zaixin Jiang, MD, PhD
- Telefoonnummer: +8618646330195
- E-mail: jzxdr2013@163.com
Studie Locaties
-
-
Liaoning
-
Shenyang, Liaoning, China
- Werving
- General Hospital of Northern Theater Command
-
Hoofdonderzoeker:
- Yaling Han, MD, PhD
-
Contact:
- Zaixin Jiang, MD, PhD
- Telefoonnummer: +8618646330195
- E-mail: jzxdr2013@163.com
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
-
Age 40-85 years;
-
Patients with recent hospitalization for documented ACS (the index event occurring 30-90 days before randomization) and meeting all of the following:
- During the index hospitalization, patients underwent either PCI or diagnostic coronary angiography alone,
- At least one non-culprit coronary lesion with 30%-70% diameter stenosis by visual estimation on coronary angiography,
- Clinically stable throughout the screening period,
- Receiving standard of care therapy for ACS in accordance with national guidelines,
- Peripheral blood DNA available for targeted sequencing, with results demonstrating either TET2-CHIP or no CHIP-associated variants;
-
Written informed consent.
Exclusion Criteria:
- Prior coronary artery bypass grafting (CABG) before documented ACS;
- Other clinically significant cardiovascular diseases, including moderate-to-severe valvular heart disease (moderate or severe), heart failure (NYHA class III-IV), or atrial fibrillation;
- Non-culprit coronary anatomy (e.g., marked tortuosity, bifurcation lesions, or small vessels <1.5 mm in diameter) deemed to preclude plaque assessment by CCTA;
- Planned PCI or CABG;
- Abnormal liver function (ALT >3 times the upper limit of normal range) at randomization;
- Abnormal renal function (serum creatinine >1.5 times the upper limit of normal range or estimated eGFR <45 mL/min/1.73 m²) at randomization;
- Hematologic abnormalities: anemia (hemoglobin <100g/L), thrombocytopenia (platelet count <100×109/L) or leukopenia (white blood cell <3×109/L) at randomization;
- Inflammatory bowel disease (Crohn's or ulcerative colitis) or active diarrhea;
- Symptomatic peripheral neuropathy, pre-existing progressive neuromuscular disease or creatine kinase (CK) level > 3 times the upper limit of normal range as measured within the past 30 days and determined to be non-transient through repeat testing;
- Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception;
- Any contraindication, known allergy or intolerance to colchicine;
- Colchicine use within 30 days prior to randomization, or planned colchicine therapy for other indications;
- Current or planned use of any of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics;
- Existing or planned treatment with other anti-inflammatory or immunosuppressive drugs;
- History of malignancy (hematologic or solid-tumor);
- History of transplantation (hematopoietic stem cell or solid-organ);
- Significant radiation exposure (≥40 mSv) within the past 12 months;
- Known hypersensitivity to iodinated contrast media or uncontrolled active hyperthyroidism;
- Current enrollment in another clinical trial;
- A predicted life expectancy < 1 year;
- Any other circumstances in which the investigator judges that the patient is not suitable to participate in the clinical trial.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Enkel
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Colchicine with SoC therapy (TET2-CHIP group)
Participants with TET2-CHIP will receive colchicine 0.5 mg orally once daily plus standard of care (SoC) therapy for 12 months. |
SoC therapy includes but is not limited to appropriate lipid lowering, anti-platelet therapy, anti-hypertensive and beta blockers as defined by local guidelines. SoC therapy |
|
Geen tussenkomst: SoC therapy alone (TET2-CHIP group)
Participants with TET2-CHIP will receive SoC therapy alone (no colchicine) for 12 months. |
|
|
Experimenteel: Colchicine with SoC therapy (non-CHIP group)
Participants without CHIP-associated variants will receive colchicine 0.5 mg orally once daily plus standard of care (SoC) therapy for 12 months. |
SoC therapy includes but is not limited to appropriate lipid lowering, anti-platelet therapy, anti-hypertensive and beta blockers as defined by local guidelines. SoC therapy |
|
Geen tussenkomst: SoC therapy alone (non-CHIP group)
Participants without CHIP-associated variants will receive SoC therapy alone (no colchicine) for 12 months. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Percent change in total plaque volume of coronary artery plaque
Tijdsspanne: Up to 12 months
|
Percent change in total plaque volume of coronary artery plaque measured by CCTA |
Up to 12 months
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Percent change in other plaques (calcified plaque, noncalcified plaque, low attenuation plaque, and fibrotic plaque) volume of coronary artery plaque
Tijdsspanne: Up to 12 months
|
Percent change in other plaques (calcified plaque, noncalcified plaque, low attenuation plaque, and fibrotic plaque) volume of coronary artery plaque measured by CCTA. |
Up to 12 months
|
|
Change in levels of inflammatory biomarkers
Tijdsspanne: Up to 12 months
|
Change in levels of circulating IL-6, IL-1β, IL-18, hs-CRP, and S100A12. |
Up to 12 months
|
|
Change in TET2-CHIP variant allele fraction at 6 months
Tijdsspanne: Up to 6 months
|
Change in TET2-CHIP variant allele fraction measured by next generation sequencing. |
Up to 6 months
|
|
Change in TET2-CHIP variant allele fraction at 12 months
Tijdsspanne: Up to 12months
|
Change in TET2-CHIP variant allele fraction measured by next generation sequencing. |
Up to 12months
|
|
Major adverse cardiovascular events (MACE)
Tijdsspanne: Up to 12 months
|
A composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and ischemia-driven revascularization. |
Up to 12 months
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie stoel: Yaling Han, MD, PhD, The General Hospital of Northern Theater Command
Studie record data
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Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
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Eerst geplaatst (Werkelijk)
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Meer informatie
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Aanvullende relevante MeSH-voorwaarden
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