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

• Sponsor: Indonesia University (Other)
• Overall Status: Enrolling by invitation
• CT.gov ID: NCT05734612
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 3.8
• Patients Per Site Per Month: 20.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Reperfusion Injury, Myocardial	Drug: Colchicine; Drug: Placebo (lactose)	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Colchicine and placebo (lactose) will be packed in capsules with the same appearance by the pharmacist. The pharmacist will code the capsules containing colchicine or the capsules containing placebo into group A or group B without informing the participant, care provider, investigator, and outcome assessor regarding the content of each group of capsules. Participant, care provider, investigator, and outcome assessor do not know the content of the capsules given to the participants.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 4, 2022
• Anticipated Primary Completion Date: Mar 31, 2023
• Anticipated Study Completion Date: Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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 Comparator: Placebo 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.	Drug: 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.

Outcome Measures

Primary Outcome Measures

1. The Rate of Myocardial Reperfusion Injury [Up to 3 days after primary percutaneous coronary intervention]

   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

Secondary Outcome Measures

1. Activation of NLRP3 in peripheral blood vein measured in counts [30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention]

   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

2. Concentration of ASC in peripheral blood vein in ng/ml [30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention]

   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

3. Concentration of caspase in peripheral blood vein in pg/ml [30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention]

   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

4. Concentration of troponin in peripheral blood vein in ng/L [30 minutes before, 30 minutes after, 24 hours after, and 48 hours after primary percutaneous coronary intervention]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fakultas Kedokteran Universitas Indonesia	Jakarta Pusat	Jakarta	Indonesia	10430

Sponsors and Collaborators

• Indonesia University

Investigators

• Principal Investigator: Birry Karim, Fakultas Kedokteran Universitas Indonesia

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: dr. Birry Karim, SpPD-KKV, dr. Birry Karim, SpPD-KKV, Indonesia University
• ClinicalTrials.gov Identifier: NCT05734612
• Other Study ID Numbers: 22-09-1046
• First Posted: Feb 21, 2023
• Last Update Posted: Feb 21, 2023
• Last Verified: Feb 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by dr. Birry Karim, SpPD-KKV, dr. Birry Karim, SpPD-KKV, Indonesia University: Myocardial reperfusion injury; Colchicine
• Additional relevant MeSH terms: Reperfusion Injury; Myocardial Reperfusion Injury; Wounds and Injuries; Colchicine

Study Results

No Results Posted as of Feb 21, 2023