Anti-inflammatory Effects of Colchicine in PCI

NCT ID: NCT01709981

Last Updated: 2022-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-30
• Study Completion Date: 2021-12-13

Brief Summary

Peri-procedural inflammation is associated with increased rates of post-procedural myocardial infarction (MI), which occur in up to 35% of PCI patients and are themselves associated with increased risk of later MI and death. Statins suppress both inflammatory markers and MI rates during and after PCI, but ≥ 40% of PCI patients go statin-untreated, due in part to side effects such as myalgia. Moreover, because their mechanism of action relies on post-translational effects, statins must be given ≥ 12 to 24 hours prior to PCI, a time frame that is not always feasible. The investigators propose a novel alternative approach to reduce inflammation during PCI employing colchicine, an anti-inflammatory medication used frequently in gout and pericarditis. Colchicine may be particularly applicable to the PCI setting due to its rapid onset of action and excellent side-effect profile at low doses, as well as its known mechanisms of action. However, data on colchicine use in patients with coronary disease is extremely limited, and no studies to date have evaluated the use of colchicine in patients undergoing PCI. The investigators aim to characterize a potential mechanism of benefit in patients undergoing PCI by evaluating the effects of colchicine on soluble and leukocyte surface markers after PCI. The investigators also aim to determine the effects of colchicine on peri-procedural myonecrosis and MI. Accordingly, the investigators propose a prospective randomized study to characterize the effect of colchicine on inflammation and peri-procedural myocnecrosis. Patients referred for possible PCI will be randomized in a double-blinded fashion to placebo or colchicine (1.2mg 1 to 2 hours before PCI, followed by 0.6mg 1 hour later). The primary endpoint will be post-procedural interleukin-6 level. Secondary endpoints will include other relevant soluble and leukocyte-associated inflammatory markers. Sample size needed is 200 patients undergoing PCI. To adjust for a floor effect, 280 patients undergoing PCI will be needed. 400 patients will likely be needed to be enrolled to reach 280 PCIs (the remaining will have undergone a diagnostic only procedure). Of note, this is a substudy of the COLCHICINE-PCI trial (NCT 02594111)

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Colchicine

1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later

Placebo

Placebo 1-2 hours prior PCI, followed by placebo 1 hour later

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later

Interventions

Colchicine

Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later

Intervention Type: DRUG

Placebo

Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later

Intervention Type: DRUG

Other Intervention Names

Colcrys

Eligibility Criteria

Inclusion Criteria

• Patients must be more than 18 years of age and referred for coronary angiography

Exclusion Criteria

• Plan for diagnostic-only coronary angiography
• On colchicine chronically
• History of intolerance to colchicine
• Glomerular filtration rate <30mL/minute or on dialysis
• Active malignancy or infection
• History of myelodysplasia
• High-dose statin load <24 hours prior to procedure
• Use of oral steroids or non-steroidal anti-inflammatory agents other than aspirin within 72 hours or 3 times the agent's half-life (whichever is longer)
• Use of strong CYP3A4/P-glycoprotein inhibitors (specifically ritonavir, ketoconazole, clarithromycin, cyclosporine, diltiazem and verapamil)
• Unable to consent
• Participating in a competing study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Binita Shah, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

Manhattan VA Hospital

New York, New York, United States

Bellevue Hospital Center

New York, New York, United States

New York Langone Medical Center

New York, New York, United States

Countries

United States

References

Shah B, Pillinger M, Zhong H, Cronstein B, Xia Y, Lorin JD, Smilowitz NR, Feit F, Ratnapala N, Keller NM, Katz SD. Effects of Acute Colchicine Administration Prior to Percutaneous Coronary Intervention: COLCHICINE-PCI Randomized Trial. Circ Cardiovasc Interv. 2020 Apr;13(4):e008717. doi: 10.1161/CIRCINTERVENTIONS.119.008717. Epub 2020 Apr 16.

Reference Type: DERIVED

PMID: 32295417 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

11-02573

Identifier Type: -

Identifier Source: org_study_id