Clinical trial NCT06203977: Inflammation REduction to Prevent cArdiovascular Injury in Renal Disease (REPAIR)
Official title: Inflammation REduction to Prevent cArdiovascular Injury in Renal Disease (REPAIR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Kidney Diseases
Renal Failure
Keywords: Tolerance
Colchicine Resistance
Hematologic markers
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
Collaborators: name: Hamilton Academic Health Sciences Organization
name: St. Joseph's Health Care London
First posted: 2024-01-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1 basket trial including 2 open-label single-arm cohorts: REPAIR CKD cohort and REPAIR Dialysis cohort
Primary purpose: PREVENTION

Brief summary: Phase 1 basket trial including 2 open-label single-arm cohorts: REPAIR CKD cohort and REPAIR Dialysis cohort. Open label colchicine 0.3 mg daily for 8 weeks followed, in patients who tolerated the 0.3 mg dose, by forced titration to 0.6 mg daily for 8 weeks.

Detailed description: The REPAIR CKD cohort will enroll 100 patients with chronic kidney disease not requiring dialysis. The REPAIR Dialysis cohort will enroll 100 patients with chronic kidney disease requiring chronic maintenance dialysis. Each participant will be followed for up to 17 weeks, to determine among adults with severe chronic kidney disease not requiring dialysis and (separately) in those requiring dialysis, the proportion who, over 8 weeks of treatment, discontinue colchicine 1) 0.3 mg daily and 2) 0.6 mg daily.

Eligibility criteria: Inclusion Criteria:

1. One of either:

   1.2 Estimated GFR using CKD-EPI 2021 equation of ≤30 ml/min/1.73m2 on at least two occasions separated by at least 2 months and do not yet require dialysis and are not expected by their treating nephrologist to require dialysis in the next 6 months (REPAIR CKD cohort), or 1.3 receiving chronic maintenance dialysis 2 or more times per week for the previous 90 days (REPAIR Dialysis cohort);
2. Age ≥18 years
3. Provide informed consent to participate.

Exclusion Criteria:

1. Currently treated with and cannot withdraw colchicine due to medical necessity; or
2. Known allergy/sensitivity to colchicine; or
3. Prior self-reported intolerance to colchicine at a dose of 0.6 mg daily or lower; or
4. Currently pregnant or planning to become pregnant or breastfeed during the study; or
5. Of childbearing potential AND do not have a negative pregnancy test OR do not agree to use two forms of contraception for the duration of the study; or
6. Anticipated living donor renal transplant within the next 6 months; or
7. Using a strong inhibitor of p-glycoprotein or strong inhibitor of CYP3A4 in the last 14 days; or
8. B12 deficiency not managed with intramuscular supplementation; or
9. Uncontrolled chronic diarrhea; or
10. Cirrhosis, or chronic active hepatitis; or
11. Pre-existent neuromuscular disease or persistent serum CK level \> 3 times the upper limit of normal as measured within the past 60 days and determined to be non-transient through repeat testing; or
12. Patient with any of the following within the past 60 days:

    * white blood cell count \< 3.0 X 109/L; or
    * platelet count \<110 X 109/L; or
    * ALT or AST \> 3 times the upper limit of normal (ULN); or
    * total bilirubin \> 2 times ULN and not due to Gilbert syndrome.
13. Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Primary outcomes:
measure: Dose tolerance
timeFrame: Up to 17 weeks
measure: Early discontinuations
timeFrame: Up to 17 weeks
Secondary outcomes:
measure: Reason for drug discontinuation
timeFrame: Up to 17 weeks
measure: Drug adherence
timeFrame: Up to 17 weeks
measure: Major Side Effects
timeFrame: Up to 17 weeks
Other outcomes:
measure: Colchicine Concentration
timeFrame: Up to 17 weeks
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: McMaster University
name: Michael Walsh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: