Colchicine + Thiamine for Heart Failure
(COLT-HF Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Hamilton Health Sciences Corporation
Must not be taking: Cyclosporine, Verapamil, Diltiazem, others
Disqualifiers: Pregnancy, Severe renal dysfunction, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
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
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.
12345Is 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.
678910How 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.
13111213Eligibility 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.
+4 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Thiamine versus no thiamineExperimental Treatment1 Intervention
Randomization to thiamine or to no thiamine in a PROBE design
Group II: Colchicine versus placeboPlacebo Group2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hamilton Health Sciences CorporationHamilton, Canada
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Who Is Running the Clinical Trial?
Hamilton Health Sciences CorporationLead Sponsor
Population Health Research InstituteCollaborator
Canadian Institutes of Health Research (CIHR)Collaborator
References
Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. [2022]We have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months.
Association of thiamine administration and prognosis in critically ill patients with heart failure. [2023]Background: Thiamine deficiency is common in patients with heart failure, and thiamine supplement can benefit these patients. However, the association between thiamine administration and prognosis among critically ill patients with heart failure remains unclear. Thus, this study aims to prove the survival benefit of thiamine use in critically ill patients with heart failure. Methods: A retrospective cohort analysis was performed on the basis of the Medical Information Mart of Intensive Care-Ⅳ database. Critically ill patients with heart failure were divided into the thiamine and non-thiamine groups depending on whether they had received thiamine therapy or not during hospitalization. The association between thiamine supplement and in-hospital mortality was assessed by using the Kaplan-Meier (KM) method and Cox proportional hazard models. A 1:1 nearest propensity-score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPW) were also performed to ensure the robustness of the findings. Results: A total of 7,021 patients were included in this study, with 685 and 6,336 in the thiamine and non-thiamine groups, respectively. The kaplan-meier survival curves indicated that the thiamine group had a lower in-hospital mortality than the none-thiamine group. After adjusting for various confounders, the Cox regression models showed significant beneficial effects of thiamine administration on in-hospital mortality among critically ill patients with heart failure with a hazard ratio of 0.78 (95% confidence interval: 0.67-0.89) in the fully adjusted model. propensity-score matching and probability of treatment weighting analyses also achieved consistent results. Conclusion: 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. Further multicenter and well-designed randomized controlled trials with large sample sizes are necessary to validate this finding.
Thiamine status of elderly patients with cardiac failure including the effects of supplementation. [2013]This study compared the thiamine status of 35 elderly hospital inpatients with cardiac failure (CF) with that of 35 elderly inpatients with other diagnoses (Non-CF). The CF group was then randomly allocated to CF1 group (thiamine treatment, 200 mg per day for 7 days), and CF2 group (non supplemented). The effect of the thiamine treatment on the cardiac failure course was examined. Although there was no significant difference in thiamine status between CF and Non-CF groups, 11.5% of the first group against only 6.0% of the second was deficient with the thiamine pyrophosphate stimulation effect (TPPE) test. The same trend was observed, if NYHA functional assessment was taken into account, thiamine deficiency was more frequent in class 4 than in class 3. No significant difference for thiamin status was observed in patients receiving furosemide treatment and those without furosemide treatment. Although vitamin treatment permitted a significant improvement in thiamine status, the course of the cardiopathy was not significantly different in CF1 (supplemented) and CF2 (non supplemented) groups. Whether systematic thiamine supplementation is indicated in CF patients requires further investigation.
High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF). [2022]Thiamine supplementation may improve cardiac function in older adults with heart failure (HF). Our objectives were to determine the following: (i) the feasibility of conducting a large trial of thiamine supplementation in HF; and (ii) the effects of thiamine on clinical outcomes.
The effects of thiamine supplementation on patients with heart failure: A systematic review and meta-analysis of randomized controlled trials. [2022]Micronutrients can benefit patients with heart failure (HF). Thiamine is a critical vitamin, while the impact of thiamine supplementation on patients with HF remains unclear. Systematic review and meta-analysis were conducted to evaluate the effects of thiamine supplementation on clinical outcomes in patients with HF.
Assessment of the association between colchicine therapy and serious adverse events. [2018]As data that prompted a 2009 labeling change detailing contraindications, precautions, and dosing recommendations for the first branded colchicine product were limited to case reports of myotoxicity and blood dyscrasias ascribed to the drug, we sought to quantify the association of colchicine therapy with serious adverse outcomes in a cohort of insured patients.
