- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03129555
The Danish Non-vitamin K Antagonist Oral Anticoagulation Study in Patients With Venous Thromboembolism (DANNOAC-VTE) (DANNOAC-VTE)
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.
Study Overview
Status
Conditions
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:
- discontinuation of therapy.
- adherence to therapy.
- other reasons of admission to hospital than included in the primary and secondary endpoint.
Sensitivity analyses:
- primary endpoint stratified by gender.
- primary endpoint stratified by age (≤65, 65-75, >75 years of age).
- primary endpoint stratified by levels of the CHA2DS2VASc score (0-1, 2-3, >3).
- primary endpoint with exclusion of clusters with non-compliance greater than 20% of cluster randomization.
- primary endpoint where the actual treatment is used instead of the allocated treatment.
- 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
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Casper N Bang, MD, PhD
- Email: casper.niels.furbo.bang@regionh.dk
Study Contact Backup
- Name: Gunnar H Gislason, MD, PhD
- Phone Number: 29341524
- Email: Gunnar.Gislason@regionh.dk
Study Locations
-
-
-
Aarhus, Denmark, 8200
- Not yet recruiting
- Aarhus University Hospital
-
Contact:
- Erik Grove, MD
- Email: erikgrove@dadlnet.dk
-
Principal Investigator:
- Erik L Grove, MD
-
Copenhagen, Denmark, 2400
- Recruiting
- Bispebjerg and Frederiksberg Hospital
-
Contact:
- Thomas Hermann, MD, PhD
- Email: thomas.steffen.hermann@regionh.dk
-
Copenhagen NV, Denmark, 2400
- Recruiting
- Bispebjerg Hospital
-
Contact:
- Birgitte U Nygaard, MD
- Phone Number: 38 63 50 00
-
Copenhagen S, Denmark, 2300
- Recruiting
- Amager Hospital
-
Contact:
- Jens Brønnum-Schou, MD
- Phone Number: +45 32 34 32 34
- Email: jens.Broennum-Schou@regionh.dk
-
Copenhagen Ø, Denmark, 2100
- Not yet recruiting
- Rigshospitalet
-
Contact:
- Lars Køber, MD
- Phone Number: +45 35 45 35 45
- Email: Lars.Koeber@regionh.dk
-
Esbjerg, Denmark, 6700
- Recruiting
- Esbjerg Hospital
-
Contact:
- Majed Husain, MD
- Email: Majed.H.husain@rsyd.dk
-
Principal Investigator:
- Majed Husain, MD
-
Frederikssund, Denmark, 3600
- Recruiting
- Nordsjællands Hospital - Frederiksund
-
Contact:
- Louise Schierbeck, MD
- Phone Number: +45 48 29 50 00
- Email: louise.schierbeck.01@regionh.dk
-
Gentofte, Denmark, 2900
- Recruiting
- Herlev Gentofte Hospital
-
Contact:
- Gunnar Gislason, MD
- Phone Number: +45 38 67 38 67
- Email: Gunnar.Gislason@regionh.dk
-
Principal Investigator:
- Jonas Olesen, MD
-
Glostrup, Denmark, 2600
- Recruiting
- Glostrup Hospital - Department of Emergency Medicine
-
Contact:
- Ekim Seven, MD
- Email: ekim.seven@regionh.dk
-
Glostrup, Denmark, 2600
- Recruiting
- Glostrup Hospital - Department of Medicine / Cardiology
-
Contact:
- Jesper P Hansen, MD
- Email: jesper.park.hansen.01@regionh.dk
-
Glostrup, Denmark, 2600
- Recruiting
- Glostrup Hospital - Department of Neurology
-
Contact:
- Helle Iversen, MD
- Phone Number: +45 38 63 38 63
- Email: helle.klingenberg.iversen@regionh.dk
-
Herlev, Denmark, 2730
- Recruiting
- Herlev-Gentofte Hospital - Department of Medicine
-
Contact:
- Kasper Iversen, MD
- Email: kasper.karmark.iversen@regionh.dk
-
Hillerød, Denmark, 3400
- Recruiting
- Nordsjællands Hospital - Hillerød
-
Contact:
- Louise Schierbeck, MD
- Phone Number: +45 48 29 48 29
- Email: louise.schierbeck.01@regionh.dk
-
Hjørring, Denmark, 9800
- Not yet recruiting
- Hjørring Hospital
-
Contact:
- Albert M Johnsen, MD
- Email: albert.marni.joensen@rn.dk
-
Principal Investigator:
- Albert M Johnsen, MD
-
Holbæk, Denmark, 4300
- Recruiting
- Holbæk Hospital
-
Contact:
