NCT06286423 · University of Virginia
Colchicine in Acutely Decompensated HFREF
What this study is about
This is a double blind, compared against an inactive treatment 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 randomly assigned 1:1 to receive either the experimental drug (Colchicine) or matching placebo.
View original scientific description
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.
Interventions
DRUG
Colchicine 0.6 mg
Colchicine treated subjects will take 0.6mg of drug 2x per day (1 time if kidney disease is present) for 14 days, then will take 0.6mg of drug 1x per day (or every other day if kidney disease is present) for 76 +/1 days.
DRUG
Control/Placebo group
Placebo treated subjects will take 0.6mg of placebo 2x per day (1 time if kidney disease is present) for 14 days, then will take 0.6mg of placebo1x per day (or every other day if kidney disease is present) for 76 +/1 days.
Primary outcome measures
Difference in the change in high sensitivity C-reactive protein (hsCRP) between colchicine arm and placebo arm in the first 72 hours of treatment
Time frame: Baseline to 72 hours
Change in plasma concentration of hsCRP between baseline and after 72 hours after treatment initiation, comparing colchicine arm vs placebo
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Primary admission diagnosis of acute decompensated heart failure as evidenced by:
- Heart failure symptoms and at least one of the following:
- Pulmonary congestion/edema at physical exam (or chest radiography)
- E/e' \> 13 on transthoracic echocardiography
- Left heart catheterization showing elevated left ventricular (LV) end-diastolic pressure \>18 mmHg or right heart catheterization showing pulmonary artery occluding pressure (wedge) \>16 mmHg
- Elevated plasma B-type natriuretic peptide (\>100 pg/ml) or N-terminal B-type natriuretic peptide (\>300 pg/ml)
- LV systolic dysfunction (left ventricular ejection fraction \[LVEF\] \<40%) during the index hospitalization or prior 12 months;
- Expected duration of heart failure at least three months
- Age 18 years or older
- 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
Exclusion criteria
- Concomitant clinically significant comorbidities that would interfere with the execution or interpretation of the study, including but not limited to acute coronary syndromes, uncontrolled hypertension or orthostatic hypotension, tachy- or brady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disorders affecting respiration
- Cardiac resynchronization therapy (CRT), coronary artery revascularization procedures, or heart valve surgeries performed within 3 months or planned during the admission
- Previous or planned implantation of left ventricular assist devices or heart transplantation
- Chronic use of intravenous inotropes
- Current or recent (i.e. within 4 half-lives) use of immunosuppressive or anti-inflammatory drugs (not including NSAIDs).
- Current treatment with colchicine or planned initiation of colchicine therapy in the next three months for gout
- Chronic inflammatory disorder, including but not limited to rheumatoid arthritis and systemic lupus erythematosus
- Active infection (of any type)
- Chronic or recurrent infectious disease, including hepatitis B virus, hepatitis C virus, and HIV/AIDS
- Prior (within the past 5 years) or current malignancy, with the exclusion of in situ lesion with low potential for progression
- Any comorbidity leading to expected survival less than three months or inability to complete the study
- End-stage kidney disease requiring renal replacement therapy
- Neutropenia (\<2,000/mm3) or Thrombocytopenia (\<50,000/mm3)
- For all biological females with child bearing potential a pregnancy test will be performed as part of standard of care.
- Presence of specific contraindications to colchicine treatment, which may include
- Previous adverse reaction to colchicine
- Biliary obstruction
- Renal impairment with estimated glomerular filtration rate (eGFR) \<30 ml/min
- Liver cirrhosis from stage Child-Pugh A to more advanced
- Treatment with medication contraindicated for concomitant use with colchicine per Food and Drugs Administration labeling, including:
- Protease inhibitors
- Macrolides antibiotic
- Ketoconazole, Fluconazole and Itraconazole
- Non-dihydropiridine calcium channel blockers
- Cyclosporine
Where
- Charlottesville, Virginia
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 8, 2024 · Source of record for eligibility and locations