Colchicine for Heart Failure

Overseen By Francesco Moroni, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Virginia

Must not be taking: Immunosuppressives, Anti-inflammatories, Colchicine, others

Disqualifiers: Acute coronary syndromes, Uncontrolled hypertension, Chronic pulmonary disease, 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: 72

Duration: 90±14 days

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a double blind, placebo-controlled pilot trial randomizing patients admitted to the hospital with acutely decompensated heart failure (ADHF) and inflammation to receive either colchicine or matching placebo. Upon enrollment, patients will be randomized 1:1 to receive either the experimental drug (Colchicine) or matching placebo. The regimen in the active arm will consist of 14 days of Colchicine 0.6 mg bid followed by 76±14 days of Colchicine 0.6 mg once per day. Placebo regimen will be analogous, with one pill bid for 14 days followed by one pill once per day for 76 days. Dose reduction for patients with Stage III chronic kidney disease is allowed as detailed in the protocol. At the same time, dose reduction can also be elected in case of GI symptoms. The study team will transiently stop the experimental medication in case of acute kidney injury (AKI), defined per Kidney Disease Improving Global Outcomes (KDIGO) Stage I, as specified in the protocol. These patients will continue with their standard of care for the management of heart failure which consists of a combination of medications that relieve congestion, normalize blood pressure and heart rate, and block the effects of hormones on the heart. The proposed treatment will be in addition to standard of care. No standard of care medications will be withheld. While inflammation is a known risk factor in heart failure, there are no standard anti-inflammatory drugs used in patients with heart failure, as the benefit is not established. The study team will study colchicine, an anti-inflammatory drug, as compares with placebo. Blood will be obtained from the patients in order to measure hsCRP and IL-6. Blood samples will be collected at baseline, 24±6h, 48±6h and 72±6h after treatment initiation, and subsequently at 14±7 days and at study closure. The first four blood samples will be obtained while the subject is still admitted to the hospital. The blood sample at 14±7 days will be obtained during an outpatient encounter. A study closure visit with clinical assessment and experimental drug collection for capsule counting to assess compliance will be conducted at 90±14; the final blood sample will be collected at that time.

Will I have to stop taking my current medications?

The trial does not require you to stop your current heart failure medications, as colchicine will be added to your existing treatment. However, if you are taking certain medications that are contraindicated with colchicine, such as protease inhibitors or specific antibiotics, you may need to stop those.

What data supports the effectiveness of the drug colchicine for heart failure?

A study tested colchicine for 6 months in patients with stable chronic heart failure and found it helped improve their functional status, suggesting it may be beneficial for heart failure. ^{1 2 3 4 5}

Is colchicine generally safe for human use?

Colchicine is generally considered safe for human use, especially in low doses, but it may cause gastrointestinal issues like stomach upset. It has been used safely for conditions like coronary artery disease and pericarditis, although some people may experience side effects such as gastrointestinal discomfort. ^{6 7 8 9 10}

How is the drug colchicine unique for treating heart failure?

Colchicine is unique for heart failure treatment because it is an anti-inflammatory drug that works by affecting white blood cells and reducing inflammation, which is different from most heart failure treatments that focus on improving heart function or fluid balance. It has been used successfully in other cardiovascular conditions, but its role in heart failure is still being explored. ^{8 11 12 13 14}

Research Team

Antonio Abbate, MD

Principal Investigator

UVA Health

Eligibility Criteria

This trial is for hospitalized patients with acutely decompensated heart failure (ADHF) and signs of inflammation. Participants can have a dose reduction if they have Stage III chronic kidney disease or gastrointestinal symptoms, but must stop the medication temporarily if they experience acute kidney injury.

Inclusion Criteria

Expected duration of heart failure at least three months

Willing and able to provide written informed consent

Screening plasma CRP >0.3 mg/dL (3 mg/L) or high-sensitivity CRP >2 mg/L

Exclusion Criteria

Pregnancy

Previous or planned implantation of specific devices or transplantation

Prisoners

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Colchicine or placebo. Colchicine is administered at 0.6 mg twice daily for 14 days, followed by 0.6 mg once daily for 76±14 days.

90±14 days

Inpatient visits for initial 72 hours, outpatient visit at 14±7 days, and study closure visit at 90±14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of hsCRP and IL-6 levels.

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Colchicine

Trial Overview The study tests Colchicine, an anti-inflammatory drug, against a placebo in addition to standard heart failure care. Patients are randomly assigned to either take Colchicine twice daily for two weeks then once daily for about 11 weeks, or a matching placebo schedule.

