Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine

Launched by BRIGHAM AND WOMEN'S HOSPITAL · Aug 4, 2020

Keywords

ClinConnect Summary

This clinical trial is studying the use of a medication called colchicine to see if it can help people with chronic kidney disease who also have heart problems known as uremic cardiomyopathy. The goal is to find out whether colchicine is both safe and effective for these patients. The trial is currently looking for participants between the ages of 21 and 80 who have specific kidney function levels and are already using certain heart medications.

To join the study, participants need to be in reasonably good health and meet other criteria, such as having a certain level of kidney function and being able to provide consent. Those with a history of allergies to colchicine, recent hospitalizations, or certain heart conditions may not be eligible. If you decide to participate, you will be closely monitored throughout the study, and your health will be checked regularly to ensure your safety. This trial could provide valuable information that may help improve treatment options for people with chronic kidney disease in the future.

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Eligibility 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