Colchicine for Heart Failure
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of Virginia
Must not be taking: Immunosuppressives, Anti-inflammatories, Colchicine, others
Disqualifiers: Acute coronary syndromes, Uncontrolled hypertension, Chronic pulmonary disease, others
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This is a double blind, placebo-controlled pilot trial randomizing patients admitted to the hospital with acutely decompensated heart failure (ADHF) and inflammation to receive either colchicine or matching placebo.
Upon enrollment, patients will be randomized 1:1 to receive either the experimental drug (Colchicine) or matching placebo. The regimen in the active arm will consist of 14 days of Colchicine 0.6 mg bid followed by 76±14 days of Colchicine 0.6 mg once per day. Placebo regimen will be analogous, with one pill bid for 14 days followed by one pill once per day for 76 days. Dose reduction for patients with Stage III chronic kidney disease is allowed as detailed in the protocol. At the same time, dose reduction can also be elected in case of GI symptoms. The study team will transiently stop the experimental medication in case of acute kidney injury (AKI), defined per Kidney Disease Improving Global Outcomes (KDIGO) Stage I, as specified in the protocol.
These patients will continue with their standard of care for the management of heart failure which consists of a combination of medications that relieve congestion, normalize blood pressure and heart rate, and block the effects of hormones on the heart. The proposed treatment will be in addition to standard of care. No standard of care medications will be withheld. While inflammation is a known risk factor in heart failure, there are no standard anti-inflammatory drugs used in patients with heart failure, as the benefit is not established. The study team will study colchicine, an anti-inflammatory drug, as compares with placebo.
Blood will be obtained from the patients in order to measure hsCRP and IL-6. Blood samples will be collected at baseline, 24±6h, 48±6h and 72±6h after treatment initiation, and subsequently at 14±7 days and at study closure. The first four blood samples will be obtained while the subject is still admitted to the hospital. The blood sample at 14±7 days will be obtained during an outpatient encounter. A study closure visit with clinical assessment and experimental drug collection for capsule counting to assess compliance will be conducted at 90±14; the final blood sample will be collected at that time.
Will I have to stop taking my current medications?
The trial does not require you to stop your current heart failure medications, as colchicine will be added to your existing treatment. However, if you are taking certain medications that are contraindicated with colchicine, such as protease inhibitors or specific antibiotics, you may need to stop those.
What data supports the effectiveness of the drug colchicine for heart failure?
A study tested colchicine for 6 months in patients with stable chronic heart failure and found it helped improve their functional status, suggesting it may be beneficial for heart failure.
12345Is colchicine generally safe for human use?
Colchicine is generally considered safe for human use, especially in low doses, but it may cause gastrointestinal issues like stomach upset. It has been used safely for conditions like coronary artery disease and pericarditis, although some people may experience side effects such as gastrointestinal discomfort.
678910How is the drug colchicine unique for treating heart failure?
Colchicine is unique for heart failure treatment because it is an anti-inflammatory drug that works by affecting white blood cells and reducing inflammation, which is different from most heart failure treatments that focus on improving heart function or fluid balance. It has been used successfully in other cardiovascular conditions, but its role in heart failure is still being explored.
811121314Eligibility Criteria
This trial is for hospitalized patients with acutely decompensated heart failure (ADHF) and signs of inflammation. Participants can have a dose reduction if they have Stage III chronic kidney disease or gastrointestinal symptoms, but must stop the medication temporarily if they experience acute kidney injury.Inclusion Criteria
Expected duration of heart failure at least three months
Willing and able to provide written informed consent
Screening plasma CRP >0.3 mg/dL (3 mg/L) or high-sensitivity CRP >2 mg/L
+2 more
Exclusion Criteria
Pregnancy
Previous or planned implantation of specific devices or transplantation
Prisoners
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either Colchicine or placebo. Colchicine is administered at 0.6 mg twice daily for 14 days, followed by 0.6 mg once daily for 76±14 days.
90±14 days
Inpatient visits for initial 72 hours, outpatient visit at 14±7 days, and study closure visit at 90±14 days
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of hsCRP and IL-6 levels.
4 weeks
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The study tests Colchicine, an anti-inflammatory drug, against a placebo in addition to standard heart failure care. Patients are randomly assigned to either take Colchicine twice daily for two weeks then once daily for about 11 weeks, or a matching placebo schedule.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Colchicine 0.6 mg treatment groupExperimental Treatment1 Intervention
Treatment group will be given active drug (0.6mg Colchicine) 2x/day (once if subject has kidney disease) for 14 days. Subsequently treatment group subjects will be given active drug (0.6mg Colchicine) 1x/day for 76 +/- days (or once every other day if subject has kidney disease).
