Anti-inflammatory Effects of Colchicine in PCI

NCT01709981 | Completed Phase 4 Results

• 1 other identifier: 11-02573
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 3

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)

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  30 minutes to 1 hour 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

Study Arms (2)

Colchicine

EXPERIMENTAL

1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

Placebo 1-2 hours prior PCI, followed by placebo 1 hour later

Drug: Placebo

Interventions

Colchicine DRUG

Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later

Also known as: Colcrys

Colchicine

Placebo DRUG

Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be more than 18 years of age and referred for coronary angiography

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• Takeda: collaborator

Study Sites (3)

Manhattan VA Hospital

New York, New York, 10010, United States

Location

Bellevue Hospital Center

New York, New York, 10016, United States

Location

New York Langone Medical Center

New York, New York, 10016, United States

Location

Related Publications (1)

• 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.

  PMID: 32295417 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Binita Shah
• Organization: NYU Langone Health

Binita.Shah@nyulangone.org

212-263-6631

Study Officials

• Binita Shah, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 18, 2012
• Study Start: May 30, 2013
• Primary Completion: August 30, 2019
• Study Completion: December 13, 2021
• Last Updated: May 25, 2022
• Results First Posted: September 9, 2020

Record last verified: 2022-05

Locations

US (3)