Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine

Study Overview
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Brief Summary
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This study is designed to determine the efficacy and safety of colchicine in patients with chronic kidney disease.

Official Title
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Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Drug: Colchicine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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A. Inclusion Criteria: Age 21 years to 80 years eGFR of 15 to 75 mL/min per 1.73 m2 Urine albumin-to-creatinine ratio of 200 mg/g or greater Serum high-sensitivity C-reactive protein concentration of greater than 2 mg/L within 2 weeks of screening Reduction in high-sensitivity C-reactive protein concentration of 25% or greater during the open-label run-in phase Left ventricular global longitudinal strain of -16% or worse within the past 12 months Use of maximally tolerated doses of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker if urine albumin-to-creatinine ratio greater than 300 mg-g Use of a sodium-glucose co-transporter-2 inhibitor if indicated in the opinion of the participant's primary clinician Willing and able to provide written informed consent and to adhere to the study protocol B. Exclusion Criteria: History of intolerance or allergy to colchicine Hospitalization for any reason within the previous 30 days Acute condition that requires emergent treatment in the opinion of a physician investigator Stage C or D heart failure according to ACC-AHA criteria77 Left ventricular ejection fraction less than 40% Prior acute coronary syndrome Symptomatic valvular heart disease Congenital heart disease (corrected or uncorrected) History of orthotopic heart transplant Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg Kidney failure, defined as kidney transplant recipient or requirement for hemodialysis or peritoneal dialysis Worsening kidney function or acute kidney injury, defined as an increase in serum creatinine of greater than 0.3 mg/dL in the previous 30 days or 50% within the previous 7 days Use of immunosuppressive or anti-inflammatory medications within the previous 30 days, with the exception of less than 5 days of non-steroidal anti-inflammatory drugs or corticosteroids for acute pain or other acute conditions that have since fully resolved provided that the last dose of non-steroid anti-inflammatory drug was at least 7 days before enrollment Diagnosis of rheumatoid arthritis, systemic lupus erythematosus, other systemic auto-immune or auto-inflammatory condition Familial Mediterranean Fever, gout (unless no flare within the previous 12 months), pericarditis or other indications for colchicine treatment Use of systemic antimicrobial therapy within the previous 30 days or active infection History of respiratory illness that, in the opinion of a physician investigator, may increase the risk of pneumonia Surgery within the previous 30 days or surgery planned to occur within the expected study period Current malignancy or receipt of treatment for malignancy within the previous 1 year Frailty or life-expectancy shortened by comorbidity such as cancer that would increase the participant's risk in the opinion of a physician investigator Neutrophil count < 2,000 cells/mm3 Platelet count < 50,000 cells/mm3 Concomitant use of a P-gp inhibitor (e.g., cyclosporine, ranolazine, digoxin) and/or moderate-strong CYP3A4 inhibitor (e.g., clarithromycin, indinavir, itraconazole, ritonavir, nefazodone, diltiazem, verapamil, grapefruit juice, fluconazole) Medications that may cause myopathy or rhabdomyolysis (i.e., simvastatin, gemfibrozil, fenofibrate) , a creatine kinase level after the run-in period that exceeds the upper limit of the normal laboratory reference range (if baseline was below the upper limit) or that increases by 50% or more from pre- to post-run-in Moderate-severe hepatic disease (Child-Pugh B or C) Pregnant or unwilling/unable to assure appropriate contraception Breastfeeding

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine<br>Colchicine 0.3 mg once daily | Drug: Colchicine<br>* Colchicine<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group change in left ventricular global longitudinal strain | Assessed using transthoracic echocardiography | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group change in left ventricular systolic and diastolic function | Assessed using transthoracic echocardiography | 4 weeks | 
| Between-group change in left ventricular volumes | Assessed using transthoracic echocardiography | 4 weeks | 
| Between-group change in left ventricular size | Assessed using transthoracic echocardiography | 4 weeks | 
| Between-group change in systemic inflammation | Assessed using C-reactive protein | 4 weeks |