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

University of Ottawa Heart Institute

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Inflammation; Aortic Stenosis

Treatments: Drug: Colchicine 0.6 mg; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05253794

20210526

Details and patient eligibility

About

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

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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24 participants in 2 patient groups, including a placebo group

Colchicine

Experimental group

Description:

Colchicine 0.6mg PO daily for 6 months

Treatment:

Drug: Colchicine 0.6 mg

Placebo

Placebo Comparator group

Description:

Placebo tablet daily for 6 months

Treatment:

Drug: Placebo