LoDoCo for Heart Failure

Overseen By Ambarish Pandey, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Pregnancy, Renal impairment, Severe valvular 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: 4

Duration: 3 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a low dose of colchicine can improve exercise capacity, physical function, frailty, and quality of life in people with heart failure and stable heart function. Participants will randomly receive either colchicine or a placebo daily for three months. This study suits those diagnosed with heart failure with preserved ejection fraction and ongoing systemic inflammation. Participants must be able to walk and perform exercise tests. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should be on stable doses of heart failure-specific medications and weight loss medications for at least one month before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking a low dose of colchicine, specifically 0.5 mg daily, is generally safe. Studies have safely used this dose in individuals with heart conditions. For example, research involving patients with ongoing heart disease found that colchicine reduced heart-related issues without causing major problems. Additionally, long-term studies on heart disease prevention demonstrated that colchicine effectively lowered the risk of serious heart events, again with good safety results. While no treatment is completely without risk, current evidence suggests that colchicine is safe at this low dose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Low dose colchicine is unique because it offers a fresh approach to treating heart failure by targeting inflammation, which is a growing area of interest in heart disease management. Unlike typical heart failure treatments such as beta-blockers and ACE inhibitors that focus on managing symptoms and improving heart function directly, colchicine is an anti-inflammatory medication traditionally used for gout. Researchers are excited about colchicine because it's leveraging its anti-inflammatory properties to potentially reduce heart inflammation, offering a new mechanism of action that could complement existing heart failure therapies. This could lead to improved outcomes for patients with heart failure by addressing an underlying cause of heart damage.

What evidence suggests that low dose colchicine might be an effective treatment for heart failure?

This trial will compare low-dose colchicine with a placebo to evaluate its effects on heart failure. Research has shown that low-dose colchicine can reduce inflammation in people with coronary artery disease by lowering levels of CRP, a protein that indicates inflammation, which is promising for heart health. In those with stable coronary artery disease, colchicine lowered the risk of major heart problems by 23% to 31%. Although colchicine is not yet approved specifically for heart failure with preserved ejection fraction (HFpEF), its ability to reduce inflammation might improve heart function and quality of life for these patients. These findings suggest that colchicine could be useful in managing conditions where inflammation is a factor. ^{2 4 5 6 7}

Who Is on the Research Team?

Ambarish Pandey, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for people over 50 with heart failure (HFpEF) and inflammation, who've been diagnosed within the last 6 months. They must have had a recent heart failure episode and be able to do exercise tests. Participants should not be pregnant, planning pregnancy, or have severe kidney issues or liver enzymes more than 2.5 times the normal limit.

Inclusion Criteria

You agreed to take part in the study before it started.

You have a consistent level of physical activity.

My heart failure medications have not changed in the last month.

Exclusion Criteria

Do not otherwise meet the inclusion criteria

Women who are pregnant, breastfeeding, or may be considering pregnancy during the study period

Unable to perform cardiopulmonary exercise testing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Baseline and Randomization

Baseline assessments including physical examination, exercise testing, echocardiography, and quality-of-life surveys. Participants are randomized to receive either LoDoCo or placebo.

Within 2 weeks of screening

1 visit (in-person)

Treatment

Participants receive either LoDoCo or placebo for 3 months. Assessments include physical exams, blood tests, echocardiography, exercise testing, and quality-of-life surveys.

3 months

1 visit (in-person) at 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including repeat assessments of physical exams, blood tests, echocardiography, exercise testing, and quality-of-life surveys.

3 months

1 visit (in-person) at 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Low Dose Colchicine
• Placebo

Trial Overview The study is testing if Low Dose Colchicine (LoDoCo) can improve exercise ability and quality of life in patients with HFpEF and inflammation compared to a placebo. It's randomized, meaning participants are put into either the LoDoCo group or placebo group by chance.

How Is the Trial Designed?

Group I: Low dose colchicine Experimental Treatment 1 Intervention

Low dose colchicine 0.5 mg once a day orally for 3 months

Group II: Placebo Placebo Group 1 Intervention

Placebo once a day orally for 3 months

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

Approved in United States as Lodoco for:

• Reducing the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic cardiovascular disease (ASCVD) or with multiple risk factors for cardiovascular disease

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Milrinone, administered at effective dosages of 0.5 to 1.0 mg/kg over 14 days, significantly improved left ventricular function in dogs with myocardial failure, demonstrating its efficacy as a treatment.

The study found that tolerance to milrinone did not develop over the 4-week period, and while some dogs experienced clinical improvement, there were also instances of exacerbated ventricular dysrhythmias, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Echocardiographic and clinical effects of milrinone in dogs with myocardial failure. Kittleson, MD., Pipers, FS., Knauer, KW., et al.[2013]

In a study of 125 elderly patients with severe congestive heart failure (CHF) treated with spironolactone (SPL), adverse effects such as hyperkalemia and impaired renal function were found to be more common than previously reported, with 36% experiencing elevated potassium levels and 55% showing significant increases in serum creatinine.

The study highlights the need for careful monitoring and management of SPL treatment, especially in patients with an LVEF <20%, and suggests discontinuing potassium supplements and adjusting diuretic doses to mitigate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure? Svensson, M., Gustafsson, F., Galatius, S., et al.[2019]

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]

In a study of 102 patients with idiopathic dilated cardiomyopathy, those treated with prednisone showed a significant improvement in heart function, with 53% experiencing an increase in ejection fraction compared to 27% in the control group after three months.

However, the overall clinical benefit of prednisone was marginal, as improvements were small, temporary, and accompanied by important side effects, leading to the conclusion that it should not be used as standard therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. Parrillo, JE., Cunnion, RE., Epstein, SE., et al.[2013]

In a study of 36 patients with left ventricular dysfunction, oral flecainide did not significantly change left ventricular ejection fraction (LVEF) after 7 days of treatment, regardless of whether the dosage was 200 mg or 300 mg per day.

