Clinical trial NCT06543082: MACT (Mono Antiplatelet and Colchicine Therapy) Prospective Multicenter Study
Official title: Clinical Outcomes of Colchicine Therapy Following Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: the MACT (Mono Antiplatelet and Colchicine Therapy) Prospective Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: Colchicine
Lead sponsor: CHA University
Sponsor class: OTHER
Collaborators: name: Biotronik SE & Co. KG
First posted: 2024-08-07
Enrollment: 490
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The previous Mono Antiplatelet and Colchicine Therapy (MACT) pilot study (NCT04949516) demonstrated that it was feasible to discontinue aspirin therapy and administer low-dose colchicine on the day after percutaneous coronary intervention (PCI) in addition to potent P2Y12 inhibitors in patients with acute coronary syndrome (ACS). However, the efficacy and safety of MACT have not yet been investigated. The goal of this clinical trial is to evaluate the clinical outcomes of ticagrelor P2Y12 inhibitor monotherapy combined with colchicine immediately after PCI in patients with ACS. The main questions it aims to answer are:

* What is the frequency of the composite endpoint of cardiovascular death, nonfatal spontaneous myocardial infarction, nonfatal ischemic stroke, unplanned hospitalization leading to urgent revascularization, and major bleeding at 12 months post-intervention?
* What is the frequency of stent thrombosis at 12 months post-intervention?

For pre-specified analyses, researchers will compare MACT to less than 1 month, 3-month, and 12-month dual antiplatelet therapy (individual patient data from the T-PASS \[NCT03797651\] and TICO \[NCT02494895\] trials) to determine if MACT is effective in treating ACS.

Participants will:

* Take low-dose colchicine in addition to ticagrelor maintenance therapy, discontinuing aspirin the day after PCI.
* Take a high-sensitivity C-reactive protein (hs-CRP) test 1 month after PCI.
* Discontinue colchicine if the hs-CRP level is less than 2 mg/L, or continue colchicine if it is not.
* Visit the clinic for check-ups at 1, 3, 6, 9, and 12 months after PCI.


Eligibility criteria: Inclusion Criteria:

* Participants with positive troponin acute coronary syndrome who have undergone implantation of ultrathin bioresorbable polymer sirolimus-eluting stents (Orsiro; Biotronik AG).
* Participants who have provided written informed consent.

Exclusion Criteria:

* Under 19 years of age.
* Stent treatment failure lesions (stent restenosis or thrombosis).
* Cardiac arrest or cardiogenic shock.
* Currently taking or requiring strong CYP3A4 inhibitors (atazanavir, clarithromycin, darunavir/ritonavir, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, tipranavir/ritonavir) or P-glycoprotein inhibitors (cyclosporine, ranolazine).
* Presence of any of the following concomitant conditions: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia, severe gastrointestinal diseases, or genetic disorders such as galactose intolerance.
* Hypersensitivity to colchicine treatment.
* Currently taking colchicine for another condition.
* Requiring anticoagulant therapy.
* Liver disease classified as Child-Pugh class B or C.
* Renal disease with creatinine clearance \<50 mL/min.
* Pregnant, breastfeeding, or women of childbearing age.
* Currently has a malignancy or has a history of malignancy within the past 5 years.
* Life expectancy of less than 5 years.
* Contraindication for ticagrelor use (history of intracranial hemorrhage, active pathological bleeding, or liver disease classified as Child-Pugh class B or C).

Primary outcomes:
measure: Efficacy Outcome: Net adverse clinical event
timeFrame: 12 months post-intervention
measure: Safety Outcome: Stent thrombosis
timeFrame: 12 months post-intervention
Secondary outcomes:
measure: Cardiovascular death
timeFrame: 12 months post-intervention
measure: Nonfatal spontaneous (nonprocedural) myocardial infarction
timeFrame: 12 months post-intervention
measure: Nonfatal ischemic stroke
timeFrame: 12 months post-intervention
measure: Unplanned hospitalization leading to urgent revascularization
timeFrame: 12 months post-intervention
measure: Major bleeding
timeFrame: 12 months post-intervention
measure: High residual inflammation
timeFrame: 1 month, 6 months, and 12 months post-intervention
measure: High residual platelet reactivity
timeFrame: 1 month and 12 months post-intervention
measure: Low residual platelet reactivity
timeFrame: 1 month and 12 months post-intervention
measure: Thrombogenicity
timeFrame: 1 month and 12 months post-intervention
measure: Adverse drug reaction to colchicine
timeFrame: 1 month, 3 months, 6 months, 9 months, and 12 months
Other outcomes:
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Gyeonggi-do
Study officials:
affiliation: CHA Bundang Medical Center
name: Seung-Yul Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee SY, Jeong YH, Yun KH, Cho JY, Gorog DA, Angiolillo DJ, Kim JW, Jang Y. P2Y12 Inhibitor Monotherapy Combined With Colchicine Following PCI in ACS Patients: The MACT Pilot Study. JACC Cardiovasc Interv. 2023 Aug 14;16(15):1845-1855. doi: 10.1016/j.jcin.2023.05.035.
citation: Lee SY, Cho JY, Gorog DA, Angiolillo DJ, Yun KH, Ahn JH, Koh JS, Park Y, Hwang SJ, Hwang JY, Kim JW, Jang Y, Jeong YH. Inflammation and platelet reactivity during adjunctive colchicine versus aspirin in patients with acute coronary syndrome treated with potent P2Y12 inhibitor. Front Med (Lausanne). 2024 Apr 19;11:1349577. doi: 10.3389/fmed.2024.1349577. eCollection 2024.
citation: Kim BK, Hong SJ, Cho YH, Yun KH, Kim YH, Suh Y, Cho JY, Her AY, Cho S, Jeon DW, Yoo SY, Cho DK, Hong BK, Kwon H, Ahn CM, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Hong MK, Jang Y; TICO Investigators. Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. JAMA. 2020 Jun 16;323(23):2407-2416. doi: 10.1001/jama.2020.7580.
citation: Hong SJ, Lee SJ, Suh Y, Yun KH, Kang TS, Shin S, Kwon SW, Lee JW, Cho DK, Park JK, Bae JW, Kang WC, Kim S, Lee YJ, Ahn CM, Kim JS, Kim BK, Ko YG, Choi D, Jang Y, Hong MK; T-PASS (Ticagrelor Monotherapy in Patients Treated With New-Generation Drug-Eluting Stents for Acute Coronary Syndrome) Investigators. Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial. Circulation. 2024 Feb 20;149(8):562-573. doi: 10.1161/CIRCULATIONAHA.123.066943. Epub 2023 Oct 25.
citation: Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007 May 1;115(17):2344-51. doi: 10.1161/CIRCULATIONAHA.106.685313.
citation: Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.