Participant Groups

Group I: Colchicine 0.6 mg treatment group Experimental Treatment 1 Intervention

Treatment group will be given active drug (0.6mg Colchicine) 2x/day (once if subject has kidney disease) for 14 days. Subsequently treatment group subjects will be given active drug (0.6mg Colchicine) 1x/day for 76 +/- days (or once every other day if subject has kidney disease).

Group II: Control/Placebo group Placebo Group 1 Intervention

Control/Placebo group will be given placebo that looks identical to study drug with no active ingredients and will take 2x/day (once if subject has kidney disease) for 14 days. Subsequently Control/Placebo group will be given placebo 1x/day for 76 +/- days (or once every other day if subject has kidney disease).

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?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Findings from Research

The Impact-Reco programme analyzed prescription rates of heart failure medications in nearly 4,000 stable outpatients, revealing significant increases in the use of angiotensin receptor blockers and beta-blockers, indicating improved treatment practices over time.

Despite these improvements, the study highlighted that certain patient subgroups, particularly the elderly and those with renal failure, still received suboptimal doses of medications, suggesting a need for further enhancements in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in the management of chronic heart failure since the publication of the updated guidelines of the European Society of Cardiology. The Impact-Reco Programme. de Groote, P., Isnard, R., Clerson, P., et al.[2022]

In a study of 25 patients with mild to moderate heart failure, treatment with lacidipine significantly improved key measures of heart function, including peak oxygen consumption and cardiac index, over an 8-week period.

Lacidipine also reduced systemic vascular resistance, suggesting it may help improve blood flow in heart failure patients, making it a potential adjunct therapy alongside standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of lacidipine on peak oxygen consumption, neurohormones and invasive haemodynamics in patients with mild to moderate chronic heart failure. de Vries, RJ., Dunselman, PH., Chin Kon Sung, UG., et al.[2019]

In a study of 12 patients with chronic heart failure, nisoldipine significantly improved cardiac index and reduced mean arterial pressure and systemic vascular resistance after acute administration, indicating its potential to enhance heart function.

The hemodynamic effects of nisoldipine peaked one hour after administration and lasted for up to six hours, suggesting it may provide short-term relief in heart failure symptoms without significantly affecting right atrial and pulmonary pressures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine on the resting and exercise hemodynamics, neurohumoral parameters, and functional capacity of patients with chronic heart failure. Dei Cas, L., Metra, M., Ferrari, R., et al.[2019]

ACE inhibitors are effective in reducing both morbidity and mortality in patients with chronic heart failure (CHF), and they may also help prevent the progression to overt CHF in those with asymptomatic left ventricular dysfunction.

The review provides guidelines for the use of ACE inhibitors in both hospital and general practice settings, while also addressing the role of digoxin and the management of related conditions like angina and arrhythmias in CHF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Problems solved and lives saved? Chronic heart failure. McMurray, J., Francis, M.[2013]

In a study of 267 patients with stable chronic heart failure, colchicine treatment significantly reduced inflammation markers like C-reactive protein and interleukin-6, indicating its anti-inflammatory effects.

However, colchicine did not lead to significant improvements in functional status or exercise tolerance, nor did it reduce the risk of death or hospital stays compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. Deftereos, S., Giannopoulos, G., Panagopoulou, V., et al.[2015]

The LoDoCo2 trial is investigating the efficacy and safety of low-dose colchicine (0.5 mg daily) in 5522 patients with stable coronary artery disease, aiming to confirm its potential for secondary prevention of cardiovascular events.

This study is designed to detect a 30% reduction in major cardiovascular events, such as heart attacks and strokes, while also monitoring for any adverse effects related to colchicine, indicating a thorough approach to evaluating its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. Nidorf, SM., Fiolet, ATL., Eikelboom, JW., et al.[2023]

Low-dose colchicine significantly reduces the rate of major adverse cardiovascular events and acute coronary syndrome in patients with coronary artery disease, based on a review of 11,955 patients across multiple randomized controlled trials.

While colchicine is generally safe, it is associated with an increased risk of gastrointestinal events, highlighting the need for monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Colchicine in Coronary Artery Disease - Systematic Review and Meta-Analysis. Abrantes, AM., Nogueira-Garcia, B., Alves, M., et al.[2021]

Colchicine is considered safe and effective for treating recurrent pericarditis, with specific precautions, although its efficacy for acute pericarditis is less established and requires more research.

