- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT07362966
Kolkisiinin vaikutus sepelvaltimoiden ateroskleroosin etenemiseen potilailla, joilla on TET2-CHIP-variantti
Kolkisiinin vaikutus sepelvaltimoiden ateroskleroosin etenemiseen potilailla, joilla on TET2-CHIP-variantti: pilottikliininen tutkimus (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.
Tutkimuksen yleiskatsaus
Tila
Ehdot
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 4
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: Zaixin Jiang, MD, PhD
- Puhelinnumero: +8618646330195
- Sähköposti: jzxdr2013@163.com
Opiskelupaikat
-
-
Liaoning
-
Shenyang, Liaoning, Kiina
- Rekrytointi
- General Hospital of Northern Theater Command
-
Päätutkija:
- Yaling Han, MD, PhD
-
Ottaa yhteyttä:
- Zaixin Jiang, MD, PhD
- Puhelinnumero: +8618646330195
- Sähköposti: jzxdr2013@163.com
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Yksittäinen
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: 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 |
|
Ei väliintuloa: SoC therapy alone (TET2-CHIP group)
Participants with TET2-CHIP will receive SoC therapy alone (no colchicine) for 12 months. |
|
|
Kokeellinen: 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 |
|
Ei väliintuloa: SoC therapy alone (non-CHIP group)
Participants without CHIP-associated variants will receive SoC therapy alone (no colchicine) for 12 months. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Percent change in total plaque volume of coronary artery plaque
Aikaikkuna: Up to 12 months
|
Percent change in total plaque volume of coronary artery plaque measured by CCTA |
Up to 12 months
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Percent change in other plaques (calcified plaque, noncalcified plaque, low attenuation plaque, and fibrotic plaque) volume of coronary artery plaque
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Up to 12months
|
Change in TET2-CHIP variant allele fraction measured by next generation sequencing. |
Up to 12months
|
|
Major adverse cardiovascular events (MACE)
Aikaikkuna: Up to 12 months
|
A composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and ischemia-driven revascularization. |
Up to 12 months
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Opintojen puheenjohtaja: Yaling Han, MD, PhD, The General Hospital of Northern Theater Command
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- PRECISE
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .