Clinical trial NCT05734612: The Role of Colchicine in Reducing The Rate of Myocardial Reperfusion Injury
Official title: The Role of Colchicine in Reducing The Rate of Myocardial Reperfusion Injury in Patients With ST-Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention: Study on NLRP3, ASC, Caspase, and Troponin
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Reperfusion Injury, Myocardial
Keywords: Myocardial reperfusion injury
Colchicine
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2023-02-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be grouped into two groups which are intervention group and control group. Patients in the intervention group receive loading dose of colchicine 1 x 2 mg followed by colchicine 2 x 0,5 mg daily for two consecutive days. Patients in the control group receive loading dose of placebo (lactose) 1 x 2 mg followed by lactose 2 x 0,5 mg daily for two consecutive days.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to investigate the role of colchicine in reducing the rate of myocardial reperfusion injury in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. The main questions it aims to answer are:

* Does colchicine reduce the rate of myocardial reperfusion injury ?
* Does colchicine reduce the concentration of markers of myocardial reperfusion injury (NLRP3, ASC, caspase, and troponin) ?

Participants will

* Be grouped into intervention group and control group blindly. Patients in the intervention group receive loading dose of colchicine 1 x 2 mg followed by colchicine 2 x 0,5 mg daily for two consecutive days. Patients in the control group receive loading dose of placebo (lactose) 1 x 2 mg followed by lactose 2 x 0,5 mg daily for two consecutive days.
* Undergo peripheral blood vein examination before primary percutaneous coronary intervention, after primary percutaneous coronary intervention, 24 hour after primary percutaneous coronary intervention, and 48 hour after primary percutaneous coronary intervention.

Researchers will compare intervention group and control group to see if colchicine reduces the rate of myocardial reperfusion injury and reduces the concentration of markers of myocardial reperfusion injury (NLRP3, ASC, caspase, and troponin) in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention.


Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with ST-elevation myocardial infarction based on clinical symptoms, signs, and electrocardiography who undergo primary percutaneous coronary intervention
* Patients aged 18 - 80 years old

Exclusion Criteria:

* Patients with malignancy
* Patients with allergic reaction to colchicine
* Stroke within the last 3 months
* Severe infection (sepsis)
* Chronic kidney disease with eGFR of \<30mL/min/1.73m2

Primary outcomes:
measure: The Rate of Myocardial Reperfusion Injury
timeFrame: Up to 3 days after primary percutaneous coronary intervention
Secondary outcomes:
measure: Activation of NLRP3 in peripheral blood vein measured in counts
timeFrame: 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention
measure: Concentration of ASC in peripheral blood vein in ng/ml
timeFrame: 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention
measure: Concentration of caspase in peripheral blood vein in pg/ml
timeFrame: 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention
measure: Concentration of troponin in peripheral blood vein in ng/L
timeFrame: 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Fakultas Kedokteran Universitas Indonesia
state: Jakarta
Study officials:
affiliation: Fakultas Kedokteran Universitas Indonesia
name: Birry Karim
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Vaidya K, Martinez G, Patel S. The Role of Colchicine in Acute Coronary Syndromes. Clin Ther. 2019 Jan;41(1):11-20. doi: 10.1016/j.clinthera.2018.07.023. Epub 2018 Sep 2.
citation: Raju NC, Yi Q, Nidorf M, Fagel ND, Hiralal R, Eikelboom JW. Effect of colchicine compared with placebo on high sensitivity C-reactive protein in patients with acute coronary syndrome or acute stroke: a pilot randomized controlled trial. J Thromb Thrombolysis. 2012 Jan;33(1):88-94. doi: 10.1007/s11239-011-0637-y.
citation: Robertson S, Martinez GJ, Payet CA, Barraclough JY, Celermajer DS, Bursill C, Patel S. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation. Clin Sci (Lond). 2016 Jul 1;130(14):1237-46. doi: 10.1042/CS20160090. Epub 2016 Apr 21.
citation: Vaidya K, Arnott C, Martinez GJ, Ng B, McCormack S, Sullivan DR, Celermajer DS, Patel S. Colchicine Therapy and Plaque Stabilization in Patients With Acute Coronary Syndrome: A CT Coronary Angiography Study. JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 2):305-316. doi: 10.1016/j.jcmg.2017.08.013. Epub 2017 Oct 18.
citation: Martinez GJ, Robertson S, Barraclough J, Xia Q, Mallat Z, Bursill C, Celermajer DS, Patel S. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome. J Am Heart Assoc. 2015 Aug 24;4(8):e002128. doi: 10.1161/JAHA.115.002128.