Anti-inflammatory Effects of Colchicine in PCI

Phase 4

Completed

• Conditions: Coronary Artery Disease
• Interventions: Drug: Colchicine; Drug: Placebo

• Registration Number: NCT01709981
• Lead Sponsor: NYU Langone Health

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-10-16
• Study First Submitted QC: 2012-10-17
• Study First Posted: 2012-10-18
• Study Start: 2013-05-30
• Primary Completion: 2019-08-30
• Results First Submitted: 2020-07-23
• Results First Submitted QC: 2020-08-26
• Results First Posted: 2020-09-09
• Study Completion: 2021-12-13
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-03
• Last Update Posted: 2022-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 280

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Colchicine	Colchicine	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later
Placebo	Placebo	Placebo 1-2 hours prior PCI, followed by placebo 1 hour later

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	baseline to 22-24 hr after PCI

Trial Locations

Locations (3)

Bellevue Hospital Center; 🇺🇸 New York, New York, United States

Manhattan VA Hospital; 🇺🇸 New York, New York, United States

New York Langone Medical Center; 🇺🇸 New York, New York, United States