Clinical trial NCT04500665: Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine
Official title: Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Diseases
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2020-08-05
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Between-group change in left ventricular global longitudinal strain
timeFrame: 4 weeks
Secondary outcomes:
measure: Between-group change in left ventricular systolic and diastolic function
timeFrame: 4 weeks
measure: Between-group change in left ventricular volumes
timeFrame: 4 weeks
measure: Between-group change in left ventricular size
timeFrame: 4 weeks
measure: Between-group change in systemic inflammation
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Leo F Buckley, PharmD MPH
role: PRINCIPAL_INVESTIGATOR
References: