Colchicine for Aortic Stenosis

(COPAS-Pilot Trial)

Overseen By David Messika-Zeitoun

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Antibiotics, Prednisone, Methotrexate, others

Disqualifiers: Cancer, Heart failure, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how colchicine, an anti-inflammatory medicine, affects calcium buildup in heart valves for people with aortic stenosis. Aortic stenosis occurs when heart valves narrow, hindering blood flow. The trial will compare colchicine to a placebo over six months to determine if it reduces calcium buildup. People with mild to moderate aortic stenosis, identified by specific heart tests, might be suitable for this study. As a Phase 2, Phase 3 trial, the research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to significant advancements in heart health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain medications like p-glycoprotein inhibitors or strong CYP3A4 inhibitors.

Is there any evidence suggesting that colchicine is likely to be safe for humans?

Research has shown that colchicine is generally safe for people. Studies have found that patients tolerate it well after heart surgery, and it helps prevent irregular heartbeats, known as atrial fibrillation. In these studies, colchicine did not cause major side effects. It has also been used in patients with heart conditions to lower the risk of further heart problems.

While colchicine is also used for other conditions like gout, no treatment is completely without risk. Some studies suggest a small chance of side effects, but these are rare. Overall, colchicine has a good safety record in these situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aortic stenosis?

Colchicine is unique because it offers a new approach to treating aortic stenosis, a condition traditionally managed with surgical procedures like valve replacement or repair. Unlike these standard interventions, colchicine is an anti-inflammatory drug that works by reducing inflammation in the heart, which could potentially slow the progression of aortic stenosis. Researchers are excited about colchicine because it provides a non-surgical option that might improve heart function and quality of life for patients. Additionally, colchicine is taken orally, making it a convenient alternative to invasive treatments.

What evidence suggests that colchicine might be an effective treatment for aortic stenosis?

Research has shown that colchicine might help reduce inflammation linked to heart issues. In people with stable atherosclerosis, where arteries harden, taking a low dose of colchicine lowered major heart-related problems by 31%. This trial will test colchicine for potential benefits in heart valve issues, such as aortic stenosis. Colchicine has prevented irregular heartbeats after heart surgery, suggesting its usefulness in heart treatments. Although one heart attack study did not show improved results with colchicine, its ability to reduce inflammation remains promising for aortic stenosis. Participants in this trial will receive either colchicine or a placebo to evaluate its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

David [e-mail]

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

Adults over 18 with mild to moderate aortic stenosis (15-25mmHg pressure gradient) can join this study. They must be able to consent and agree to use two forms of contraception if capable of childbearing. Excluded are those with severe heart issues, liver disease, immune compromise, certain medication use, recent cancer (except some skin cancers), pregnancy, breastfeeding or poor kidney function.

Inclusion Criteria

My heart valve narrowing is mild to moderate.

I am older than 18 years.

Given informed consent

Exclusion Criteria

Breastfeeding

I am not taking medications like cyclosporine, verapamil, or ketoconazole.

I have moderate or severe heart valve problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive colchicine or placebo daily for 6 months to assess the effect on aortic valve calcification

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine

Trial Overview The COPAS pilot is testing whether Colchicine can slow down the hardening of the aortic valve by comparing it against a placebo. Participants will be randomly assigned to one of these two groups in a double-blind manner and monitored for 6 months using NaF PET imaging.

How Is the Trial Designed?

Group I: Colchicine Experimental Treatment 1 Intervention

Colchicine 0.6mg PO daily for 6 months

Group II: Placebo Placebo Group 1 Intervention

Placebo tablet daily for 6 months

Colchicine is already approved in United States for the following indications:

Approved in United States as Colcrys for:

• Gout
• Familial Mediterranean Fever

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Published Research Related to This Trial

A new compound, 1,7-bis(4-hydroxyphenyl)-3-hydroxy-1,3-heptadien-5-one, isolated from Alpinia blepharocalyx seeds, demonstrated strong inhibition of platelet aggregation in human blood, suggesting potential as an antiplatelet agent.

Another compound, identified as compound 3, also effectively inhibited various forms of platelet aggregation, indicating that these compounds could be valuable in developing treatments for conditions related to excessive blood clotting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new antiplatelet diarylheptanoid from Alpinia blepharocalyx. Doug, H., Chen, SX., Xu, HX., et al.[2014]

The crude aqueous extract of parsley significantly inhibits platelet aggregation in vitro and ex vivo, suggesting its potential as a natural anti-platelet agent, which could help in managing cardiovascular diseases.

