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

Официальное название

The Effect of ColcHicine on the Incidence of Knee or Hip Replacements: a Randomized, Double-blind, Multicentre Study in Symptomatic Knee or Hip Osteoarthritis

Обзор

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

Вмешательства

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

Первичные конечные точки

• Time to first knee or hip replacement [Срок оценки: 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]

Вторичные конечные точки (11)

• Course of pain as assessed by NRS (numeric rating scale) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Sint Maartenskliniek — Nijmegen

Публикации

• 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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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