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

NCT05734612 | Unknown Phase 3 DMC

• 1 other identifier: 22-09-1046
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Reperfusion Injury, Myocardial

Keywords

Myocardial reperfusion injury; Colchicine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• 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 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 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

Study Arms (2)

Colchicine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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)

Interventions

Colchicine DRUG

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.

Colchicine

Placebo (lactose) DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Fakultas Kedokteran Universitas Indonesia

Jakarta Pusat, Jakarta Special Capital Region, 10430, Indonesia

Location

Related Publications (8)

• 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.

  PMID: 26265659 BACKGROUND

• 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.

  PMID: 28065445 BACKGROUND

• 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.

  PMID: 34420373 BACKGROUND

• 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.

  PMID: 30185392 BACKGROUND

• 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.

  PMID: 21918905 BACKGROUND

• 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.

  PMID: 27129183 BACKGROUND

• 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.

  PMID: 29055633 BACKGROUND

• 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.

  PMID: 26304941 RESULT

MeSH Terms

Conditions

Myocardial Reperfusion Injury

Interventions

Colchicine; Lactose

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Reperfusion Injury; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Birry Karim

  Fakultas Kedokteran Universitas Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: dr. Birry Karim, SpPD-KKV

Model Details: 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.

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: February 21, 2023
• Study Start: December 4, 2022
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)