Clinical trial NCT01709981: Anti-inflammatory Effects of Colchicine in PCI
Official title: Anti-inflammatory Effects of Colchicine in Patients Undergoing Percutaneous Coronary Intervention: Inflammatory Marker Substudy of the Colchicine-PCI Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2012-10-18
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: Percent Change in Post-procedural IL-6 Concentration From Baseline to 30 Min -1 hr After PCI
timeFrame: 30 minutes to 1 hour after PCI
Secondary outcomes:
measure: Percent Change in Post-procedural IL-6 Concentration From Baseline to 22-24 hr After PCI
timeFrame: baseline to 22-24 hr after PCI
measure: Percent Change in Post-procedural hsCRP Concentration From Baseline to 22-24 hr After PCI
timeFrame: baseline to 22-24 hr after PCI
measure: Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI
timeFrame: 30 minutes to 1 hour after PCI
measure: Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI
timeFrame: baseline to 22-24 hr after PCI
Other outcomes:
Locations:
city: New York
country: United States
facility: Manhattan VA Hospital
state: New York
city: New York
country: United States
facility: Bellevue Hospital Center
state: New York
city: New York
country: United States
facility: New York Langone Medical Center
state: New York
Study officials:
affiliation: NYU Langone Health
name: Binita Shah, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.