Evaluation of a Single Measurement and Adjustment Strategy for Direct Oral Anticoagulants in Frail Elderly Patients with Atrial Fibrillation or Venous Thromboembolism

The primary objective of this study is to assess the **efficacy** of a Single Measurement and adjustment strategy based on Direct Oral Anticoagulant (DOAC) levels in frail older patients. The focus is on the incidence of complications, specifically thromboembolic events or bleedings, as a composite outcome. This is clinically relevant as it aims to optimize DOAC therapy, potentially reducing adverse events in a vulnerable population with conditions such as atrial fibrillation or venous thromboembolism.

Secondary objectives include evaluating:

• The prevalence of deviant DOAC levels in the frail older population.
• Determinants associated with deviant DOAC levels.
• Differences in quality of life between groups.
• The feasibility and acceptability of the Single Measurement and adjustment strategy through a qualitative study.
• Cost-effectiveness of the intervention.
• Mortality rates.

The clinical trial involves a study population of **frail older patients** diagnosed with **atrial fibrillation** or **venous thromboembolism**. The participants are both male and female, aged over 70 years, and are considered a vulnerable population. The trial specifically targets individuals who are using a **DOAC** (Direct Oral Anticoagulant), with a preference for new users who are initiating treatment. Participants must have a Clinical Frailty Scale (CFS) score greater than 3, be capable of attending outpatient clinic visits if they are community-dwelling, and be able to provide informed consent. The sponsor has not provided information regarding the total number of participants. The selection process for the trial population is based on these criteria, ensuring that the study focuses on a specific demographic that is at risk for thromboembolic events or bleeding complications. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of a **Single Measurement** and adjustment strategy based on direct oral anticoagulant (DOAC) levels in frail older patients with atrial fibrillation or venous thromboembolism. This study is a randomized, double-blind, controlled trial, categorized as a low-intervention clinical trial. The trial aims to assess the impact of this strategy on the incidence of complications, particularly thromboembolic events or bleedings, as a composite outcome. The trial is expected to commence recruitment on September 1, 2025, and conclude by September 1, 2030, with an estimated participant involvement duration of up to 600 days.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 70 years, use of a DOAC, and a Clinical Frailty Scale (CFS) score greater than 3. Following the screening, participants will be randomized to either the intervention or control group. Regular follow-up visits will be scheduled to monitor DOAC levels, assess for any adverse events, and ensure adherence to the study protocol. The end-of-study visit will involve a comprehensive evaluation of the primary and secondary endpoints, including the composite outcome of thromboembolic events or bleedings, prevalence of deviant DOAC levels, and quality of life assessments.

Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include the occurrence of significant adverse events, withdrawal of consent, or any other medical reasons deemed necessary by the study investigators. The trial will utilize oral administration of the study drugs, including **edoxaban tosylate monohydrate**, **apixaban**, **dabigatran etexilate**, and **rivaroxaban**, with a focus on ensuring the safety and efficacy of the intervention in the target population. The study will adhere to all regulatory and ethical guidelines to ensure the integrity and validity of the trial outcomes.

The clinical trial involves the administration of **Edoxaban Tosylate Monohydrate**, a chemical substance classified under the ATC code B01AF03. This medication is provided in a pharmaceutical form identified as PHF00082MIG and is administered orally. The maximum daily and total dose is 60 mg, with a treatment period extending up to 500 days. Edoxaban functions as a **factor Xa inhibitor**, contributing to its anticoagulant properties.

**Apixaban** is another experimental medication used in this study, also a chemical substance and a **factor Xa inhibitor**. It is classified under the ATC code B01AF02 and is provided in the pharmaceutical form PHF00099MIG. Apixaban is administered orally with a maximum daily and total dose of 20 mg, and the treatment period is set for up to 500 days.

The study also includes **Dabigatran Etexilate**, a **thrombin inhibitor** classified under the ATC code B01AE07. This medication is provided in the pharmaceutical form PHF00006MIG and is administered orally. The maximum daily and total dose is 300 mg, with a treatment period of up to 500 days.

**Rivaroxaban**, another **factor Xa inhibitor**, is included in the trial. It is classified under the ATC code B01AF01 and is provided in the pharmaceutical form PHF00082MIG. Rivaroxaban is administered orally with a maximum daily and total dose of 20 mg, and the treatment period extends up to 600 days. The formulation includes **Lactose Monohydrate** as an excipient.

All medications are administered orally, and participant compliance is monitored throughout the study. The trial aims to assess the efficacy of a single measurement and adjustment strategy for direct oral anticoagulants (DOACs) in frail older patients, focusing on the incidence of thromboembolic events or bleeding as a composite outcome. No non-experimental treatments, such as standard-of-care therapy or placebo, are specified in the trial data provided.

The efficacy of the clinical trial will be assessed by evaluating the impact of a Single Measurement and adjustment strategy based on Direct Oral Anticoagulant (DOAC) levels in frail older patients. The primary endpoint for efficacy is a composite outcome of thromboembolic events or bleedings. Bleeding is defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria, encompassing major bleeding or clinically relevant non-major (CRNM) bleeding. Thromboembolic events include ischemic stroke, transient ischemic attack (TIA), and peripheral thromboembolism.

Secondary endpoints include the prevalence of deviant DOAC levels in the frail older population, determinants associated with deviant DOAC levels, differences in quality of life between groups, feasibility and acceptability of the Single Measurement and adjustment strategy through a qualitative study, cost-effectiveness of the intervention, and mortality rates. These parameters will be measured and analyzed to provide comprehensive insights into the efficacy of the intervention strategy.