Oral administration of parsley extract not only reduced platelet aggregation but also prolonged bleeding time in experimental animals, indicating its efficacy without affecting platelet count, likely due to its polyphenolic compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats. Gadi, D., Bnouham, M., Aziz, M., et al.[2022]

Garlic powder, tomato extract, and their mixture were found to have anti-thrombotic effects in a rat model, as they delayed blood clotting times and reduced certain inflammatory markers after 7 days of treatment.

Histological analysis indicated that these treatments improved thrombosis conditions in the aorta and lungs, although combining garlic and tomato extract did not enhance the effects compared to using them individually.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of the antithrombotic effect through activated endothelium of garlic powder and tomato extracts using a rodent model of collagen and epinephrine induced thrombosis. Kim, L., Lim, Y., Park, SY., et al.[2020]

The aqueous extract of onion demonstrated significant antiplatelet effects in both rat and human platelets, with IC(50) values indicating effective inhibition of platelet aggregation induced by various agents, such as collagen and thrombin.

The mechanism of action includes reducing arachidonic acid release, inhibiting thromboxane A2 (TXA2) synthase activity, and blocking TXA2/PGH2 receptors, all without causing cytotoxic effects on platelets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism for antiplatelet effect of onion: AA release inhibition, thromboxane A(2)synthase inhibition and TXA(2)/PGH(2)receptor blockade. Moon, CH., Jung, YS., Kim, MH., et al.[2006]

A meta-analysis of 11 trials with 477 participants found that Ginkgo biloba extract did not provide a clinically significant improvement in walking distance for patients with intermittent claudication, showing only a marginal increase of 64.5 meters compared to placebo.

Despite being a vasoactive agent used for symptom relief, the results suggest that Ginkgo biloba may not be an effective treatment option for enhancing walking capacity in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the Cochrane library: Ginkgo biloba for intermittent claudication. Nicolaï, SP., Gerardu, VC., Kruidenier, LM., et al.[2012]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40659682/

Colchicine in patients with aortic stenosis undergoing ... The prespecified imaging endpoint, subclinical leaflet thrombosis, was detected in 13 of 48 patients (27%) in the colchicine group versus 26 of ...

2. nature.com nature.com/articles/s41467-025-61916-6

Colchicine in patients with aortic stenosis undergoing ... Randomized trials in patients after cardiac surgery indicated that colchicine is safe and effective in the prevention of atrial fibrillation ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11229522/

Studying the efficacy of low-dose colchicine on clinical ... This study revealed that the addition of colchicine did not yield a significant benefit in enhancing the outcomes of patients with STEMI.

4. jacc.org jacc.org/doi/10.1016/j.jacc.2023.05.055

Low-Dose Colchicine for Secondary Prevention of ... Low-dose colchicine (0.5 mg/d orally) has been shown to safely lower major adverse cardiovascular events by 31% among those with stable atherosclerosis and by ...

5. ahajournals.org ahajournals.org/doi/10.1161/JAHA.125.043791

Preoperative Colchicine and Conduction Disturbances ... This study found that preoperative colchicine was associated with a reduced onset of new and worsening atrioventricular block/left bundle‐branch ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12259991/

Colchicine in patients with aortic stenosis undergoing ... Randomized trials in patients after cardiac surgery indicated that colchicine is safe and effective in the prevention of atrial fibrillation ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12554186/

Colchicine and cardiovascular outcomes in MINOCA Among secondary outcomes, colchicine users had significantly lower rates of AMI recurrence and all-cause mortality. Heart failure events and all ...

8. jacc.org jacc.org/doi/10.1016/j.jacc.2025.08.025

An Exploratory Substudy of the LoDoCo2 Trial | JACC In addition to increasing the risk for hematologic malignancies, CH is associated with up to a twofold increased risk of cardiovascular events ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2021372

Colchicine in Patients with Chronic Coronary Disease Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT04870424

Study Details | NCT04870424 | Colchicine for Patients With ... Colchicine has proven safe and effective in the prevention of atrial fibrillation after cardiac surgery. The anti-inflammatory effects of colchicine may ...