DANNOAC- The Danish Non-vitamin K Antagonist Oral Anticoagulation Study

The primary objective of the DANNOAC study is to conduct a head-to-head comparison of four non-vitamin K antagonist oral anticoagulants (**NOACs**)—Dabigatran Etexilate, Apixaban, Rivaroxaban, and Edoxaban. This evaluation aims to assess their safety and efficacy in preventing death and hospitalizations without increasing the risk of major bleeding in patients diagnosed with **atrial fibrillation** (including atrial flutter), as well as those with **deep vein thrombosis** and/or **pulmonary embolism**. This is clinically relevant as it seeks to determine whether these NOACs are equally effective and safe, which can guide therapeutic decisions in managing these conditions.

Secondary objectives include comparing the risk of major bleedings among the four NOACs. This comparison is crucial for understanding the safety profile of each anticoagulant, thereby informing clinical practice and optimizing patient outcomes.

The clinical trial focuses on evaluating the safety and efficacy of four **NOACs** in patients diagnosed with **atrial fibrillation** (including atrial flutter), deep vein thrombosis, and pulmonary embolism. The study population includes both male and female participants, with age categories ranging from adults to older adults. The trial does not involve a vulnerable population. Participants were selected based on a diagnosis of atrial fibrillation or deep vein thrombosis and/or pulmonary embolism, with a prescription of a NOAC from a Danish pharmacy within 14 days of discharge or outpatient clinic visit. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the safety and efficacy of four **non-vitamin K antagonist oral anticoagulants (NOACs)**: **Dabigatran Etexilate**, **Apixaban**, **Rivaroxaban**, and **Edoxaban**. The study is a randomized, double-blind, controlled trial with an estimated duration from March 2023 to August 2027. The primary objective is to compare these NOACs head-to-head to assess their effectiveness in preventing death and hospitalizations without increasing the risk of major bleeding in patients diagnosed with **atrial fibrillation** (including atrial flutter), **deep vein thrombosis**, or **pulmonary embolism**.

Participants will be involved in the study for a maximum treatment period of 1000 days. The trial includes several key visits: an initial inclusion (screening) visit, multiple follow-up visits, and an end-of-study visit. During the inclusion visit, eligibility criteria will be confirmed, including a diagnosis of atrial fibrillation or venous thromboembolism and a prescription of a NOAC from a Danish pharmacy within 14 days of diagnosis. Follow-up visits will monitor the participants' health status and adherence to the treatment regimen. The end-of-study visit will evaluate the primary and secondary endpoints, which include a composite of stroke, myocardial infarction, thromboembolic events, or all-cause death for atrial fibrillation patients, and new venous thromboembolism or all-cause death for those with venous thromboembolism.

Participant involvement may be terminated early if they experience adverse effects, fail to adhere to the study protocol, or withdraw consent. The trial's design ensures that all four drugs are administered according to their approved indications, maintaining a low-intervention approach. The study aims to provide comprehensive data on the comparative safety and efficacy of these widely used anticoagulants.

The clinical trial involves the administration of **Dabigatran Etexilate**, an experimental medication provided in the form of a hard capsule. The active substance, dabigatran etexilate, is of chemical origin. The medication is administered orally with a maximum daily dose of 300 mg and a maximum total dose of 150 mg. The treatment period is set for a maximum of 1000 days. Participant compliance with the dosing schedule will be monitored throughout the trial.

**Apixaban** is another experimental medication used in this study, provided as a film-coated tablet. The active substance, apixaban, is also of chemical origin. The medication is administered orally with a maximum daily dose of 20 mg and a maximum total dose of 10 mg. The treatment period is similarly set for a maximum of 1000 days. Compliance with the dosing schedule will be closely monitored.

The study also includes the administration of **Rivaroxaban**, which is provided as a film-coated tablet. The active substance, rivaroxaban, is administered orally with a maximum daily dose of 20 mg and a maximum total dose of 20 mg. The treatment period is set for a maximum of 1000 days. Participant adherence to the dosing schedule will be monitored to ensure compliance.

Lastly, **Edoxaban** is used in the trial, provided as a film-coated tablet. The active substance, edoxaban, is of chemical origin and is administered orally. The maximum daily dose is 60 mg, with a maximum total dose of 60 mg. The treatment period is set for a maximum of 1000 days. Monitoring of participant compliance with the dosing schedule is an integral part of the study protocol.

All medications are administered orally, and the trial aims to evaluate the safety and efficacy of these non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation, atrial flutter, deep vein thrombosis, and pulmonary embolism. The study does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Compliance monitoring will be conducted to ensure adherence to the prescribed dosing schedules.

The efficacy of the clinical trial titled "DANNOAC- The Danish Non-vitamin K Antagonist Oral Anticoagulation Study" will be assessed by evaluating the effectiveness of four non-vitamin K antagonist oral anticoagulants (NOACs): **Dabigatran Etexilate**, **Apixaban**, **Rivaroxaban**, and **Edoxaban**. The primary endpoints for efficacy assessment include a composite endpoint for patients with **atrial fibrillation** (and atrial flutter), which consists of stroke, myocardial infarction, thromboembolic events, or all-cause death. For patients with **deep vein thrombosis** and/or **pulmonary embolism**, the primary endpoint is a composite of new venous thromboembolism or all-cause death.

Secondary endpoints will focus on the individual components of the primary endpoints. The trial aims to compare the four NOACs head-to-head to determine their safety and efficacy in preventing death and hospitalizations without increasing the risk of major bleeding. The trial is designed to ensure that all four drugs are used according to their approved indications, as they have been globally approved and utilized for over five years. The study is expected to conclude by August 31, 2027, with recruitment having started on March 1, 2023.