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

May 14, 2025 updated by: Gunnar Gislason, Herlev and Gentofte Hospital

The Danish Non-vitamin K Antagonist Oral Anticoagulation Study. A Cluster Randomized Study Comparing Safety and Efficacy of Edoxaban, Apixaban, Rivaroxaban and Dabigatran for Oral Anticoagulation in Patients With Venous Thromboembolism.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5000

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
      • Aarhus, Denmark, 8200
        • Aarhus University Hospital
      • Copenhagen, Denmark, 2400
        • Bispebjerg and Frederiksberg Hospital
      • Copenhagen NV, Denmark, 2400
        • Bispebjerg Hospital
      • Copenhagen S, Denmark, 2300
        • Amager Hospital
      • Copenhagen Ø, Denmark, 2100
        • Rigshospitalet
      • Esbjerg, Denmark, 6700
        • Esbjerg Hospital
      • Frederikssund, Denmark, 3600
        • Nordsjællands Hospital - Frederiksund
      • Gentofte, Denmark, 2900
        • Herlev Gentofte Hospital
      • Glostrup, Denmark, 2600
        • Glostrup Hospital - Department of Emergency Medicine
      • Glostrup, Denmark, 2600
        • Glostrup Hospital - Department of Medicine / Cardiology
      • Glostrup, Denmark, 2600
        • Glostrup Hospital - Department of Neurology
      • Herlev, Denmark, 2730
        • Herlev-Gentofte Hospital - Department of Medicine
      • Hillerød, Denmark, 3400
        • Nordsjællands Hospital - Hillerød
      • Hjørring, Denmark, 9800
        • Hjørring Hospital
      • Holbæk, Denmark, 4300
        • Holbæk Hospital
      • Hvidovre, Denmark, 2650
        • Hvidovre Hospital
      • Næstved, Denmark, 4700
        • Næstved Hospital
      • Odense, Denmark, 5000
        • Odense University Hospital - Department of Cardiology
      • Odense, Denmark, 5000
        • Odense University Hospital - Department of Emergency Medicine
      • Odense, Denmark, 5000
        • Odense University Hospital - Department of Geriatrics
      • Roskilde, Denmark, 4000
        • Zealand University Hospital - Department of Neurology
      • Roskilde, Denmark, 4000
        • Zealand University Hospital Roskilde - Department of Cardiology
      • Rønne, Denmark, 3700
        • Bornhoms Hospital
      • Slagelse, Denmark, 4200
        • Slagelse Hospital
      • Svendborg, Denmark, 5700
        • Odense University Hospital Svendborg
      • Vejle, Denmark, 7100
        • Vejle Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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.
Drug: 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.
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.
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.
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.
Active Comparator: 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.
Drug: 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.
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.
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.
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.
Active Comparator: 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.
Drug: 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.
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.
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.
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.
Active Comparator: 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.
Drug: 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.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Primary efficacy outcome: a composite endpoint of new venous thromboembolism or all-cause death.
Time Frame: 6 months.
First occurrence of new venous thromboembolism or all-cause death. 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. Information of prescribed drug will be obtained using information from the Danish Registry of Medicinal Product Statistics.
6 months.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Secondary efficacy outcome: New venous thromboembolism.
Time Frame: 6 months.
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. Information of prescribed drug will be obtained using information from the Danish Registry of Medicinal Product Statistics.
6 months.
Secondary efficacy outcome: All-cause death.
Time Frame: 6 months.
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. Information of prescribed drug will be obtained using information from the Danish Registry of Medicinal Product Statistics.
6 months.
Primary safety outcome: bleeding requiring hospitalization.
Time Frame: 6 months.
First occurrence of bleeding requiring hospitalization. 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. Information of prescribed drug will be obtained using information from the Danish Registry of Medicinal Product Statistics.
6 months.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Discontinuation of therapy.
Time Frame: 6 months.
Drug discontinuation will be examined using information from the Danish Registry of Medicinal Product Statistics.
6 months.
Adherence to therapy.
Time Frame: 6 months.
Drug adherence will be examined using information from the Danish Registry of Medicinal Product Statistics.
6 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Herlev and Gentofte Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Danish Society of Cardiology

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Gunnar H Gislason, MD, PhD, Herlev Gentofte Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 15, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DHF2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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