Using colchicine to treat acutely decompensated heart failure with reduced ejection fraction

Colchicine in Acutely Decompensated Heart Failure With Reduced Ejection Fraction: a Pilot Study

This study is testing if colchicine, an anti-inflammatory medication, can help people in the hospital with heart failure feel better and improve their heart function.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Virginia (other)
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT06286423 on ClinicalTrials.gov

What this trial studies

This pilot trial investigates the effects of colchicine, an anti-inflammatory medication, on patients hospitalized with acutely decompensated heart failure and inflammation. Participants will be randomly assigned to receive either colchicine or a placebo for a total of 90 days, with a specific dosing regimen. The study aims to assess the safety and efficacy of colchicine in reducing inflammation and improving heart function in this patient population. The trial will monitor for adverse effects and adjust dosages as necessary based on kidney function and gastrointestinal symptoms.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a primary diagnosis of acute decompensated heart failure and evidence of inflammation.

Not a fit: Patients with conditions that contraindicate the use of colchicine or those with severe renal impairment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from acutely decompensated heart failure with reduced ejection fraction.

How similar studies have performed: Previous studies have shown positive effects of colchicine in other cardiovascular conditions, suggesting potential for success in this novel application.

Eligibility criteria

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

Where this trial is running

Charlottesville, Virginia

• UVA Health — Charlottesville, Virginia, United States (RECRUITING)

Study contacts

• Principal investigator: Antonio Abbate, MD — UVA Health
• Study coordinator: Austin Hogwood

Conditions: Heart Failure, Decompensated Heart Failure, Heart Failure With Reduced Ejection Fraction, Colchicine, Heart Failure with Reduced Ejection Fraction, HFrEF