Efficacy and Safety of Low-Dose Colchicine in Preventing Post-Thrombotic Syndrome in Patients with Proximal Lower-Extremity Deep Vein Thrombosis: A Randomized Controlled Trial

The primary objective is to evaluate the safety and efficacy of low-dose colchicine 0.5 mg compared to a placebo in reducing the risk of post-thrombotic syndrome in patients diagnosed with proximal lower-extremity deep vein thrombosis. 5: Efficacy; 4: Safety.

Secondary objectives include:

• Assessment of the risk of post-thrombotic syndrome at 6 months.
• Evaluation of syndrome severity at 6 and 12 months according to clinical categories.
• Measurement of changes in the Villalta score at 6 and 12 months.
• Incidence of venous thromboembolism recurrence and arterial thromboembolism.
• Incidence of a composite of adverse vascular events, major bleeding, and clinically relevant non-major bleeding.
• Assessment of overall mortality during follow-up.
• Evaluation of patient-reported outcomes, including functioning, symptoms, and quality of life, at 6 and 12 months.
• Monitoring of safety parameters, specifically gastrointestinal symptoms, muscle pain, infections, renal failure, neutropenia, and neuropathy.

The sponsor did not provide information regarding the total number of participants. The study population consists of patients aged between 18 and 64 years, including both males and females. Participants are required to have an objectively confirmed, first, acute, and symptomatic proximal lower-extremity deep vein thrombosis involving the popliteal vein or more proximal vessels. The primary objective is to assess the safety and efficacy of low-dose colchicine compared to a placebo in reducing the risk of post-thrombotic syndrome.

This Phase IIb, randomized, controlled trial is designed to evaluate the safety and efficacy of low-dose colchicine 0.5 mg versus placebo in reducing the risk of post-thrombotic syndrome (PTS) in patients diagnosed with acute, symptomatic proximal deep vein thrombosis. Following an initial screening visit to confirm eligibility, participants will be assigned to receive either the active intervention or a placebo once daily via oral use. The study involves follow-up assessments to monitor clinical outcomes, including the Villalta score, incidence of venous thromboembolism, and major bleeding. The total duration of participant involvement is 12 months, with primary endpoints assessed at the end-of-study visit. Secondary outcomes include the evaluation of adverse vascular events, all-cause mortality, and various patient-reported outcome measures. Safety monitoring will track potential gastrointestinal adverse events, muscle pain, infections, renal insufficiency, neutropenia, and neuropathy.

The experimental medication consists of colchicine administered as a 0.5 mg tablet. This substance is intended for oral use and is administered on a once daily dosing schedule.

The control group receives a placebo composed of lactose, extra-fine sugar, spray-dried acacia, and magnesium stearate. This treatment is utilized as a comparator to evaluate the efficacy of the active substance in reducing the risk of post-thrombotic syndrome following deep vein thrombosis.

The primary efficacy endpoint is the incidence of post-thrombotic syndrome, defined as a Villalta score of 5 or greater, at 12 months. Secondary endpoints include the proportion of patients meeting the clinical criteria for post-thrombotic syndrome at 6 months, as well as the distribution of patients across severity categories (mild, moderate, or severe) at both 6 and 12 months. The mean Villalta score and the mean change from baseline will be analyzed at 6 and 12 months to estimate disease severity.

Additional efficacy assessments involve the incidence rates of recurrent venous thromboembolism, arterial thromboembolism, and a composite of adverse vascular events during a follow-up period of up to 12 months. The trial also evaluates the incidence of major bleeding and clinically relevant non-major bleeding based on the International Society of Thrombosis and Haemostasis definition, alongside the all-cause mortality rate. Changes in patient-reported outcome measures from baseline to 6 and 12 months will be assessed using functional scales, including the Patient reported Villalta-scale and Post-venous thromboembolism functional status, as well as health-related quality of life questionnaires such as the EuroQoL-EQ-5D-5L, VEINES QOL/Sym, and PEmb-QoL.