Anti-inflammatory Effects of Colchicine in PCI
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Intervention: Colchicine; Placebo
Intervention description: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later; Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
Intervention MeSH terms: Colchicine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 280.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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)
    

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