Anti-inflammatory Effects of Colchicine in PCI

Anti-inflammatory Effects of Colchicine in Patients Undergoing Percutaneous Coronary Intervention: Inflammatory Marker Substudy of the Colchicine-PCI Trial

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)

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Colchicine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Bellevue Hospital Center
    • New York, New York, United States, 10016
      • New York Langone Medical Center
    • New York, New York, United States, 10010
      • Manhattan VA Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; 1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later	Drug: Colchicine; Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later; Other Names: Colcrys
Placebo Comparator: Placebo; Placebo 1-2 hours prior PCI, followed by placebo 1 hour later	Drug: Placebo; Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change in Post-procedural IL-6 Concentration From Baseline to 30 Min -1 hr After PCI	30 minutes to 1 hour after PCI

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change in Post-procedural IL-6 Concentration From Baseline to 22-24 hr After PCI	baseline to 22-24 hr after PCI
Percent Change in Post-procedural hsCRP Concentration From Baseline to 22-24 hr After PCI	baseline to 22-24 hr after PCI
Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI	30 minutes to 1 hour after PCI
Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI	baseline to 22-24 hr after PCI

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Takeda
• Investigators: Principal Investigator: Binita Shah, MD, NYU Langone Health

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2013
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): December 13, 2021

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 11-02573