The Effect of ColcHicine on the Incidence of Knee or Hip Replacements

Phase 3

Recruiting

• Conditions: Osteoarthritis, Knee; Osteoarthritis, Hip
• Interventions: Drug: Colchicine; Drug: Placebo

• Registration Number: NCT06578182
• Lead Sponsor: Sint Maartenskliniek

Brief Summary

The goal of this clinical trial is to evaluate the effect of treatment with colchicine 0.5mg once daily as compared to placebo in patients with knee or hip osteoarthritis on the incidence of first occurrence of knee or hip replacement. The main question it aims to answer is:

Does colchicine lower the number of knee or hip replacements in participants with osteoarthritis?

Researchers will compare colchicine to a placebo (a look-alike substance that contains no drug) to see if colchicine works to treat osteoarthritis.

Participants will:

* take colchicine every day for 3 tot 4.5 years

* visit the clinic every year for check-up and tests such as blood samples and x-rays

* fill in questionnaires every 3 months

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-04
• Study First Submitted QC: 2024-08-27
• Study First Posted: 2024-08-29
• Status Verified: 2024-12
• Study Start: 2025-01-01
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-20
• Primary Completion: 2029-03-31
• Study Completion: 2029-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1410

Inclusion Criteria

• clinical diagnosis of knee or hip OA
• 45 ≤ age ≤ 80 (upper age limit is similar to that in the LoDoCo2 trial and takes in consideration the lower number of joint replacements in people older than 80 years)
• documented radiographic changes typical for advanced knee/hip OA (Kellgren & Lawrence score ≥ 2), or at least 2-year history of complaints due to OA in the hip and/or knee

Exclusion Criteria

• On a waiting list for primary joint replacement surgery of the hip or knee, irrespective of cause
• Any absolute contraindication for knee or hip replacement in the future
• More than one previous hip or knee replacements
• Other known medical disease that may affect joints
• Known generalized pain syndromes such as fibromyalgia
• Renal impairment as evidenced by serum creatinine >150µmol/l or estimated glomerular filtration rate (eGFR) <50mL/min/1.73m2
• Liver function impairment as evidenced by serum alanine transferase (ALAT) > 3 ULN (upper limit of normal)
• Blood dyscrasia
• High frailty (clinical frailty scale ≥ 7) or predicted life expectancy < 5 years
• Peripheral neuritis, myositis or marked myo-sensitivity to statins
• Current use of colchicine for another indication
• Intolerance to colchicine
• use of macrolide antibiotics (i.e. clarithromycin, erythromycin, azithromycin), antimycotics (i.e. ketoconazole, itraconazole and voriconazole), protease inhibitors & anti-retroviral drugs (i.e. ritonavir, lopinavir, tipranavir, atazanavir, darunavir, indinavir, saquinavir, and cobicistat), anti-arrhythmic drugs (i.e. verapamil, diltiazem), or immunosuppressant (i.e. cyclosporine)
• Current enrollment in another trial
• Incapacitated patients
• Pregnant or breastfeeding female
• Fertile female participants not taking sufficient anti-conception
• Male participants unwilling to use effective contraception during the study to prevent pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine	Colchicine	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Time to first knee or hip replacement	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

Secondary Outcome Measures

Name	Time	Method
Course of pain as assessed by NRS (numeric rating scale)	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years	The 11-point NRS ranges from '0' ("no pain") to '10' ("worst pain imaginable")
Course of pain as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index)	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years	5 items are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). Higher scores indicate more pain
Course of physical function as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index)	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years	17 items are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). Higher scores indicate more functional limitations
Course of joint space narrowing on X-ray	From baseline until the date of first documented knee or hip replacement or study end, whichever comes first, assessed up to 4.5 years
Course of low-grade inflammation as assessed by hs-CRP	At enrolment, at baseline, 1 year thereafter, and at study completion (approximately 4.5 years)
Course of quality of life as assessed by EQ-5D-5L (European Quality of Life 5 Dimensions)	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years	The EQ-5D-5L comprises 5 dimensions with each dimension having 5 response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), unable to/extreme problems (5). EQ-5D-5L health states can be represented by a single summary number (index value) (range -0.624 to 1.000). Higher scores equals better quality of life
Number of participants with clinical or radiological onset of OA in new joint group other than present at baseline over the trial period	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years
Time to clinical or radiological onset of OA in new joint group other than present at baseline over the trial period	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years
Number of participants using pain medication during the study registered per drug type (e.g. paracetamol, NSAIDs, opioids)	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years
Onset of new cardiovascular events, defined as myocardial infarction, peripheral artery disease, ischemia-driven coronary revascularization, ischemic stroke, or cardiovascular death	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years
Direct and indirect costs related to treatment and disease burden due osteoarthritis	From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

Trial Locations

Locations (1)

Sint Maartenskliniek; 🇳🇱 Nijmegen, Netherlands