However, the study highlighted that patients with severe LV dysfunction (LVEF less than 30%) experienced more severe cardiac adverse effects, indicating that caution is needed when prescribing flecainide in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of flecainide on left ventricular ejection fraction. Brembilla-Perrot, B., Amor, M., Auque, F., et al.[2019]

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]

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 151 patients with chronic heart failure and/or refractory angina, 58.9% reported feeling better on perhexiline therapy, indicating its efficacy in providing symptomatic relief.

Monitoring drug levels is crucial, as 68.8% of patients had levels within the therapeutic range, and those with refractory angina were more likely to respond positively to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-centre experience on the use of perhexiline in chronic heart failure and refractory angina: old drug, new hope. Phan, TT., Shivu, GN., Choudhury, A., et al.[2013]

In the LoDoCo2 trial involving 5522 patients with chronic coronary disease, low-dose colchicine (0.5 mg daily) significantly reduced cardiovascular deaths without adversely affecting specific causes of death, indicating its safety in this context.

Most deaths during the study were due to non-cardiovascular causes, with age over 65 being a strong predictor of non-cardiovascular mortality, highlighting the role of comorbidities in overall mortality for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial. Opstal, TSJ., Nidorf, SM., Fiolet, ATL., et al.[2023]

In a study of 3164 patients with chronic heart failure, most were able to tolerate high doses of lisinopril, with only 4.2% unable to reach the required medium doses due to hypotension or renal issues.

The results suggest that ACE inhibitors like lisinopril can be safely and effectively used at higher doses in patients with chronic heart failure, including those at higher risk for intolerance, indicating that more aggressive treatment strategies should be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival. Massie, BM., Armstrong, PW., Cleland, JG., et al.[2019]

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]

In the LoDoCo2 trial involving 1776 participants over a median of 32.7 months, colchicine 0.5 mg daily significantly reduced the risk of cardiovascular events without adversely affecting renal function, as there were no changes in creatinine or blood urea nitrogen levels.

Colchicine was associated with mild elevations in liver enzymes (ALT) and creatine kinase (CK), but no severe elevations were observed, indicating that while there are some changes in liver and muscle markers, they are not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Years-Long Exposure to Low-Dose Colchicine on Renal and Liver Function and Blood Creatine Kinase Levels: Safety Insights from the Low-Dose Colchicine 2 (LoDoCo2) Trial. van Broekhoven, A., Mohammadnia, N., Silvis, MJM., et al.[2022]

In a study involving pigs with induced myocardial infarction, colchicine treatment for 30 days significantly reduced fibrosis in the infarct zone compared to standard therapy alone, indicating its potential to improve heart tissue healing after a heart attack.

While colchicine showed a trend towards better myocardial salvage, it did not lead to significant changes in left ventricular remodeling, such as volume or ejection fraction, suggesting its primary benefit lies in reducing scar tissue rather than altering heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine added to standard therapy further reduces fibrosis in pigs with myocardial infarction. Aimo, A., Martinez-Falguera, D., Barison, A., et al.[2023]

In a study involving 10,830 patients with coronary artery disease, low-dose colchicine was found to provide a median 10-year absolute risk reduction of 4.6% for major adverse cardiovascular events (MACE) and 8.6% for MACE+, indicating significant individual benefits based on patient risk profiles.

The benefits of low-dose colchicine were comparable to intensified strategies for lowering LDL cholesterol and blood pressure, suggesting it can be an effective option for patients already receiving standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease. Burger, PM., Dorresteijn, JAN., Fiolet, ATL., et al.[2023]

Chronic treatment with amlodipine significantly improved left ventricular stroke volume and reduced vascular resistance in an animal model of congestive heart failure (CHF), indicating enhanced heart function and blood flow.

Amlodipine treatment also lowered elevated levels of norepinephrine and endothelin, which are associated with heart stress, and improved the contractile function of heart cells, suggesting a beneficial neurohormonal effect in CHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic amlodipine treatment during the development of heart failure. Spinale, FG., Mukherjee, R., Krombach, RS., et al.[2019]

Citations

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

Low-Dose Colchicine for Secondary Prevention of ... In patients with coronary artery disease taking aspirin and statins, colchicine incrementally reduces CRP levels as well as low-attenuation ...

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

Colchicine in Patients with Chronic Coronary Disease Patients were not eligible if they had moderate-to-severe renal impairment, severe heart failure, severe valvular heart disease, or known side effects from ...

3. ccjm.org ccjm.org/content/92/10/609

Low-dose colchicine for management of coronary artery ... Although canakinumab failed to gain FDA approval as a cardiovascular therapy, CANTOS provided an important proof of concept that it was possible ...

4. academic.oup.com academic.oup.com/eurheartj/article/46/26/2552/8123897

Long-term trials of colchicine for secondary prevention of ... Colchicine in patients with coronary artery disease. This updated meta-analysis (including CLEAR-SYNERGY) shows the large benefits of low-dose ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11872516/

Potential Impact of Colchicine on Atherosclerotic ... Central Illustration. ... Colchicine lowers the risk of major adverse cardiovascular events in stable coronary artery disease by 23% to 31% beyond ...

6. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.124.319851

Colchicine's Role in Cardiovascular Disease Management Low-dose colchicine 0.5 mg daily had no effect on severely elevated albuminuria or major adverse kidney events in 160 people with type 2 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12184580/

A Secondary Analysis of the LoDoCo2 Trial - PMC The LoDoCo2 (Low‐Dose Colchicine 2) trial showed that colchicine reduced the risk for cardiovascular events in patients with chronic coronary syndrome.