Effect of Colchicine on MMP-9, NOX2, and TGF-β1 in Myocardial Infarct

NCT ID: NCT05709509

Last Updated: 2023-04-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2023-05-01

Brief Summary

Reducing NOX-2, MMP-9, and TGF-β1 Expression in Preventing Ventricular Remodelling Post Acute ST-Segment Elevation Myocardial Infarction using Colchicine (Post Late Reperfusion Percutaneous Coronary Intervention and Non-Reperfusion and In Vitro Study on Ischemic Rat Cardiomyocyte Culture Model). Coronary heart disease (CHD) is the most common cause of mortality and disability worldwide. The handling of reperfusion in Indonesia is still far below the required standard. Most STEMI patients in Indonesia arrive late to a health facility with symptoms that have been present for more than 12 hours (late-onset). Heart failure following a myocardial infarction is one of the long-term complications of STEMI. Patients with STEMU who do not receive reperfusion were more likely to develop this consequence. According to several studies, microtubules in cardiomyocytes have been identified as an essential regulator of cardiomyocytes' ability to respond to shear stress, which offers compression resistance and facilitates mitochondrial energy production. Microtubule densification, which occurs due to remodelling in heart failure, disrupts the microtubule network. The role of reactive oxygen species (ROS) produced by ischemic myocardium in this remodelling is thus inextricably linked. NADPH oxidase is one of the enzymes involved (NOX). NOX-2 levels have been reported to be higher in myocardial infarction and cardiac remodelling, and it has a close interaction with microtubule network, with damage of microtubule tissue increasing NOX-2 generation of reactive oxygen species. By eroding the ECM and triggering cytokines and chemokines to recruit inflammatory cells to eliminate necrotic cardiomyocytes, matrix metalloproteinase 9 (MMP-9) aids tissue rebuilding. Induction and activation of endogenous TGF-signaling pathways after myocardial infarction have also been discovered to play a function. TGF-β may play a role in the resolution of the inflammatory response in the early stages of infarct repair by inactivating macrophages and decreasing endothelial cell chemokine and cytokine production. TGF-β stimulates the fibrogenic pathway by causing extracellular matrix deposition and fibrosis later. Colchicine is a commonly prescribed anti-inflammatory medication with a low cost. the mechanism of colchicine is tubulin binding, which prevents microtubule assembly and polymerization. Colchicine inhibits microtubule development at low concentrations and promotes microtubule depolymerization at higher concentrations. Several studies have demonstrated that low-dose colchicine can help reduce severe cardiac outcomes such as cardiovascular mortality, stroke, and cardiac arrest following myocardial infarction. Colchicine is known to cause partial restoration of microtubule tissue in the perinuclear region. Colchicine has also been shown in earlier research to reduce the expression of MMP-9, NOX2, and TGF-β This study aims to evaluate whether colchicine could prevent ventricular remodelling in STEMI patients with delayed reperfusion and non reperfusion. The minor hypothesis of this study was colchicine can lower NOX-2, MMP-9, and TGF-β expression in the clinical situation of patients with delayed and non-reperfusion STEMI following PCI. Randomization with 1:1 allocation were used to classify the patients, each group include 41 patients with one group receiving colchicine therapy and standard therapy and the other receiving standard therapy only. Colchicine administration was the independent variable. STEMI patients with delayed and non-reperfusion IKP who met the inclusion criteria are included in this randomized clinical trial. Left ventricular end-diastolic volume (LVEDV) was the dependent variable while serum MMP-9, NOX-2, and TGF-β were the intermediate variables. In the treatment group, colchicine 1 mg is administered before PCI or admission to the ICCU, and colchicine is continued at 0.5 mg/day for a month. Within 24 to 36 hours of treatment initiation, the patient had echocardiography, NOX-2, MMP-9, and TGF-β levels evaluated. On days 4-5, a second NOX-2, MMP-9, and TGF-β screening were performed. The follow up two months after treatment initiation includes an assessment of drug compliance, symptoms, and echocardiography. Depending on the normality of the data distribution, the difference between groups is performed using the unpaired T-test or the Mann-Whitney test. The significant difference between the treatment groups is indicated by a p-value of 0.05.

Conditions

ST Elevation Myocardial Infarction; Colchicine; Cardiac Remodeling, Ventricular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Late PCI + Colchicine

Subjects that undergo late PCI (12-48 hours after STEMI), received optimal medical treatment (statin, aspirin, P2Y12 inhibitor, and nitrate), and colchicine

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. commonly used as anti-inflammatory drugs.

Percutaneous Coronary Intervention

Intervention Type: PROCEDURE

Percutaneous Coronary Intervention: a family of minimally invasive procedures used to open clogged coronary arteries (those that deliver blood to the heart)

Optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Intervention Type: OTHER

The subjects just received optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Late PCI + Optimal Medical Treatment

Subjects that undergo late PCI (12-48 hours after STEMI) and received optimal medical treatment (statin, aspirin, P2Y12 inhibitor, and nitrate)

Group Type: EXPERIMENTAL

Percutaneous Coronary Intervention

Intervention Type: PROCEDURE

Percutaneous Coronary Intervention: a family of minimally invasive procedures used to open clogged coronary arteries (those that deliver blood to the heart)

Optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Intervention Type: OTHER

The subjects just received optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Optimal Medical Treatment + Colchicine

Subjects that received optimal medical treatment (statin, aspirin, P2Y12 inhibitor, and nitrate) and colchicine

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. commonly used as anti-inflammatory drugs.

Optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Intervention Type: OTHER

The subjects just received optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Optimal Medical Treatment

Subjects that received optimal medical treatment (statin, aspirin, P2Y12 inhibitor, and nitrate)

Group Type: PLACEBO_COMPARATOR

Optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Intervention Type: OTHER

The subjects just received optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Interventions

Colchicine

Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. commonly used as anti-inflammatory drugs.

Intervention Type: DRUG

Percutaneous Coronary Intervention

Percutaneous Coronary Intervention: a family of minimally invasive procedures used to open clogged coronary arteries (those that deliver blood to the heart)

Intervention Type: PROCEDURE

Optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

The subjects just received optimal medical treatment including statin, aspirin, P2Y12 inhibitor, and nitrate.

Intervention Type: OTHER

Other Intervention Names

No Intervention

Eligibility Criteria

Inclusion Criteria

• Subjects who presenting with STEMI more than 12 hours from the onset of chest pain
• Aged 40-70 years
• Agreed with the informed consent

Exclusion Criteria

• aged <40 or >70 years
• subjects that have unstable condition such as comorbid disease (infection, inflammation, malignancy, severe renal failure (EGFR <30), a history of hepatic cirrhosis, acute exacerbation of hepatitis, or severe liver disease, alcoholic patient, cardiac arrest, ventricular fibrillation or cardiogenic shock, unstable hemodynamic)
• subjects that have colchicine hypersensitivity
• pregnancy or breastfeed

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitas Jember

UNKNOWN

Sponsor Role: collaborator

University of Brawijaya

OTHER

Sponsor Role: collaborator

RSD dr. Soebandi

OTHER_GOV

Sponsor Role: lead

Responsible Party

Suryono Suryono

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

RSD dr Soebandi

Jember, East Java, Indonesia

Site Status: RECRUITING

Countries

Indonesia

Central Contacts

Suryono Suryono, MD (Cardiologist)

Role: CONTACT

suryonofiha@gmail.com

+628123514186

Facility Contacts

Suryono Suryono, MD (Cardiologist)

Role: primary

suryonofiha@gmail.com

+628123514186

Other Identifiers

colchicine and Cardiovascular

Identifier Type: -

Identifier Source: org_study_id