Anti-inflammatory Effects of Colchicine in PCI
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Purpose
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 and rates of peri-procedural myonecrosis and MI.
| Condition | Intervention | Phase |
|---|---|---|
|
Coronary Artery Disease |
Drug: Colchicine Drug: Placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Anti-inflammatory Effects of Colchicine in Patients Undergoing Percutaneous Coronary Intervention |
- Post-procedural IL-6 level [ Time Frame: 30 minutes to 1 hour after PCI ] [ Designated as safety issue: No ]
- Other relevant inflammatory markers [ Time Frame: 30 minutes to 1 hour, 6 to 8 hours, and ~24 hours (next day morning collection) post-PCI ] [ Designated as safety issue: No ]cell-associated L- selectin, cell-associated beta-2 integrin, interleukin-1 receptor antagonist, soluble E- selectin, intercellular cell adhesion molecule-1, pentraxin 3, CCL-21, CXCL-16, tumor necrosis factor-α, white blood cell count, and neutrophil count
- 30-day MACE [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]all-cause mortality, non-fatal MI, and target vessel revascularizaiton
- post-procedural myonecrosis [ Time Frame: 6 to 8 hours and 12 to 16 hours post-PCI ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 400 |
| Study Start Date: | December 2012 |
| Estimated Study Completion Date: | January 2016 |
| Estimated Primary Completion Date: | December 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 Name: 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
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Contact: Steven P Sedlis, MD | 2129513335 | steven.sedlis@nyumc.org |
| Contact: Binita Shah, MD, MS | 2122635656 | binita.shah@nyumc.org |
| United States, New York | |
| New York Langone Medical Center | Not yet recruiting |
| New York, New York, United States, 10016 | |
| Contact: Steven P. Sedlis, MD 212-951-3335 steven.sedlis@nyumc.org | |
| Contact: Binita Shah, MD, MS 2122635656 binita.shah@nyumc.org | |
| Bellevue Hospital Center | Not yet recruiting |
| New York, New York, United States, 10016 | |
| Contact: Steven P Sedlis, MD 212-951-3335 steven.sedlis@nyumc.org | |
| Contact: Binita Shah, MD, MS 2122635656 binita.shah@nyumc.org | |
| Principal Investigator: | Steven P Sedlis, MD | New York University School of Medicine |
| Principal Investigator: | Binita Shah, MD, MS | New York University School of Medicine |
More Information
No publications provided
| Responsible Party: | Steven Sedlis, Associate Professor of Medicine, New York University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT01709981 History of Changes |
| Other Study ID Numbers: | 11-02573 |
| Study First Received: | October 16, 2012 |
| Last Updated: | April 12, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: New York University School of Medicine Institutional Review Board (Board C) |
Additional relevant MeSH terms:
|
Coronary Artery Disease Myocardial Ischemia Coronary Disease Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Anti-Inflammatory Agents Colchicine |
Therapeutic Uses Pharmacologic Actions Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Gout Suppressants Antirheumatic Agents Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 16, 2013