Group II: Control/Placebo groupPlacebo Group1 Intervention
Control/Placebo group will be given placebo that looks identical to study drug with no active ingredients and will take 2x/day (once if subject has kidney disease) for 14 days. Subsequently Control/Placebo group will be given placebo 1x/day for 76 +/- days (or once every other day if subject has kidney disease).
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:
UVA HealthCharlottesville, VA
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Who Is Running the Clinical Trial?
University of VirginiaLead Sponsor
References
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]Recent studies have shown that prescription rates and doses of recommended drugs for chronic heart failure (CHF) are not optimal in daily practice. The aim of the Impact-Reco programme was to analyse prescription rates of CHF drugs in stable outpatients with CHF related to left ventricular (LV) systolic dysfunction in two similar surveys in France.
Effects of lacidipine on peak oxygen consumption, neurohormones and invasive haemodynamics in patients with mild to moderate chronic heart failure. [2019]To evaluate the efficacy and safety of the second generation dihydropyridine calcium channel blocker lacidipine in patients with heart failure.
Acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine on the resting and exercise hemodynamics, neurohumoral parameters, and functional capacity of patients with chronic heart failure. [2019]The acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine were studied in patients with chronic heart failure (LV EF
Problems solved and lives saved? Chronic heart failure. [2013]Chronic heart failure (CHF) is common, disabling and deadly. Recent studies show that ACE inhibitors reduce morbidity and mortality in all grades of CHF and may even delay or prevent the onset of overt CHF in patients with asymptomatic left ventricular dysfunction. In this review, guidelines are given for how to use these drugs both in hospital and in general practice. New evidence on the benefits of digoxin is also considered, and the management of concomitant problems such as angina and arrhythmias in patients with CHF is discussed.
Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. [2015]The purpose of this study was to test the efficacy of a 6-month course of anti-inflammatory treatment with colchicine in improving functional status of patients with stable chronic heart failure (CHF).
The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. [2023]Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease. RATIONALE AND DESIGN: The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease. LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. CONCLUSION: The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.
Low-Dose Colchicine in Coronary Artery Disease - Systematic Review and Meta-Analysis. [2021]Background: Recent studies have revealed the benefits of using colchicine, a drug with anti-inflammatory properties, in coronary artery disease (CAD). This study systematically reviewed the benefits and risks of low-dose colchicine in patients with CAD. Methods and Results: We searched for randomized controlled trials (RCTs) in MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases (March 2020). Efficacy and safety outcomes were evaluated. Estimates are expressed as risk ratios (RRs) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with I2 test. Confidence in the pooled evidence was appraised using the GRADE framework. Colchicine reduced the rate of major adverse cardiovascular events (RR 0.65; 95% CI 0.49-0.86; 6 RCTs; I2=50%; 11,718 patients; GRADE, moderate confidence), acute coronary syndrome (RR 0.64; 95% CI 0.46-0.90; I2=47%; 7 RCTs; 11,955 patients; GRADE, very low confidence), stroke (RR 0.49; 95% CI 0.30-0.78; I2=0%; 6 RCTs; 11,896 patients; GRADE, moderate confidence), and cardiovascular interventions (RR 0.61; 95% CI 0.42-0.89; I2=40%; 4 RCTs; 11,284 patients; GRADE, high confidence). Colchicine did not increase the risk of adverse events, except for gastrointestinal events (RR 1.54; 95% CI 1.11-2.13; I2=72%; 9 RCTs; 12,374 patients; GRADE, very low confidence). Conclusions: Low-dose colchicine in patients with CAD is associated with beneficial effects on prognosis, although an increased risk of gastrointestinal events was confirmed.
Colchicine for pericarditis: hype or hope? [2013]Colchicine has been effectively used in the treatment of several inflammatory conditions, such as gouty attacks, serositis related to familial Mediterranean fever, Behçet syndrome, and more recently also in acute and recurrent pericarditis. Growing evidence has shown that the drug may be useful to treat an acute attack and may be a way to cope with the prevention of pericarditis in acute and recurrent cases and after cardiac surgery. Nevertheless, clinicians are often sceptical about the efficacy of the drug, and concerns have risen on possible side effects and tolerability. In this review, we analyse current evidence to support the use of the drug, as well as possible harms and risks related to drug interactions, reaching the conclusion that colchicine is safe and useful in recurrent pericarditis, if specific precautions are followed, although less evidence supports its use for the treatment of acute pericarditis, where colchicine remains optional and there is a need for further multicentre confirmatory studies. This paper also reviews specific dosing and precautions for the clinical use.
