Clinical trial NCT06578182: The Effect of ColcHicine on the Incidence of Knee or Hip Replacements
Official title: The Effect of ColcHicine on the Incidence of Knee or Hip Replacements: a Randomized, Double-blind, Multicentre Study in Symptomatic Knee or Hip Osteoarthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Keywords: Colchicine
Knee replacement
Hip replacement
Lead sponsor: Sint Maartenskliniek
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: RSMK
name: Tiofarma
name: Dutch Arthritis Foundation Reuma Nederland
First posted: 2024-08-29
Enrollment: 1410
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Time to first knee or hip replacement
timeFrame: 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 outcomes:
measure: Course of pain as assessed by NRS (numeric rating scale)
timeFrame: 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
measure: Course of pain as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index)
timeFrame: 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
measure: Course of physical function as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index)
timeFrame: 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
measure: Course of joint space narrowing on X-ray
timeFrame: From baseline until the date of first documented knee or hip replacement or study end, whichever comes first, assessed up to 4.5 years
measure: Course of low-grade inflammation as assessed by hs-CRP
timeFrame: At enrolment, at baseline, 1 year thereafter, and at study completion (approximately 4.5 years)
measure: Course of quality of life as assessed by EQ-5D-5L (European Quality of Life 5 Dimensions)
timeFrame: 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
measure: Number of participants with clinical or radiological onset of OA in new joint group other than present at baseline over the trial period
timeFrame: 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
measure: Time to clinical or radiological onset of OA in new joint group other than present at baseline over the trial period
timeFrame: 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
measure: Number of participants using pain medication during the study registered per drug type (e.g. paracetamol, NSAIDs, opioids)
timeFrame: 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
measure: Onset of new cardiovascular events, defined as myocardial infarction, peripheral artery disease, ischemia-driven coronary revascularization, ischemic stroke, or cardiovascular death
timeFrame: 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
measure: Direct and indirect costs related to treatment and disease burden due osteoarthritis
timeFrame: 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
Other outcomes:
measure: The number of (serious) adverse events
timeFrame: 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
measure: The number of withdrawals due to (serious) adverse events
timeFrame: 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
measure: Changes in laboratory data (i.e. serum creatinine, estimated glomerular filtration rate, and alanine transferase)
timeFrame: At enrolment, at baseline, 1 year thereafter, and at study completion (approximately 4.5 years)
Locations:
city: Nijmegen
country: Netherlands
facility: Sint Maartenskliniek
Study officials:
References: