Effect of Colchicine on the Progression of Aortic Valve Stenosis - A Pilot Study (COPAS-Pilot)

COPAS pilot is a pilot single center double blinded randomized study to determine the effect of targeted anti-inflammation therapy using colchicine, on valvular calcification activity using imaging, i.e. aortic valvular NaF uptake. The current proposal uses a randomized design to evaluate the effect of colchicine vs. placebo on valvular calcification activity over 6 months measured using NaF PET

Study Overview

• Status: Completed
• Conditions: Inflammation; Aortic Stenosis
• Intervention / Treatment: Drug: Colchicine 0.6 mg; Drug: Placebo

Detailed Description

COPAS pilot is a pilot single center double blinded randomized study. The investigators will compare the effect of colchicine (0.6 mg daily - intervention arm) vs. placebo (control group) on the 18F NaF aortic valve uptake in patients with mild to moderate AS defined by a mean pressure gradient measured using transthoracic echocardiography (TTE) between 15-25 mm Hg after a 6-month period of treatment. The investigators plan to enroll 12 patients (6 males/6 females) in each arm (total sample size: 24 patients). Primary endpoint is the change in 18FNaF aortic valve uptake between baseline and 6 months in each arm. Parameters of interest are the maximal and total standard uptake values (SUVs) and tissue-to background ratios (TBRs) at the level of the aortic valve.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. mild to moderate aortic stenosis defined by a mean pressure gradient using transthoracic echocardiography (TTE) between 15-25mmHg.
2. age greater than18 years;
3. given informed consent.

Exclusion Criteria:

1. bicuspid aortic valve
2. associated moderate to severe aortic regurgitation
3. associated other valvular pathology of moderate or greater severity
4. LV dysfunction (EF<50%);
5. decompensated heart failure;
6. active infection (e.g. pneumonia, active skin infections, and on antibiotics);
7. chronic diarrhea;
8. immune compromise (e.g. recurrent infection);
9. history of cancer within the last 3 years (other than a successfully treated cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix).
10. active inflammatory conditions (e.g. rheumatoid arthritis, chronic inflammatory bowel disease, SLE, systemic anti-inflammatory therapy (e.g. prednisone, methotrexate));
11. pregnancy (all women of child bearing potential will have a negative BHCG test;
12. breastfeeding;
13. Women of childbearing potential who refuse to use two forms of contraception (this includes at least one form of highly effective and one effective method of contraception) throughout the study OR men capable of fathering a child who refuse to use contraception.
14. glomerular filtration rate (GFR) <50 ml/min/1.72m2;
15. Use of p-glycoprotein inhibitor (e.g. cyclosporine, verapamil, or quinidine) or a strong CYP3A4 inhibitor (e.g. ritonavir, clarithromycin, or ketoconazole);
16. Hemoglobin < 105(women) <110 (men) g/L; WBC < 3.0x 10(9)/L, platelet count< 110x 10(9)/L;
17. Patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease or with alanine aminotransferase (ALT) levels greater than 3 times the upper limit of normal.
18. unable to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; Colchicine 0.6mg PO daily for 6 months	Drug: Colchicine 0.6 mg; oral tablet daily for 6 months
Placebo Comparator: Placebo; Placebo tablet daily for 6 months	Drug: Placebo; oral tablet daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in aortic valve calcification activity	Change in valvular calcification activity as measured by NaF uptake by Target to Background Ratio (TBR) on PET/CT imaging	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in aortic valve calcification	Change is the degree of aortic valve calcification measured using CT scan (calcium score) and expressed in arbitrary units	One year

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Investigators: Principal Investigator: David Messika-Zetioun@ottawaheart.ca, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): January 20, 2025

Study Registration Dates

• First Submitted: February 1, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): February 24, 2022

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: colchicine
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Pathological Conditions, Signs and Symptoms; Aortic Valve Stenosis; Inflammation; Heterocyclic Compounds; Alkaloids; Colchicine
• Other Study ID Numbers: 20210526

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No