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.
CORP (COlchicine for Recurrent Pericarditis) and CORP-2 trials--two randomized placebo-controlled trials evaluating the clinical benefits of colchicine as adjunct to conventional therapy in the treatment and prevention of recurrent pericarditis: study design and rationale. [2013]Colchicine appears to be safe and effective in the treatment and prevention of recurrent pericarditis after failure of conventional therapies in case reports and non-randomized observational studies without control groups. On this basis, colchicine has been proposed as a therapeutic choice in the 2004 guidelines of the European Society of Cardiology. However, the exact number of responders is unknown, and no randomized placebo-controlled trial is available to guide the management of recurrent pericarditis. Moreover, some authors recommend the use of the drug at the first recurrence, whereas others propose to consider the drug only after failure of conventional therapies for the second or subsequent recurrence.
Colchicine in Coronary Artery Disease: An Old Acquaintance in New Attire? [2019]Colchicine has recently gained considerable attention in the field of cardiovascular research, after a number of studies showed that it may be of use in several settings of cardiovascular disease, including chronic coronary artery disease and following stent implantation. Its unique anti-inflammatory mechanism of action makes it safe to use in patients with cardiovascular disease, unlike most--if not all--currently available antiinflammatory agents. While its prophylactic and therapeutic value is well-established in certain conditions involving an acute inflammatory response, e.g. pericarditis, in other conditions, including coronary artery disease and heart failure, which are associated with a chronic low-grade inflammatory state, the evidence regarding its potential use remains sparse. In this concise review, we present key features of this drug and the rationale for colchicine therapy, in the context of acute and chronic coronary artery disease, as well as in ischemic heart failure and critically examine the evidence concerning a possible future role of colchicine treatment in these conditions.
Teaching an Old Dog New Tricks: Colchicine in Cardiovascular Medicine. [2018]Colchicine is one of the oldest known drugs that remains part of the current pharmacopeia. Recent studies have examined the efficacy of colchicine in cardiology with promising results. We conducted a search of electronic databases for studies on colchicine in cardiovascular medicine published through October 2016. As the utilization of colchicine in the management of cardiac conditions grows, it is paramount that internists and cardiologists are familiarized with its benefits and risks. We present a comprehensive review of the role of colchicine in the management of cardiovascular diseases with a strong emphasis on side effects and potential drug interactions.
Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. [2022]Colchicine is effective for the treatment of acute pericarditis and first recurrences. However, conclusive data are lacking for the efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis.
Colchicine and the heart. [2021]Colchicine is a unique, sophisticated anti-inflammatory agent that has been used for decades for the prevention of acute inflammatory flares in gout and familial Mediterranean fever. In recent years, clinical trials have demonstrated its potential in a range of cardiovascular (CV) conditions. Colchicine is avidly taken up by leucocytes, and its ability to bind to tubulin and interfere with microtubular function affects the expression of cytokines and interleukins, and the ability of neutrophils to marginate, ingress, aggregate, express superoxide, release neutrophil extracellular traps, and interact with platelets. In patients with acute and recurrent pericarditis, clinical trials in >1600 patients have consistently shown that colchicine halves the risk of recurrence [relative risk (RR) 0.50, 95% confidence interval (CI) 0.42-0.60]. In patients with acute and chronic coronary syndromes, multicentre randomized controlled trials in >11 000 patients followed for up to 5 years demonstrated that colchicine may reduce the risk of CV death, myocardial infarction, ischaemic stroke and ischaemia-driven revascularization by >30% (RR 0.63, 95% CI 0.49-0.81). The use of colchicine at doses of 0.5-1.0 mg daily in CV trials has proved safe. Early gastrointestinal intolerance limits its use in ∼10% of patients; however, ∼90% of patients tolerate it well over the long term. Despite isolated case reports, clinically relevant drug interactions with moderate to strong CYP3A4 inhibitors/competitors or P-glycoprotein inhibitors/competitors are rare if this dosage of colchicine is used in the absence of advanced renal or liver disease. The aim of this review is to summarize the contemporary data supporting the efficacy and safety of colchicine in patients with CV disease.