The Danish Non-vitamin K Antagonist Oral Anticoagulation Study in Patients With Venous Thromboembolism (DANNOAC-VTE)

NCT ID: NCT03129555

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 5000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2029-03-31

Brief Summary

No randomized head-to-head comparison between the individual Non-vitamin K Antagonist Oral Anticoagulants (NOAC) exists. The DANNOAC-VTE study is a nationwide cluster randomized cross-over study comparing efficacy and safety of the four NOACs, edoxaban, apixaban, rivaroxaban and dabigatran for oral anticoagulation in venous thromboembolism across Danish hospitals.

Detailed Description

No randomized head-to-head comparison between the individual Non-vitamin K Antagonist Oral Anticoagulants (NOAC) exists, but such data are warranted to evaluate if the four NOACs are equal in treatment of venous thromboembolism (VTE) without an additional cost of increased bleeding risk. Furthermore, classic randomized trials are highly selective, as elderly and/or fragile patients and patients with comorbidity are underrepresented. Therefore, there is a need of randomized trials that include a broader population of patients.

The DANNOAC-VTE study is a nationwide cluster randomized cross-over study comparing efficacy and safety of the four NOACs, edoxaban, apixaban, rivaroxaban and dabigatran for oral anticoagulation in VTE across Danish hospitals. The aim of the present study is to: 1) examine if the four NOACs are equally effective in treatment of VTE without increasing the risk of major bleeding requiring hospitalization; 2) conduct a randomized study that includes elderly and fragile patients and patients with comorbidity that would otherwise not be included in a traditional randomized clinical trial.

For a variety of reasons, Danish hospitals and clinicians often prefer one particular NOAC. This can make work simpler for the busy clinician, although there may also be economic advantages on a local or a regional larger scale. For a period of two years, this study will replace this individually or hospital preferred selection with a random selection. The hospitals and clinics that participate in this study will be randomly selected to primarily use one specific NOAC for 6 months at a time during a total period of two years. This only applies to patients with VTE that are selected by the physician to be eligible for NOAC treatment. VTE refers to deep vein thrombosis and pulmonary embolism, or a combination of both.

Endpoints

• Primary efficacy outcome: a composite endpoint of new venous thromboembolism or all-cause death.
• Secondary efficacy outcomes: Individually components of the primary endpoints; new venous thromboembolism or all-cause death.
• Primary safety outcome: bleeding requiring hospitalization.
• Other effect measures:

1. discontinuation of therapy.

2. adherence to therapy.

3. other reasons of admission to hospital than included in the primary and secondary endpoint.

• Sensitivity analyses:

1. primary endpoint stratified by gender.

2. primary endpoint stratified by age (≤65, 65-75, >75 years of age).

3. primary endpoint stratified by levels of the CHA2DS2VASc score (0-1, 2-3, >3).

4. primary endpoint with exclusion of clusters with non-compliance greater than 20% of cluster randomization.

5. primary endpoint where the actual treatment is used instead of the allocated treatment.

6. primary safety endpoint stratified by HAS-BLED score.

Information of endpoints and comorbidity is obtained from the Danish National Patient Register based on ICD-10 diagnostic codes and information of vital status and date of death will be obtained from the Central Person Register. Drug discontinuation and adherence will be examined using information from the Danish Registry of Medicinal Product Statistics. The prespecified endpoints will be evaluated after 6 months as intention-to-treat analysis. In addition, the prespecified endpoints will be evaluated after 12 months and 5 years.

A cluster is defined as a hospital or a cardiology clinic. The Clusters will be enrolled in the study from 1. of April 2023 to 1. October 2023.

Conditions

Deep Vein Thrombosis; Pulmonary Embolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Dabigatran

After randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.

Group Type: ACTIVE_COMPARATOR

Dabigatran Etexilate Oral Capsule

Intervention Type: DRUG

After cluster randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Rivaroxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Edoxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Apixaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Rivaroxaban

After randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.

Group Type: ACTIVE_COMPARATOR

Dabigatran Etexilate Oral Capsule

Intervention Type: DRUG

After cluster randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Rivaroxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Edoxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Apixaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Edoxaban

After randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.

Group Type: ACTIVE_COMPARATOR

Dabigatran Etexilate Oral Capsule

Intervention Type: DRUG

After cluster randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Rivaroxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Edoxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Apixaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Apixaban

After randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.

Group Type: ACTIVE_COMPARATOR

Dabigatran Etexilate Oral Capsule

Intervention Type: DRUG

After cluster randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Rivaroxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Edoxaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Apixaban Oral Tablet

Intervention Type: DRUG

After cluster randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Interventions

Dabigatran Etexilate Oral Capsule

After cluster randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Intervention Type: DRUG

Rivaroxaban Oral Tablet

After cluster randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Intervention Type: DRUG

Edoxaban Oral Tablet

After cluster randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Intervention Type: DRUG

Apixaban Oral Tablet

After cluster randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time. It is the clusters and not the patient that are randomized.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• A diagnosis of VTE in outpatient clinic or as discharge diagnosis after hospitalization.
• A claimed prescription of a NOAC from a Danish pharmacy within 14 days of discharge or outpatient clinic visit.

Exclusion Criteria

• A prescription of a NOAC within 90 days prior to hospitalization or outpatient clinic visit for VTE.
• Patients with NOAC preference apart from preference consistent with current cluster randomized NOAC.
• Other contraindications mentioned in the "Summary of Product Characteristics" for the respective NOAC.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Herlev and Gentofte Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gunnar Gislason

MD,PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gunnar H Gislason, MD, PhD

Role: STUDY_CHAIR

Herlev Gentofte Hospital

Locations

Aarhus University Hospital

Aarhus, , Denmark

Bispebjerg and Frederiksberg Hospital

Copenhagen, , Denmark

Bispebjerg Hospital

Copenhagen NV, , Denmark

Amager Hospital

Copenhagen S, , Denmark

Rigshospitalet

Copenhagen Ø, , Denmark

Esbjerg Hospital

Esbjerg, , Denmark

Nordsjællands Hospital - Frederiksund

Frederikssund, , Denmark

Herlev Gentofte Hospital

Gentofte Municipality, , Denmark

Glostrup Hospital - Department of Emergency Medicine

Glostrup Municipality, , Denmark

Glostrup Hospital - Department of Medicine / Cardiology

Glostrup Municipality, , Denmark

Glostrup Hospital - Department of Neurology

Glostrup Municipality, , Denmark

Herlev-Gentofte Hospital - Department of Medicine

Herlev, , Denmark

Nordsjællands Hospital - Hillerød

Hillerød, , Denmark

Hjørring Hospital

Hjørring, , Denmark

Holbæk Hospital

Holbæk, , Denmark

Hvidovre Hospital

Hvidovre, , Denmark

Næstved Hospital

Næstved, , Denmark

Odense University Hospital - Department of Cardiology

Odense, , Denmark

Odense University Hospital - Department of Emergency Medicine

Odense, , Denmark

Odense University Hospital - Department of Geriatrics

Odense, , Denmark

Zealand University Hospital - Department of Neurology

Roskilde, , Denmark

Zealand University Hospital Roskilde - Department of Cardiology

Roskilde, , Denmark

Bornhoms Hospital

Rønne, , Denmark

Slagelse Hospital

Slagelse, , Denmark

Odense University Hospital Svendborg

Svendborg, , Denmark

Vejle Hospital

Vejle, , Denmark

Countries

Denmark

Related Links

http://dannoac.dk

DANNOAC study webpage

Other Identifiers

DHF2

Identifier Type: -

Identifier Source: org_study_id