Anti-inflammatory Effects of Colchicine in PCI

This study is currently recruiting participants.
Verified February 2014 by New York University School of Medicine
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Steven Sedlis, New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01709981
First received: October 16, 2012
Last updated: February 19, 2014
Last verified: February 2014
  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. Sample size needed is 200 patients undergoing PCI. 400 patients will likely be needed to be enrolled to reach 200 PCIs given that no more than 50% of patients enrolled may undergo diagnostic only procedure (without PCI).


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

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Post-procedural IL-6 level [ Time Frame: 30 minutes to 1 hour after PCI ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ~24 hours post-PCI ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: June 2013
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
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01709981

Contacts
Contact: Steven P Sedlis, MD 2129513335 steven.sedlis@nyumc.org
Contact: Binita Shah, MD, MS 2122635656 binita.shah@nyumc.org

Locations
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 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   
Sponsors and Collaborators
New York University School of Medicine
Takeda
Investigators
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: February 19, 2014
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 April 23, 2014