- Anne MB Soja, MD
- Email: amsj@regionsjaelland.dk
-
Sub-Investigator:
- Peter Hallas, MD
-
Principal Investigator:
- Anne MB Soja, MD
-
Hvidovre, Denmark, 2650
- Recruiting
- Hvidovre Hospital
-
Contact:
- Jens Hove, MD
- Phone Number: 38 62 38 62
- Email: Jens.Dahlgaard.Hove@regionh.dk
-
Sub-Investigator:
- Christian Rasmussen, MD
-
Næstved, Denmark, 4700
- Not yet recruiting
- Næstved Hospital
-
Contact:
- Frida Yrjans, MD
- Email: fyr@regionsjaelland.dk
-
Odense, Denmark, 5000
- Recruiting
- Odense University Hospital - Department of Cardiology
-
Contact:
- Gro Egholm, MD
- Email: gro.egholm@rsyd.dk
-
Principal Investigator:
- Gro Egholm, MD
-
Odense, Denmark, 5000
- Recruiting
- Odense University Hospital - Department of Emergency Medicine
-
Contact:
- Mikkel Brabrand, MD
- Email: Mikkel.Brabrand@rsyd.dk
-
Principal Investigator:
- Mikkel Brabrand, MD
-
Odense, Denmark, 5000
- Recruiting
- Odense University Hospital - Department of Geriatrics
-
Contact:
- Azra Osmanagic, MD
- Email: Azra.Osmanagic@rsyd.dk
-
Principal Investigator:
- Azra Osmanagic, MD
-
Sub-Investigator:
- Jesper Ryg, MD
-
Roskilde, Denmark, 4000
- Recruiting
- Zealand University Hospital - Department of Neurology
-
Contact:
- Troels Wienecke, MD
- Email: trw@regionsjaelland.dk
-
Roskilde, Denmark, 4000
- Not yet recruiting
- Zealand University Hospital Roskilde - Department of Cardiology
-
Contact:
- Christian Bang, MD
- Email: cbng@regionsjaelland.dk
-
Rønne, Denmark, 3700
- Recruiting
- Bornhoms Hospital
-
Contact:
- Kjeld Kristensen, MD
- Phone Number: +45 38 67 00 00
- Email: kjeld.skoedebjerg.kristensen@regionh.dk
-
Slagelse, Denmark, 4200
- Not yet recruiting
- Slagelse Hospital
-
Contact:
- Gitte G Fornitz, MD
- Email: gfor@regionsjaelland.dk
-
Svendborg, Denmark, 5700
- Recruiting
- Odense University Hospital Svendborg
-
Contact:
- Jess Lambrechtsen, MD
- Email: Jess.Lambrechtsen@rsyd.dk
-
Vejle, Denmark, 7100
- Recruiting
- Vejle Hospital
-
Contact:
- Lone K Andersen, MD
- Email: Lone.Kaerslund.Andersen@rsyd.dk
-
Principal Investigator:
- Lone K Andersen, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
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
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.
|
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.
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.
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.
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.
|
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.
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.
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.
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.
|
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.
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.
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.
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.
|
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.
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.
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.
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
Sponsor
Collaborators
Investigators
- Study Chair: Gunnar H Gislason, MD, PhD, Herlev Gentofte Hospital
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Embolism and Thrombosis
- Embolism
- Thrombosis
- Venous Thrombosis
- Thromboembolism
- Venous Thromboembolism
- Pulmonary Embolism
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Factor Xa Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Rivaroxaban
- Dabigatran
- Apixaban
- Edoxaban
Other Study ID Numbers
- DHF2
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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