Chronic Kidney Diseases
Conditions
Brief summary
This study is designed to determine the efficacy and safety of colchicine in patients with chronic kidney disease.
Interventions
DRUGColchicine
Colchicine
DRUGPlacebo
Placebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
A. Inclusion Criteria: * Age 21 years to 80 years (inclusive) * eGFR of 15 to 75 mL/min per 1.73 m2 * Urine albumin-to-creatinine ratio of greater than 30 mg/g * 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
1. History of intolerance or allergy to colchicine 2. Hospitalization for any reason within the previous 30 days 3. Acute condition that requires emergent treatment in the opinion of a physician investigator 4. Stage C or D heart failure according to ACC-AHA criteria77 5. Left ventricular ejection fraction less than 40% 6. Symptomatic valvular heart disease 7. Congenital heart disease (corrected or uncorrected) 8. History of orthotopic heart transplant 9. Kidney failure, defined as kidney transplant recipient or requirement for hemodialysis or peritoneal dialysis 10. 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 11. 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 12. Familial Mediterranean Fever, gout (unless no flare within the previous 12 months), pericarditis or other indications for colchicine treatment 13. Use of systemic antimicrobial therapy within the previous 30 days or active infection 14. History of respiratory illness that, in the opinion of a physician investigator, may increase the risk of pneumonia 15. Surgery within the previous 30 days or surgery planned to occur within the expected study period 16. Current malignancy or receipt of treatment for malignancy within the previous 1 year 17. Frailty or life-expectancy shortened by comorbidity such as cancer that would increase the participant's risk in the opinion of a physician investigator 18. Neutrophil count \< 2,000 cells/mm3 19. Platelet count \< 50,000 cells/mm3 20. 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) 21. 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 22. Moderate-severe hepatic disease (Child-Pugh B or C) 23. Pregnant or unwilling/unable to assure appropriate contraception 24. Breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Between-group change in left ventricular global longitudinal strain | 4 weeks | Assessed using transthoracic echocardiography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Between-group change in left ventricular systolic and diastolic function | 4 weeks | Assessed using transthoracic echocardiography |
| Between-group change in left ventricular volumes | 4 weeks | Assessed using transthoracic echocardiography |
| Between-group change in left ventricular size | 4 weeks | Assessed using transthoracic echocardiography |
| Between-group change in systemic inflammation | 4 weeks | Assessed using C-reactive protein |
Countries
United States
Contacts
Primary ContactLeo F Buckley, PharmD MPH
Outcome results
None listed