Evaluation of Colchicine on the Incidence of Knee or Hip Replacements in Patients with Symptomatic Osteoarthritis: A Randomized, Double-Blind, Multicenter Study

The primary objective of this study is to evaluate the effect of treatment with **colchicine** 0.5mg once daily compared to placebo on the incidence of the first occurrence of knee or hip replacement in patients with knee or hip **osteoarthritis**. This is clinically relevant as it aims to determine whether colchicine can delay or prevent the need for joint replacement surgery, which is a significant intervention for patients with advanced osteoarthritis.

Secondary objectives include evaluating the effect of colchicine on:

• Pain management in patients with knee or hip osteoarthritis.
• Physical functioning of the affected individuals.
• Radiologic progression of the disease.
• Low-grade inflammation associated with osteoarthritis.
• Quality of life of the patients.
• Incidence of new osteoarthritis diagnosis in other joint groups.
• Use of pain medication by the patients.
• Occurrence of cardiovascular events.
• Direct and indirect costs related to treatment and disease burden.

The clinical trial focuses on patients diagnosed with **osteoarthritis** of the knee or hip, aiming to assess the impact of colchicine treatment compared to a placebo on the incidence of joint replacement. The study population includes both male and female participants aged between 45 and 80 years. Participants are required to have a clinical diagnosis of knee or hip osteoarthritis, with documented radiographic changes typical for advanced stages of the condition or a history of related complaints for at least two years. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the effect of **colchicine** 0.5 mg once daily compared to a placebo in patients with knee or hip **osteoarthritis** (OA) on the incidence of first occurrence of knee or hip replacement. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is expected to commence recruitment on October 1, 2024, and conclude by April 30, 2029, with an estimated duration of approximately five years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a clinical diagnosis of knee or hip OA, age between 45 and 80 years, and documented radiographic changes typical for advanced OA. Following randomization, participants will attend regular follow-up visits to monitor the course of pain, physical function, radiological progression, and quality of life over the trial period. Additionally, changes in low-grade inflammation will be assessed at one year and at the end of the study. The primary endpoint is the time from randomization to the first incident of total knee replacement (TKR) or total hip replacement (THR).

Secondary endpoints include the onset of new cardiovascular events, use of pain medication, and direct and indirect costs related to treatment and disease burden due to osteoarthritis. Participants are expected to be involved in the study for the entire trial duration unless conditions arise that necessitate early termination, such as adverse events or withdrawal of consent. The trial aims to provide comprehensive data on the efficacy and safety of colchicine in reducing the need for joint replacement surgeries in patients with symptomatic knee or hip osteoarthritis.

The clinical trial involves the administration of **Colchicine Tiofarma 500 microgram Tablets** as the experimental medication. The pharmaceutical form of this medication is a tablet, and it contains the active substance **colchicine**. The tablets are administered orally. The dosage regimen for this trial is 0.5 mg of colchicine once daily, with a maximum total daily dose of 1.5 mg. The treatment period is set for a maximum of 60 days. The medication is manufactured by TIOFARMA BV and is identified by the marketing authorization number PL 17299/0003. The ATC code for colchicine is M04AC01, indicating its classification as a medication used in the treatment of gout.

The study also includes a **placebo** as a non-experimental treatment to serve as a comparator. The placebo is designed to match the experimental medication in appearance and is administered in the same oral route and frequency as the colchicine tablets. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias. The placebo does not contain any active pharmaceutical ingredients and is used to evaluate the effect of colchicine on the incidence of knee or hip replacements in patients with symptomatic knee or hip osteoarthritis.

Efficacy in this clinical trial will be assessed by evaluating the effect of treatment with colchicine 0.5 mg once daily compared to placebo in patients with knee or hip **osteoarthritis** (OA). The primary endpoint for efficacy evaluation is the time from randomization to the first incident of total knee replacement (TKR) or total hip replacement (THR). Secondary endpoints include the course of pain, physical function, and quality of life over the trial period, radiological progression, change in low-grade inflammation at 1 year and end of the study, clinical or radiological onset of OA in new joint groups other than hip and/or knee, use of pain medication, onset of new cardiovascular events, and direct and indirect costs related to treatment and disease burden due to osteoarthritis.

The efficacy parameters will be measured and collected at various timepoints throughout the trial period. The course of pain and physical function will be monitored from randomization over the trial period, while changes in low-grade inflammation will be assessed at 1 year and at the end of the study. The onset of new cardiovascular events, defined as myocardial infarction, peripheral artery disease, ischemia-driven coronary revascularization, ischemic stroke, or cardiovascular death, will also be tracked. The trial is designed as a randomized, double-blind, multicentre study, ensuring rigorous assessment of the efficacy endpoints.