Recruiting

Colchicine

Sponsor:

University of Virginia

Code:

NCT06286423

Conditions

Heart Failure

Decompensated Heart Failure

Heart Failure With Reduced Ejection Fraction

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Colchicine 0.6 mg

Control/Placebo group

Study Details

Brief summary:

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.

Conditions

Heart Failure

Decompensated Heart Failure

Heart Failure With Reduced Ejection Fraction

Study ID

NCT06286423

Start date

Jun, 2024

Status verified date

May, 2024

Completion date

Jun, 2028

Anticipated

Primary completion date

Jun, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. 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)
2. LV systolic dysfunction (left ventricular ejection fraction \[LVEF\] <40%) during the index hospitalization or prior 12 months;
3. Expected duration of heart failure at least three months
4. Age 18 years or older
5. Willing and able to provide written informed consent
6. Screening plasma CRP >0.3 mg/dL (3 mg/L) or high-sensitivity CRP >2 mg/L

Exclusion Criteria:

1. 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
2. Cardiac resynchronization therapy (CRT), coronary artery revascularization procedures, or heart valve surgeries performed within 3 months or planned during the admission
3. Previous or planned implantation of left ventricular assist devices or heart transplantation
4. Chronic use of intravenous inotropes
5. Current or recent (i.e. within 4 half-lives) use of immunosuppressive or anti-inflammatory drugs (not including NSAIDs).
6. Current treatment with colchicine or planned initiation of colchicine therapy in the next three months for gout
7. Chronic inflammatory disorder, including but not limited to rheumatoid arthritis and systemic lupus erythematosus
8. Active infection (of any type)
9. Chronic or recurrent infectious disease, including hepatitis B virus, hepatitis C virus, and HIV/AIDS
10. Prior (within the past 5 years) or current malignancy, with the exclusion of in situ lesion with low potential for progression
11. Any comorbidity leading to expected survival less than three months or inability to complete the study
12. End-stage kidney disease requiring renal replacement therapy
13. Neutropenia (<2,000/mm3) or Thrombocytopenia (<50,000/mm3)
14. Pregnancy

  • For all biological females with child bearing potential a pregnancy test will be performed as part of standard of care.
15. 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
16. Prisoners
17. Treatment with medication contraindicated for concomitant use with colchicine per

Food and Drugs Administration labeling, including:

  • Protease inhibitors
  • Macrolides antibiotic
  • Ketoconazole, Fluconazole and Itraconazole
  • Nefazodone
  • Non-dihydropiridine calcium channel blockers
  • Aprepitant
  • Ranolazine
  • Cyclosporine

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Colchicine 0.6 mg treatment group

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).

placebo comparator: Control/Placebo group

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).

Interventions

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.

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 measure

  • 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 ]

Central Contacts and Locations

Central contacts

Locations

UVA Health

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Austin Hogwood

ach2jb@virginia.edu

Francesco Moroni, MD

nmf7mm@uvahealth.org

Principal Investigator:

Antonio Abbate, MD

More Information

Sponsor

University of Virginia

Last update posted

May 8, 2024

Last verified

May, 2024

Keywords

  • Colchicine
  • Heart Failure
  • Decompensated Heart Failure
  • Heart Failure with Reduced Ejection Fraction
  • HFrEF

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2024-05-08.