Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine

• Status: Not yet recruiting
• Trial end date: 2025-11-11
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Colchicine

Criteria

A. Inclusion Criteria:

1. Age 21 years or older

2. One of either (a) OR (b):

1. Severely decreased eGFR with or without albuminuria76: 15 to 29 mL/min per 1.73 m2 (using the serum creatinine-based CKD-EPI equation)

2. Moderately decreased eGFR and severely increased albuminuria76: 30-44 mL/min per 1.73 m2 (using the serum creatinine-based CKD-EPI equation) and urine albumin-to-creatinine ratio of greater than 300 mg-g; early morning urine sample is preferred but a random spot urine sample is acceptable

3. Serum high-sensitivity C-reactive protein concentration of greater than 2 mg/L within 2 weeks of screening

4. Reduction in high-sensitivity C-reactive protein concentration of 25% or greater during the open-label run-in phase

5. Left ventricular global longitudinal strain of -16% or worse within the past 12 months

6. 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

7. If hemoglobin A1c of 6.5% to 12.0% and urine albumin-to-creatinine ratio greater than 300 mg-g, use of canagliflozin 100 mg daily as tolerated

8. Willing and able to provide written informed consent and to adhere to the study protocol

B. Exclusion Criteria:

1. Hospitalization for any reason with the previous 30 days

2. Acute condition that requires emergent treatment

3. Stage C or D heart failure according to ACC-AHA criteria

4. Prior acute coronary syndrome

5. Symptomatic valvular heart disease

6. Congenital heart disease (corrected or uncorrected)

7. History of orthotopic heart transplant

8. Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg

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. Diagnosis of rheumatoid arthritis, systemic lupus erythematosus, other systemic auto-immune or auto-inflammatory condition

13. Familial Mediterranean Fever, gout, pericarditis or other indications for colchicine treatment

14. Use of systemic antimicrobial therapy within the previous 30 days or active infection

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. Neutrophil count < 2,000 cells/mm3

18. Platelet count < 50,000 cells/mm3

19. 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)

20. Medications that may cause myopathy or rhabdomyolysis (e.g., simvastatin, gemfibrozil, fenofibrate)

21. Moderate-severe hepatic disease (Child-Pugh B or C)

22. Pregnant or unwilling/unable to assure appropriate contraception

23. Breastfeeding