Oral Colchicine in Argentina to Prevent Restenosis (ORCA)

Centro de estudios en Cardiologia Intervencionista

Status and phase: Unknown; Phase 4

Conditions: Coronary Artery Disease; Acute Coronary Syndrome; Restenosis of Coronary Artery Stent; Atherosclerosis

Treatments: Drug: Colchicine

Study type: Interventional

Funder types: Other

Identifiers

NCT04382443

CECI-03

Details and patient eligibility

About

The Oral treatment of Colchicine in Argentina (ORCA) trial is a prospective, randomized, multicenter trial to included 450 patients with indication for myocardial revascularization with PCI between a group to be treated with BMS plus oral colchicine (OC) for three months, which should be administered at the time of PCI, these patients they would receive 0.5 mg twice a day per 3 months compared to the other group of patients who will be treated exclusively with last generation of DES.

Full description

In a previous randomized comparison oral colchicine plus bare metal stent (BMS) compared to BMS plus placebo in a diabetic High risk for re-stenosis population, OC demonstrate a significant reduction of angiographic and intravascular ultrasound parameters of in-stent restenosis (ISR) after BMS implantation at one year of follow up (Journal of the American College of Cardiology,2013,61,1678-1685), with a clinical indication of target lesion revascularization in 3.6%. In addition previous reported registries from our group with Drug Eluting Stents showed similar amount of reduction in clinical parameters (not angiographic) of restenosis (ERACI III trial, one year TVR in 8.8% with 1st DES design, Rodriguez A et al EuroIntervention 2006,2:53-60 and 4.0% with 2nd generation DES design ERACI IV Cardiac and cardiovascular interventions Journal, 2014 ). Taking in account those numbers the investigators sought to compare differences in overall cost with both revascularization strategies at 1, 2, 3 and 5 years of follow up assuming that safety and efficacy clinical end points would be similar. Cost included in hospital, procedural and resources fees, follow up cost including re-hospitalization driving by target vessel revascularization (TVR) and both spontaneous and TVR myocardial infarction (MI) and medication cost for each revascularization strategies Safety end point will be incidence of major adverse cardiac events (MACE) defined as the composite of death from any cause, MI (peri-procedural and spontaneous at follow up) and ischemic driving TVR.

The study will be considered complete after all subjects have completed the 12-month Primary safety and efficacy endpoint was incidence of target vessel failure (TVF) plus one year overall cost with both strategies.. Additional end points are clinical endpoints measured in-hospital at at follow up period. cardiac death, cardiac death plus MI. spontaneous MI beyond 30 day to 5 years, and stent thrombosis rate (ST) (definite or probable by Academic Research Consortium definitions).

A sub-study of changes in biological markers of inflammation in patients with acute coronary syndrome (ACS) including MI will be analyzed in both groups. For this reason, a measurement of interleukin 6, metalloproteases, adiponectin and Protein C reactive (PCR) will be performed at the time of enrolment and 4 days and a month after inclusion.

Enrollment: 450 estimated patients

Sex: All

Ages: 18 to 110 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinical and angiographic

  1. Subject must be at least 18 to 80 years of age.

  2. Subject (or legal guardian) indicates understanding of the trial requirements and the treatment procedures and provides written informed consent before procedures are performed.

  3. Subject is eligible for PCI

  4. Subject has symptomatic coronary artery disease or silent ischemia with objective evidence of ischemia, or acute coronary syndromes, and qualifies for PCI

  5. Subject has a left ventricular ejection fraction (LVEF) > 40 % as measured within 60 days prior to enrollment.

  6. Subject is willing to comply with all protocol-required follow-up evaluations.

  7. Subject has one or more coronary artery stenosis of ≥ 70 % in a coronary artery with visually estimated reference vessel diameter (RVD) ≥2.50 mm.

Exclusion criteria

Clinical and angiographic

1. Subject has a known allergy to contrast (that cannot be adequately pre-medicated) and/or the stent system or Colchicine. (e.g., cobalt chromium alloy, stainless steel, all P2Y12 inhibitors, or aspirin)

2. Planned surgery within 30 days after the index procedure

3. Other serious medical illness (e.g., cancer, congestive heart failure) with estimated life expectancy of less than 36 months.

4. Current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.)

5. Planned procedure that may cause non-compliance with the protocol or confound data interpretation.

6. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions

7. Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint, or that, in the opinion of the investigator, may cause non-compliance with the protocol or confound data interpretation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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450 participants in 2 patient groups

Oral Colchicine +BMS implantation

Experimental group

Description:

This group will receive after BMS and Colchicine, at the time of PCI, 0,5 mg twice a day during the first three months after stent implantation

Treatment:

Drug: Colchicine

Second generation Drug eluting stent (DES)

No Intervention group

Description:

This group will receive DES at the moment of randomization and will be treated as standard of care. All second generation DES should be approved by ANMAT for clinical use.