Colchicine in Acutely Decompensated HFREF
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Virginia
About 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Colchicine 0.6 mg
DrugColchicine 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
DrugPlacebo 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.
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: Colchicine 0.6 mg treatment groupExperimental treatment 1 intervention
Group B: Control/Placebo groupPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Difference in the change in high sensitivity C-reactive protein (hsCRP) between colchicine arm and placebo arm in the first 72 hours of treatment
Change in plasma concentration of hsCRP between baseline and after 72 hours after treatment initiation, comparing colchicine arm vs placebo
Time frame
Baseline to 72 hoursSecondary outcomes
1
Difference in hsCRP area under curve between colchicine and placebo arm at 14 days
Area under curve of hsCRP measurements obtained at baseline, 24h, 48h, 72h and 14 days, comparing colchicine vs placebo
Time frame
Baseline to 14 days2
Difference in change in plasma IL-6 concentration between colchicine arm and placebo arm in the first 72 hours of treatment
Change in plasma concentration of IL-6 between baseline and after 72 hours after treatment initiation, comparing colchicine arm vs placebo
Time frame
Baseline to 72 hoursOther outcomes
1
Difference in the incidence of a composite of all-cause mortality or hospitalizations for heart failure at 90 days
Occurrence of death or heart failure hospitalization during trial participation, comparing colchicine and placebo arms
Time frame
Baseline to 90 daysSponsors and contacts
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Source ClinicalTrials.gov