The Role of Colchicine in Reducing The Rate of Myocardial Reperfusion Injury

Reperfusion Injury, Myocardial Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05734612
• Other study ID #: 22-09-1046
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: December 4, 2022
• Est. completion date: March 31, 2023

Study information

• Verified date: February 2023
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Myocardial Reperfusion Injury
• Reperfusion Injury
• Reperfusion Injury, Myocardial
• Wounds and Injuries

Intervention

Drug:
• Colchicine
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.
• Placebo (lactose)
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.

Locations

Country	Name	City	State
Indonesia	Fakultas Kedokteran Universitas Indonesia	Jakarta Pusat	Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

References & Publications (8)

Akodad M, Lattuca B, Nagot N, Georgescu V, Buisson M, Cristol JP, Leclercq F, Macia JC, Gervasoni R, Cung TT, Cade S, Cransac F, Labour J, Dupuy AM, Roubille F. COLIN trial: Value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response. Arch Cardiovasc Dis. 2017 Jun-Jul;110(6-7):395-402. doi: 10.1016/j.acvd.2016.10.004. Epub 2017 Jan 3. — View Citation

Deftereos S, Giannopoulos G, Angelidis C, Alexopoulos N, Filippatos G, Papoutsidakis N, Sianos G, Goudevenos J, Alexopoulos D, Pyrgakis V, Cleman MW, Manolis AS, Tousoulis D, Lekakis J. Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study. Circulation. 2015 Oct 13;132(15):1395-403. doi: 10.1161/CIRCULATIONAHA.115.017611. Epub 2015 Aug 11. — View 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):e — View Citation

Mewton N, Roubille F, Bresson D, Prieur C, Bouleti C, Bochaton T, Ivanes F, Dubreuil O, Biere L, Hayek A, Derimay F, Akodad M, Alos B, Haider L, El Jonhy N, Daw R, De Bourguignon C, Dhelens C, Finet G, Bonnefoy-Cudraz E, Bidaux G, Boutitie F, Maucort-Boulch D, Croisille P, Rioufol G, Prunier F, Angoulvant D. Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction. Circulation. 2021 Sep 14;144(11):859-869. doi: 10.1161/CIRCULATIONAHA.121.056177. Epub 2021 Aug 23. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Rate of Myocardial Reperfusion Injury	The rate of hypotension, acute heart failure, arrhythmias, persistent chest pain, or microvascular obstruction up to 3 days after primary percutaneous coronary intervention after primary percutaneous coronary intervention	Up to 3 days after primary percutaneous coronary intervention
Secondary	Activation of NLRP3 in peripheral blood vein measured in counts	Activation of NLRP3 in peripheral blood vein 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention measured in counts	30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention
Secondary	Concentration of ASC in peripheral blood vein in ng/ml	Concentration of ASC in peripheral blood vein 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention in ng/ml	30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention
Secondary	Concentration of caspase in peripheral blood vein in pg/ml	Concentration of caspase in peripheral blood vein 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention in pg/ml	30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention
Secondary	Concentration of troponin in peripheral blood vein in ng/L	Concentration of troponin in peripheral blood vein 30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention in ng/L	30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention