Anti-inflammatory Effects of Colchicine in PCI

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01709981
• Collaborator: Takeda (Industry)
• Enrollment: 280
• Locations: 3
• Arms: 2
• Actual Duration (Months): 102.5
• Patients Per Site: 93.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Colchicine; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Anti-inflammatory Effects of Colchicine in Patients Undergoing Percutaneous Coronary Intervention: Inflammatory Marker Substudy of the Colchicine-PCI Trial
• Actual Study Start Date: May 30, 2013
• Actual Primary Completion Date: Aug 30, 2019
• Actual Study Completion Date: Dec 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

1. Percent Change in Post-procedural IL-6 Concentration From Baseline to 22-24 hr After PCI [baseline to 22-24 hr after PCI]

2. Percent Change in Post-procedural hsCRP Concentration From Baseline to 22-24 hr After PCI [baseline to 22-24 hr after PCI]

3. Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI [30 minutes to 1 hour after PCI]

4. Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI [baseline to 22-24 hr after PCI]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• 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

Locations

	Site	City	State	Country	Postal Code
1	Manhattan VA Hospital	New York	New York	United States	10010
2	Bellevue Hospital Center	New York	New York	United States	10016
3	New York Langone Medical Center	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health
• Takeda

Investigators

• Principal Investigator: Binita Shah, MD, NYU Langone Health

Study Documents (Full-Text)

• Study Protocol - Aug 7, 2019
• Statistical Analysis Plan - Aug 7, 2019

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT01709981
• Other Study ID Numbers: 11-02573
• First Posted: Oct 18, 2012
• Last Update Posted: May 25, 2022
• Last Verified: May 1, 2022

• Additional relevant MeSH terms: Coronary Artery Disease; Colchicine

Study Results

Participant Flow

Arm/Group Title	Colchicine	Placebo
Arm/Group Description	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later Colchicine: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later	Placebo 1-2 hours prior PCI, followed by placebo 1 hour later Placebo: Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
Period Title: Overall Study
STARTED	141	139
COMPLETED	141	139
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Colchicine	Placebo	Total
Arm/Group Description	Colchicine	Placebo	Total of all reporting groups
Overall Participants	141	139	280
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.31 (9.29)	65.15 (10.38)	64.7 (9.8)
Sex: Female, Male (Count of Participants)
Female	11 7.8%	12 8.6%	23 8.2%
Male	130 92.2%	127 91.4%	257 91.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	34 24.1%	30 21.6%	64 22.9%
Not Hispanic or Latino	107 75.9%	109 78.4%	216 77.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 2.8%	11 7.9%	15 5.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	32 22.7%	25 18%	57 20.4%
White	105 74.5%	102 73.4%	207 73.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 0.7%	1 0.4%
Region of Enrollment (participants) [Number]
United States	141 100%	139 100%	280 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Post-procedural IL-6 Concentration From Baseline to 30 Min -1 hr After PCI
Time Frame	30 minutes to 1 hour after PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchicine	Placebo
Arm/Group Description	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later Colchicine: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later	Placebo 1-2 hours prior PCI, followed by placebo 1 hour later Placebo: Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
Measure Participants	140	138
Median (Inter-Quartile Range) [% change]	0	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Colchicine, Placebo
	Comments
	Type of Statistical Test	Equivalence
	Comments	Mann-Whitney
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	2-sided

2. Secondary Outcome

Title	Percent Change in Post-procedural IL-6 Concentration From Baseline to 22-24 hr After PCI
Time Frame	baseline to 22-24 hr after PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchicine	Placebo
Arm/Group Description	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later Colchicine: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later	Placebo 1-2 hours prior PCI, followed by placebo 1 hour later Placebo: Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
Measure Participants	120	122
Median (Inter-Quartile Range) [% change]	76	338

3. Secondary Outcome

Title	Percent Change in Post-procedural hsCRP Concentration From Baseline to 22-24 hr After PCI
Time Frame	baseline to 22-24 hr after PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchicine	Placebo
Arm/Group Description	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later Colchicine: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later	Placebo 1-2 hours prior PCI, followed by placebo 1 hour later Placebo: Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
Measure Participants	123	124
Median (Inter-Quartile Range) [% change]	11	66

4. Secondary Outcome

Title	Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI
Time Frame	30 minutes to 1 hour after PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchicine	Placebo
Arm/Group Description	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later Colchicine: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later	Placebo 1-2 hours prior PCI, followed by placebo 1 hour later Placebo: Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
Measure Participants	140	138
Median (Inter-Quartile Range) [% change]	0	0

5. Secondary Outcome

Title	Percent Change in Post-procedural IL-1B Concentration From Baseline to 30 Min -1 hr After PCI
Time Frame	baseline to 22-24 hr after PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchicine	Placebo
Arm/Group Description	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later Colchicine: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later	Placebo 1-2 hours prior PCI, followed by placebo 1 hour later Placebo: Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
Measure Participants	120	122
Median (Inter-Quartile Range) [% change]	0	0

Adverse Events

Time Frame	30 days, 6 months, and yearly for 5 years
Arm/Group Title	Colchicine		Placebo
Arm/Group Description	1.2mg colchicine 1 to 2 hours prior PCI, followed by 0.6mg one hour later Colchicine: Colchicine 1.2mg 1 to 2 hours prior PCI, followed by 0.6mg 1 hour later		Placebo 1-2 hours prior PCI, followed by placebo 1 hour later Placebo: Placebo 1 to 2 hours prior PCI, followed by Placebo 1 hour later
All Cause Mortality
	Colchicine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/141 (0%)		0/139 (0%)
Serious Adverse Events
	Colchicine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/141 (1.4%)		6/139 (4.3%)
Cardiac disorders
Chest pain	1/141 (0.7%)	1	1/139 (0.7%)	1
General disorders
Hemodynamic instabiity	0/141 (0%)	0	2/139 (1.4%)	2
Bleeding	0/141 (0%)	0	1/139 (0.7%)	1
Immune system disorders
Fever	0/141 (0%)	0	1/139 (0.7%)	1
Renal and urinary disorders
Elevated creatinine	0/141 (0%)	0	1/139 (0.7%)	1
Vascular disorders
Ischemic stroke	1/141 (0.7%)	1	0/139 (0%)	0
Other (Not Including Serious) Adverse Events
	Colchicine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/141 (0%)		0/139 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.