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

July 5, 2023 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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

5000

Phase

  • 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 Backup

Study Locations

  • Denmark
      • Aarhus, Denmark, 8200
        • Not yet recruiting
        • Aarhus University Hospital
        • Contact:
        • Principal Investigator:
          • Erik L Grove, MD
      • Copenhagen, Denmark, 2400
      • Copenhagen NV, Denmark, 2400
        • Recruiting
        • Bispebjerg Hospital
        • Contact:
          • Birgitte U Nygaard, MD
          • Phone Number: 38 63 50 00
      • Copenhagen S, Denmark, 2300
      • Copenhagen Ø, Denmark, 2100
        • Not yet recruiting
        • Rigshospitalet
        • Contact:
      • Esbjerg, Denmark, 6700
        • Recruiting
        • Esbjerg Hospital
        • Contact:
        • Principal Investigator:
          • Majed Husain, MD
      • Frederikssund, Denmark, 3600
      • Gentofte, Denmark, 2900
        • Recruiting
        • Herlev Gentofte Hospital
        • Contact:
        • Principal Investigator:
          • Jonas Olesen, MD
      • Glostrup, Denmark, 2600
        • Recruiting
        • Glostrup Hospital - Department of Emergency Medicine
        • Contact:
      • Glostrup, Denmark, 2600
      • Glostrup, Denmark, 2600
      • Herlev, Denmark, 2730
      • Hillerød, Denmark, 3400
      • Hjørring, Denmark, 9800
        • Not yet recruiting
        • Hjørring Hospital
        • Contact:
        • Principal Investigator:
          • Albert M Johnsen, MD
      • Holbæk, Denmark, 4300
        • Recruiting
        • Holbæk Hospital
        • Contact:
        • Sub-Investigator:
          • Peter Hallas, MD
        • Principal Investigator:
          • Anne MB Soja, MD
      • Hvidovre, Denmark, 2650
        • Recruiting
        • Hvidovre Hospital
        • Contact:
        • Sub-Investigator:
          • Christian Rasmussen, MD
      • Næstved, Denmark, 4700
      • Odense, Denmark, 5000
        • Recruiting
        • Odense University Hospital - Department of Cardiology
        • Contact:
        • Principal Investigator:
          • Gro Egholm, MD
      • Odense, Denmark, 5000
        • Recruiting
        • Odense University Hospital - Department of Emergency Medicine
        • Contact:
        • Principal Investigator:
          • Mikkel Brabrand, MD
      • Odense, Denmark, 5000
        • Recruiting
        • Odense University Hospital - Department of Geriatrics
        • Contact:
        • Principal Investigator:
          • Azra Osmanagic, MD
        • Sub-Investigator:
          • Jesper Ryg, MD
      • Roskilde, Denmark, 4000
        • Recruiting
        • Zealand University Hospital - Department of Neurology
        • Contact:
      • Roskilde, Denmark, 4000
        • Not yet recruiting
        • Zealand University Hospital Roskilde - Department of Cardiology
        • Contact:
      • Rønne, Denmark, 3700
      • Slagelse, Denmark, 4200
      • Svendborg, Denmark, 5700
      • Vejle, Denmark, 7100

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

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
Intervention / Treatment
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

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

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

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

Herlev and Gentofte Hospital

Collaborators

Danish Society of Cardiology

Investigators

  • 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)

April 1, 2023

Primary Completion (Estimated)

March 31, 2027

Study Completion (Estimated)

March 31, 2029

Study Registration Dates

First Submitted

April 18, 2017

First Submitted That Met QC Criteria

April 21, 2017

First Posted (Actual)

April 26, 2017

Study Record Updates

Last Update Posted (Actual)

July 6, 2023

Last Update Submitted That Met QC Criteria

July 5, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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