Colchicine + Thiamine for Heart Failure

(COLT-HF Trial)

Overseen By Philip G Joseph, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Cyclosporine, Verapamil, Diltiazem, others

Disqualifiers: Pregnancy, Severe renal dysfunction, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

2500 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, but you cannot participate if you regularly use colchicine or thiamine for other reasons. Also, you cannot use certain medications like cyclosporine, verapamil, diltiazem, some antifungals, certain antibiotics, or HIV protease inhibitors.

What data supports the effectiveness of the drug Colchicine + Thiamine for heart failure?

Research shows that thiamine (Vitamin B1) supplementation can improve heart function and reduce the risk of death in patients with heart failure, especially those who are critically ill. However, the specific combination of colchicine and thiamine for heart failure has not been directly studied. ^{1 2 3 4 5}

Is colchicine safe for use in humans?

Colchicine is generally safe for treating cardiovascular diseases, but it can cause stomach issues and may lead to stopping the drug if taken in high doses or for short periods. It is important to use it at the lowest effective dose and monitor for side effects, especially in people with kidney problems or those taking certain other medications. ^{6 7 8 9 10}

How does the drug Colchicine + Thiamine for heart failure differ from other treatments?

This treatment is unique because it combines colchicine, which is typically used for gout and inflammation, with thiamine (vitamin B1), which may help improve heart function in patients with heart failure who are deficient due to long-term use of diuretics like furosemide. This combination targets both inflammation and potential vitamin deficiency, which are not commonly addressed together in standard heart failure treatments. ^{1 3 11 12 13}

What is the purpose of this trial?

The goal of this 2x2 factorial clinical trial is to test the efficacy of i) colchicine, and ii) thiamine in heart failure (HF) secondary to ischemic heart disease. The main questions it aims to answer are: * Does colchicine reduce the risk of cardiovascular (CV) death, a HF event, or an ischemic CV event * Does thiamine reduce the risk of cardiovascular (CV) death, or a HF event Participants will undergo the following procedures: * Run-in: All participants will receive colchicine 0.5 mg daily to assess drug tolerance over a 3-4 week period. * Randomization: If colchicine is tolerated during run-in, eligible participants will be randomized in a 2x2 factorial design to receive i) colchicine 0.5mg daily or placebo, and ii) thiamine 300mg daily or no thiamine. * Follow-up: Clinical outcomes, side effects, adverse events, and drug adherence will be captured during follow-up

Research Team

Philip G Joseph, M.D.

Principal Investigator

Population Health Research Institute

Eligibility Criteria

This trial is for adults over 45 with heart failure due to coronary artery disease. They must have a history of heart issues like a past heart attack or surgery, symptoms matching NYHA class II-IV, and reduced heart function (LVEF ≤ 45%) documented in the last year. Both outpatients and stable hospitalized patients can join if they meet certain stability criteria.

Inclusion Criteria

My heart's pumping ability is below 45%.

I am 45 years old or older.

My heart failure treatment has been adjusted according to local medical guidelines.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

All participants receive colchicine 0.5 mg daily to assess drug tolerance

3-4 weeks

Randomization

Eligible participants are randomized to receive colchicine or placebo, and thiamine or no thiamine

Follow-up

Clinical outcomes, side effects, adverse events, and drug adherence are captured

Treatment Details

Interventions

• Colchicine
• Thiamine

Trial Overview The study tests whether colchicine or thiamine reduces cardiovascular death or events in ischemic heart disease-related failure. Participants first try colchicine for tolerance, then are randomly assigned to get either colchicine or placebo, and thiamine or no supplement.

Participant Groups

Group I: Thiamine versus no thiamine Experimental Treatment 1 Intervention

Randomization to thiamine or to no thiamine in a PROBE design

Group II: Colchicine versus placebo Placebo Group 2 Interventions

Randomization to colchicine or placebo

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?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

Population Health Research Institute

Collaborator

Trials

165

Recruited

717,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

In a study of 30 patients with moderate to severe congestive heart failure (CHF) on long-term furosemide therapy, intravenous thiamine (200 mg/d) significantly improved thiamine status and left ventricular ejection fraction (LVEF) after just one week, with LVEF increasing by 22% over the full 7-week intervention.

Thiamine repletion also enhanced diuresis and sodium excretion, indicating that it may help improve heart function and fluid balance in patients suffering from thiamine deficiency due to diuretic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Shimon, I., Almog, S., Vered, Z., et al.[2022]

In a study of 7,021 critically ill patients with heart failure, those who received thiamine supplements had a significantly lower in-hospital mortality rate compared to those who did not, suggesting a survival benefit from thiamine administration.

The analysis showed a hazard ratio of 0.78 for in-hospital mortality in the thiamine group, indicating a 22% reduction in risk, which was consistent across various statistical methods used to ensure the reliability of the results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of thiamine administration and prognosis in critically ill patients with heart failure. Yang, R., Huang, J., Zhao, Y., et al.[2023]

In a study of 70 elderly hospital inpatients, those with cardiac failure showed a higher prevalence of thiamine deficiency compared to those with other diagnoses, particularly in more severe cases of heart failure.

Despite thiamine supplementation improving thiamine status in patients with cardiac failure, it did not lead to significant differences in the progression of their heart condition, suggesting that more research is needed to determine the benefits of routine thiamine supplementation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiamine status of elderly patients with cardiac failure including the effects of supplementation. Pfitzenmeyer, P., Guilland, JC., d'Athis, P., et al.[2013]

A feasibility study involving 24 older adults with heart failure showed that high-dose thiamine supplementation (500 mg) was well tolerated and did not cause any serious adverse events related to the drug.

While the study did not achieve significant improvements in heart function measures like left ventricular ejection fraction, there were nonsignificant positive trends in biomarkers, suggesting that further research on thiamine's effects in heart failure is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF). Wong, EKC., Lee, JY., Chow, J., et al.[2022]

A systematic review of eight studies involving 384 patients found that thiamine supplementation did not significantly improve clinical outcomes in heart failure patients, including measures like left ventricular ejection fraction (LVEF) and quality of life.

Despite the lack of evidence for immediate benefits, the authors suggest that thiamine supplementation may still hold potential for improving cardiac function and symptoms, indicating a need for further research with larger, well-designed trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of thiamine supplementation on patients with heart failure: A systematic review and meta-analysis of randomized controlled trials. Xu, M., Ji, J., Lu, Q., et al.[2022]

In a case-control study of 954 patients with serious adverse outcomes, those with elevated creatine kinase levels or blood dyscrasias had a higher rate of previous colchicine exposure (0.6%) compared to controls (0.2%), suggesting a potential link between colchicine use and these serious conditions.

The study also found that patients experiencing these adverse outcomes had higher hospitalization rates (14.9% vs 5.0%) and were more likely to be taking other medications that could increase the risk of adverse events, supporting the FDA's 2009 warnings about colchicine use in patients with liver or kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the association between colchicine therapy and serious adverse events. Todd, BA., Billups, SJ., Delate, T., et al.[2018]

Colchicine has been shown to effectively reduce adverse cardiovascular outcomes in various conditions, including coronary artery disease and pericarditis, based on a meta-analysis of 14,983 patients from 22 randomized controlled trials.

While colchicine is generally safe, it is associated with an increased risk of gastrointestinal side effects and drug discontinuation, particularly at higher doses; however, these risks can be minimized by using lower doses (0.5 mg daily) or extending treatment duration beyond 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine efficacy and safety for the treatment of cardiovascular diseases. Andreis, A., Imazio, M., Casula, M., et al.[2022]

Patients with renal failure or those taking nephrotoxic drugs are at a higher risk for adverse effects when using colchicine, necessitating careful monitoring and dose adjustments.

Colchicine should only be used in gout patients after other treatments have failed, and if prescribed, it should be at the minimum effective dose to minimize the risk of serious side effects, particularly in vulnerable populations like the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine: serious interactions. [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]

In a study of 153 pediatric patients with familial Mediterranean fever (FMF) over 4 years, colchicine was found to be a safe treatment, with only 14.4% experiencing diarrhea, which could be managed by adjusting the dosage.

A mild and temporary increase in liver enzymes was observed in 11.8% of patients during a 1-year follow-up, but overall, blood counts and kidney function remained normal, indicating that serious adverse effects are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine is a safe drug in children with familial Mediterranean fever. Padeh, S., Gerstein, M., Berkun, Y.[2016]

In a study of 61 hospitalized patients with hypervolemia treated with furosemide, thiamine levels significantly decreased during their hospital stay, particularly in those with heart failure (HF).

The decrease in thiamine levels was not observed at the same rate in patients with renal failure (RF), suggesting that RF may protect against diuretic-induced thiamine loss due to reduced excretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure. Bicer, I., Dizdar, OS., Dondurmacı, E., et al.[2023]

In a study involving 69 patients with heart failure and reduced left ventricular ejection fraction (LVEF), thiamin supplementation did not improve LVEF, quality of life, or exercise capacity after 6 months, despite increased thiamin levels in the supplemented group.

The results suggest that routine thiamin supplementation is not beneficial for patients with heart failure and reduced LVEF, as the placebo group actually showed a slight improvement in LVEF compared to the thiamin group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial. Keith, M., Quach, S., Ahmed, M., et al.[2023]

In a study of 28 exclusively breastfed infants with acute heart failure syndrome, 92% experienced significant improvement in their condition within 24 hours after receiving a 100 mg intravenous thiamine bolus.

This highlights the importance of recognizing and treating thiamine deficiency as a nutritional issue in infants, particularly in regions like North East India where it may be overlooked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infantile Cardiac Beriberi in Rural North East India. Thankaraj, S., Koshy, RM., Ismavel, V.[2021]

References

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

Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Association of thiamine administration and prognosis in critically ill patients with heart failure. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Thiamine status of elderly patients with cardiac failure including the effects of supplementation. [2013]

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

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF). [2022]

5. Scotland pubmed.ncbi.nlm.nih.gov

The effects of thiamine supplementation on patients with heart failure: A systematic review and meta-analysis of randomized controlled trials. [2022]

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

Assessment of the association between colchicine therapy and serious adverse events. [2018]

7. Italy pubmed.ncbi.nlm.nih.gov

Colchicine efficacy and safety for the treatment of cardiovascular diseases. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Colchicine: serious interactions. [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

Colchicine is a safe drug in children with familial Mediterranean fever. [2016]

11. Spain pubmed.ncbi.nlm.nih.gov

Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure. [2023]

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

Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial. [2023]

13. India pubmed.ncbi.nlm.nih.gov

Infantile Cardiac Beriberi in Rural North East India. [2021]