Colchicine efficacy and safety for the treatment of cardiovascular diseases. [2022]The emerging role of colchicine in the treatment of cardiovascular diseases is a strong demand for a comprehensive understanding of its efficacy and safety. This meta-analysis and systematic review aimed to study the efficacy in the reduction of adverse cardiovascular outcomes (CO), and the risk of colchicine-related adverse events (CRAEs). Fourteen thousand and nine eighty three patients from 22 randomized controlled trials (RCTs) were included, 9 in patients with coronary artery disease-CAD, 9 in patients with pericarditis, 4 in patients with atrial fibrillation-AF or heart failure. Colchicine was efficacious in the reduction of adverse CO across different settings: pericardial diseases (reduced risk of recurrent pericarditis, 17.6% vs. 35%, RR 0.50, 95% CI 0.41-0.61), CAD (reduced risk of cardiac death, myocardial infarction, stroke,coronary revascularization or hospitalization, 6.1% vs. 8.5%, RR 0.73, 95% CI 0.64-0.83), AF (reduced risk of arrhythmia recurrence, 14.2% vs. 22.7%, RR 0.62, 95% CI 0.44-0.88). Colchicine was associated with increased risk of gastrointestinal CRAEs (11.2% vs. 8.8%, RR 1.87, 95% CI 1.41-2.47) and drug discontinuation (5.4% vs. 3.7%, RR 1.58, 95% CI 1.25-1.99). In both cases, the risk was proportional to the daily dose or duration of treatment, possibly due to early drug discontinuation or tolerance. Other CRAEs (muscle-related, liver,hematologic,cutaneous, infections) were not increased by colchicine, as long as all-cause death (2.2% vs. 1.9%, RR 1.11, 95% CI 0.79-1.54) or non-cardiovascular death (1.5% vs. 1%, RR 1.43, 95% CI 0.93-2.19). Colchicine is efficacious and safe for the treatment of cardiovascular diseases. The risk of gastrointestinal CRAEs and drug discontinuation is not significant if colchicine is used at lower doses (0.5 mg daily) or for longer periods of time (> 6 months).
Colchicine: serious interactions. [2013](1) Renal failure, either pre-existing or induced by a nephrotoxic drug, increases the risk of adverse effects in patients taking colchicine; (2) Combining colchicines with a macrolide (except for spiramycin) carries a risk of life-threatening pancytopenia; (3) Ciclosporin co-administration can aggravate the neuromuscular adverse effects of colchicine; (4) Combining colchicine with lipid-lowering drugs (statins and fibrates) can cause myopathy; (5) Several mechanisms have been implicated: competition for cytochrome P450 or P-glycoprotein, additive adverse effects (especially on muscle), and colchicine accumulation due to a reduction in its renal excretion; (6) Patients with gout should use colchicine only after failure of symptomatic treatment: ice application, paracetamol, and possibly ibuprofen, a nonsteroidal antiinflammatory drug with well-documented adverse effects; (7) If colchicine is nevertheless used, it should be at the minimum effective dose. Close clinical monitoring is required in order to detect early signs of adverse effects, especially diarrhoea, the earliest sign in patients with renal failure and in the elderly.
Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. [2014]Colchicine is effective and safe for the treatment and prevention of recurrent pericarditis and might ultimately serve as the initial mode of treatment, especially in idiopathic cases. The aim of this work was to verify the safety and efficacy of colchicine as an adjunct to conventional therapy for the treatment of the first episode of acute pericarditis.
Colchicine is a safe drug in children with familial Mediterranean fever. [2016]To identify any adverse effects of colchicine in a pediatric patients with familial Mediterranean fever (FMF).
Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure. [2023]We aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF.
Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial. [2023]Thiamin, a water-soluble B-complex vitamin, functions as a coenzyme in macronutrient oxidation and in the production of cellular ATP. Data suggest that thiamin depletion occurs in heart failure (HF). Therefore, thiamin supplementation in HF patients may improve cardiac function.
Infantile Cardiac Beriberi in Rural North East India. [2021]Twenty eight exclusively breastfed infants presented between 1 July, 2017 and 30 June, 2018 with acute heart failure syndrome, with 23 (92%) showing dramatic clinical resolution of shock within 24 hours of receiving intravenous thiamine (100 mg) bolus. Our findings raise awareness for addressing this neglected nutritional disease in North East India.