Colchicine in Acutely Decompensated HFREF

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.

Conditions

Heart Failure, Decompensated Heart Failure, Heart Failure With Reduced Ejection Fraction

Study Overview

Study Details

Study overview

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.

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

Colchicine in Acutely Decompensated HFREF

Condition
Heart Failure
Intervention / Treatment

-

Contacts and Locations

Charlottesville

UVA Health, Charlottesville, Virginia, United States, 22908

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

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

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Virginia,

Antonio Abbate, MD, PRINCIPAL_INVESTIGATOR, UVA Health

Study Record Dates

2028-06