The review highlights the importance of understanding potential side effects and drug interactions, suggesting that while colchicine can be beneficial, careful monitoring is necessary during its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine for pericarditis: hype or hope? Imazio, M., Brucato, A., Trinchero, R., et al.[2013]

In a study of 120 patients with their first episode of acute pericarditis, adding colchicine to conventional treatment significantly reduced the recurrence rate from 32.3% to 10.7% over 18 months, indicating its efficacy as an adjunct therapy.

Colchicine was well-tolerated with no serious adverse effects reported, although 8.3% of patients discontinued due to diarrhea, suggesting it is a safe option for managing acute pericarditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Imazio, M., Bobbio, M., Cecchi, E., et al.[2014]

The CORP and CORP-2 trials are set to be the first randomized placebo-controlled studies investigating the efficacy of colchicine in treating recurrent pericarditis, enrolling a total of 360 patients across both trials.

These trials aim to clarify the effectiveness of colchicine in reducing recurrence rates and improving symptoms over 18 months, potentially establishing it as a standard treatment option for patients experiencing recurrent pericarditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CORP (COlchicine for Recurrent Pericarditis) and CORP-2 trials--two randomized placebo-controlled trials evaluating the clinical benefits of colchicine as adjunct to conventional therapy in the treatment and prevention of recurrent pericarditis: study design and rationale. Imazio, M., Cecchi, E., Ierna, S., et al.[2013]

Colchicine has emerged as a promising treatment in cardiovascular disease due to its unique anti-inflammatory mechanism, making it safer than most current anti-inflammatory drugs for patients with heart conditions.

While colchicine is well-established for acute inflammatory conditions like pericarditis, its potential benefits in chronic conditions such as coronary artery disease and heart failure are still being explored, indicating a need for further research in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine in Coronary Artery Disease: An Old Acquaintance in New Attire? Giannopoulos, G., Angelidis, C., Papoutsidakis, N., et al.[2019]

Colchicine, an ancient drug, is gaining attention for its potential benefits in treating cardiovascular diseases, as highlighted by recent studies up to October 2016.

It is crucial for healthcare professionals to understand both the therapeutic advantages and the risks, including side effects and drug interactions, associated with colchicine in cardiac care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teaching an Old Dog New Tricks: Colchicine in Cardiovascular Medicine. Chen, K., Schenone, AL., Borges, N., et al.[2018]

In a multicenter trial involving 240 patients with multiple recurrences of pericarditis, colchicine significantly reduced the rate of recurrent pericarditis compared to placebo, with only 21.6% of patients in the colchicine group experiencing recurrences versus 42.5% in the placebo group (p=0.0009).

Colchicine was found to have a similar safety profile to placebo, with no serious adverse events reported, suggesting it can be safely added to conventional anti-inflammatory treatments for managing recurrent pericarditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Imazio, M., Belli, R., Brucato, A., et al.[2022]

Colchicine has been shown to significantly reduce the risk of recurrence in acute and recurrent pericarditis by half, based on clinical trials involving over 1600 patients.

In larger studies with more than 11,000 patients, colchicine demonstrated a greater than 30% reduction in cardiovascular events, including death and heart attacks, while being generally safe for long-term use at doses of 0.5-1.0 mg daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine and the heart. Imazio, M., Nidorf, M.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Improvement in the management of chronic heart failure since the publication of the updated guidelines of the European Society of Cardiology. The Impact-Reco Programme. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Effects of lacidipine on peak oxygen consumption, neurohormones and invasive haemodynamics in patients with mild to moderate chronic heart failure. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine on the resting and exercise hemodynamics, neurohumoral parameters, and functional capacity of patients with chronic heart failure. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Problems solved and lives saved? Chronic heart failure. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

Low-Dose Colchicine in Coronary Artery Disease - Systematic Review and Meta-Analysis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Colchicine for pericarditis: hype or hope? [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. [2014]

10. United States pubmed.ncbi.nlm.nih.gov

CORP (COlchicine for Recurrent Pericarditis) and CORP-2 trials--two randomized placebo-controlled trials evaluating the clinical benefits of colchicine as adjunct to conventional therapy in the treatment and prevention of recurrent pericarditis: study design and rationale. [2013]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Colchicine in Coronary Artery Disease: An Old Acquaintance in New Attire? [2019]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Teaching an Old Dog New Tricks: Colchicine in Cardiovascular Medicine. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Colchicine and the heart. [2021]