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

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