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

Overview

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

Interventions

• Drug Colchicine
  Colchicine 0.5mg tablets once a day for 3 to 4.5 years
• Drug Placebo
  Placebo tablets once a day for 3 to 4.5 years

Primary outcome measures

• Time to first knee or hip replacement [Time frame: 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 (11)

• Course of pain as assessed by NRS (numeric rating scale) [Time frame: 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]
• Course of pain as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index) [Time frame: 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]
• Course of physical function as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index) [Time frame: 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]
• Course of joint space narrowing on X-ray [Time frame: 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 [Time frame: 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) [Time frame: 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 with clinical or radiological onset of OA in new joint group other than present at baseline over the trial period [Time frame: 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 [Time frame: 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) [Time frame: 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 [Time frame: 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 [Time frame: 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]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Sint Maartenskliniek — Nijmegen

Publications

• Heijman MWJ, van den Ende CHM, Cornel JH, Smolders JMH, Schers HJ, Kievit W, Koeter S, van den Bemt BJF, Popa CD. Design of a randomised, placebo-controlled, double-blind multicentre study assessing the effect of colchicine on the incidence of knee or hip replacements in symptomatic knee or hip osteoarthritis: the ECHO trial. BMJ Open. 2025 Apr 14;15(4):e098096. doi: 10.1136/bmjopen-2024-098096. PMID 40228852

Identifiers

NCT: NCT06578182 · SMaartenskliniek · 10140262210012 · 2024-511359-16-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