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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether colchicine (an anti-inflammatory medication) and thiamine (Vitamin B1) can aid individuals with heart failure due to blocked blood vessels (ischemic heart disease). Researchers aim to determine if colchicine can reduce the risk of heart-related deaths or events and if thiamine can also lower these risks. Participants will first try colchicine to assess tolerance, then may receive either the actual treatments or a placebo (a harmless pill with no active medicine) for comparison. This trial suits those with heart failure from past heart issues, like a heart attack, who experience symptoms that limit daily activities. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Studies have shown that thiamine, or vitamin B1, is generally safe and well tolerated, even at high doses. Research indicates that thiamine does not seem to improve heart function in people with heart failure, but it remains safe with few reported side effects.

Previous patients have tolerated colchicine well at the dose used in this study (0.5 mg daily). The FDA has already approved colchicine for treating conditions like gout and familial Mediterranean fever, which reassures its safety.

Overall, both treatments have demonstrated safety for use in humans, with relatively low reports of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential of colchicine and thiamine for heart failure because they offer novel approaches compared to standard treatments like beta-blockers and ACE inhibitors. Colchicine, traditionally used for gout, may help reduce heart inflammation, which is a different mechanism from typical heart failure meds that mainly focus on blood pressure and fluid balance. Thiamine, a type of vitamin B1, could improve heart function by addressing nutritional deficiencies that sometimes accompany heart failure. These unique approaches could complement existing therapies, potentially leading to better heart failure management.

What evidence suggests that this trial's treatments could be effective for heart failure?

This trial will compare the effects of Colchicine and Thiamine on heart failure. Research suggests that colchicine might help reduce heart problems. One study showed that this drug lowered the risk of heart attacks and other heart issues, which could be promising for people with heart failure. Participants in this trial may receive colchicine or a placebo. Thiamine, a type of vitamin B1, has also been studied for its potential to improve heart function, especially in critically ill heart failure patients. In one study, thiamine was linked to a lower risk of dying in the hospital for these patients. However, results on thiamine's benefits are mixed, as not all studies showed clear improvements. Participants in this trial may receive thiamine or no thiamine. ^{2 6 7 8 9}

Who Is on the Research Team?

Philip G Joseph, M.D.

Principal Investigator

Population Health Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3865826/

Effects of Thiamine on Cardiac Function in Patients With ... In our metaanalysis, thiamine supplementation resulted in a significantly improved net change in LVEF (3.28%, 95% CI: 0.64%, 5.93%) compared with placebo (2 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0965229922000553

The effects of thiamine supplementation on patients with ... Eight studies including 384 patients were included in this review. The results of overall systematic review showed no benefit of thiamine supplementation in HF ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10502219/

Association of vitamin B1 with cardiovascular diseases, all- ... These findings suggested that thiamine had a protective effect against vascular diseases, of which heart failure might be more prominent, and are consistent ...

4. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1162797/full

Association of thiamine administration and prognosis in ... Thiamine supplement is associated with a decreased risk of in-hospital mortality in critically ill patients with heart failure who are admitted to the ICU.

5. pilotfeasibilitystudies.biomedcentral.com pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-018-0342-0

Thiamine versus placebo in older heart failure patients Thiamine deficiency occurs in 33% of patients with HF. However, the effectiveness of thiamine supplementation in HF is not known.

6. ods.od.nih.gov ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/

Thiamin - Health Professional Fact Sheet The authors of one study reported that 33% of 100 patients with chronic heart failure had thiamin deficiency compared to 12% of 50 healthy ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-965/thiamine-vitamin-b1

Thiamine - Uses, Side Effects, And More Heart failure. Giving thiamine by IV or taking thiamine by mouth doesn't seem to reduce the risk of dying or improve heart function in people with heart failure ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2589790X22000324

High-Dose Thiamine Supplementation in Older Patients ... We found high-dose thiamine supplementation to be well tolerated, with potential improvements in biomarker outcomes.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00770107

Thiamine Supplementation to Improve Cardiac Function in ... Thiamine plays a crucial role for normal cardiac function, since severe thiamine deficiency leads to congestive heart failure (wet beriberi).