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

Trial Summary

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.

What data supports the effectiveness of the drug Low Dose Colchicine for heart conditions?

Research shows that low-dose colchicine can reduce the risk of heart-related events in people with chronic coronary artery disease, suggesting it might help with heart failure too. It works by reducing inflammation, which is a key factor in heart disease. ^{1 2 3 4 5}

Is colchicine safe for use in humans?

A study tested colchicine for 6 months in patients with stable chronic heart failure, focusing on its anti-inflammatory effects, but it did not specifically address safety outcomes. ^{6 7 8 9 10}

How does the drug Low Dose Colchicine differ from other treatments for heart failure?

Low Dose Colchicine (LoDoCo) is unique for heart failure treatment as it is primarily an anti-inflammatory drug, which may help reduce inflammation in the heart, unlike other treatments that focus on improving heart function or blood flow. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of this research study is to determine the effectiveness of low dose colchicine (LoDoCo) on measures of exercise capacity, physical function, frailty, and quality of life, among patients with heart failure with chronic stable preserved ejection fraction (HFpEF) and systemic inflammation. The use of LoDoCo in this study is considered investigational as it has not been approved by the Food and Drug Administration (FDA) for the treatment of exercise capacity in patients with HFpEF. Participants will undergo a 1-day screening that includes a blood draw and physical examination. If deemed eligible for the study, participants will undergo a baseline visit within 2 weeks of screening visit that includes physical examination, exercise testing, echocardiography and completion of quality-of-life surveys. Participants will also be randomized at this visit (randomly assigned to a group) to receive either LoDoCo or placebo (inactive substance) for 3 months. Participants will be called back at 3 months for repeat physical examination, blood draws, echocardiography, exercise testing and completion of quality-of-life surveys. Each visit will take about 3 hours. Total study duration is about 3 months.

Research Team

Ambarish Pandey, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

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.

Your blood test shows high levels of hs-CRP (a marker of inflammation).

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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 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]

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 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 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]

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]

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]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial. [2023]

3. New Zealand 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. [2022]

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

Colchicine added to standard therapy further reduces fibrosis in pigs with myocardial infarction. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease. [2023]

6. 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]

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

How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure? [2019]

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

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

9. United States 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. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Multi-centre experience on the use of perhexiline in chronic heart failure and refractory angina: old drug, new hope. [2013]

11. 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]

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

A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. [2013]

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

Effect of flecainide on left ventricular ejection fraction. [2019]

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

Echocardiographic and clinical effects of milrinone in dogs with myocardial failure. [2013]

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

Chronic amlodipine treatment during the development of heart failure. [2019]