Efficacy of Apixaban in Pain Management for Patients with Venous Malformations and Localized Intravascular Coagulation: A Blinded Crossover Study

The primary objective of this study is to evaluate the **efficacy** of apixaban on pain intensity in patients with venous malformations. This is clinically relevant as venous malformations can cause significant pain, impacting the quality of life and daily functioning of affected individuals. By assessing the impact of apixaban, a known anticoagulant, on pain levels, the study aims to provide insights into potential therapeutic benefits for managing pain associated with this condition.

Secondary objectives include:

• Investigating the efficacy of apixaban on coagulation parameters.
• Assessing the impact of apixaban on quality of life.
• Determining the minimum effective dose of apixaban for pain reduction in venous malformations.
• Evaluating the safety profile of apixaban in this patient population.
• Exploring the long-term effects of apixaban over a three-month period.
• Examining the efficacy of apixaban on the amount of thrombi in venous malformations.

The clinical trial focuses on evaluating the efficacy of apixaban in reducing pain intensity associated with **venous malformation**. The study population includes both male and female participants, aged between 18 and 85 years. Participants are required to have a simple venous malformation confirmed by MRI, with localized intravascular coagulation indicated by a d-dimer level greater than twice the upper reference area. Additionally, participants must experience localized pain in the venous malformation, with a Numeric Rating Scale (NRS) score of 4 or higher, which significantly inhibits daily activities or interferes with sleep. The trial does not include vulnerable populations. 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 as a **randomized**, **double-blind**, **controlled** study to evaluate the efficacy of **apixaban** in patients with **venous malformations** associated with localized intravascular coagulation. The trial will be conducted over a period of approximately three years, with an estimated recruitment start date of October 1, 2024, and an estimated end date of December 31, 2027. Participants will be randomly assigned to receive either apixaban or a placebo, with the primary endpoint being the difference in self-reported pain intensity before and eight weeks after starting treatment. Secondary endpoints include changes in coagulation parameters, quality of life, and the amount of thrombi in venous malformations, as well as the number and severity of bleeding episodes.

The study will involve several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-85 years), confirmed simple venous malformation via MRI, and localized pain with a numerical rating scale (NRS) score of 4 or higher. Follow-up visits will occur at regular intervals to monitor treatment effects and safety, with assessments of pain intensity, coagulation parameters, and quality of life. The end-of-study visit will conclude the trial, with a final evaluation of the primary and secondary endpoints.

Participant involvement is expected to last for the duration of the treatment period, which is a maximum of 32 weeks. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial is categorized as a Phase IV study, indicating it is conducted after the drug has been approved for use, to gather additional information on its efficacy and safety in a broader patient population.

The clinical trial involves the administration of **apixaban**, an oral anticoagulant, as the experimental medication. The pharmaceutical form of the medication is a **film-coated tablet**, specifically branded as "Teva GmbH filmovertrukne tabletter 5 mg." Each tablet contains 5 mg of the active substance, apixaban, which is of chemical origin. The medication is administered orally, with a maximum daily dose of 10 mg. The total maximum dose over the course of the study is 2240 mg, with a treatment period not exceeding 32 days. The trial aims to evaluate the efficacy of apixaban in reducing pain intensity in patients with painful venous malformations associated with localized intravascular coagulation.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for use in this study. The trial is designed as a single-center, blinded crossover study, ensuring that the administration of the experimental medication is conducted under controlled conditions to maintain the integrity of the trial results. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

The efficacy of **apixaban** in patients with painful venous malformations with localized intravascular coagulation will be assessed through a single-center blinded crossover study. The primary endpoint for evaluating efficacy is the difference in self-reported pain intensity between apixaban and placebo, measured before and 8 weeks after the initiation of treatment. Secondary endpoints include changes in coagulation parameters, quality of life, and the amount of thrombi in venous malformations, all assessed before and 8 weeks after starting treatment. Additionally, changes in pain intensity and quality of life will be evaluated three months after dose reduction, and the number and severity of bleeding episodes will be registered under treatment with both apixaban and placebo. The study will also assess changes in pain intensity three months after continuing apixaban at a dose of 5 mg twice daily. These efficacy parameters will be collected and analyzed at specified timepoints to determine the therapeutic impact of apixaban in the target patient population.