Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine

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

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Drug: Placebo; Drug: Colchicine

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Leo F Buckley, PharmD MPH; Phone Number: 617-732-5500; Email: lfbuckley@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Leo Buckley, PharmD; Phone Number: 617-732-4497; Email: lfbuckley@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

A. Inclusion Criteria:

1. Age 21 years to 80 years (inclusive)
2. eGFR of 15 to 75 mL/min per 1.73 m2
3. Urine albumin-to-creatinine ratio of greater than 30 mg/g

7. 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 8. Use of a sodium-glucose co-transporter-2 inhibitor if indicated in the opinion of the participant's primary clinician 9. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo once daily	Drug: Placebo; Placebo
Experimental: Colchicine; Colchicine 0.3 mg once daily	Drug: Colchicine; Colchicine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Leo F Buckley, PharmD MPH, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): November 11, 2026

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Cardiomyopathies; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 2020P002468; K23HL150311 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes