Venous ThromboembolismPhase 3DARINANCT01431456
Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery
A Phase 3 study testing Dabigatran, Rivaroxaban and Nadroparin in people with Venous Thromboembolism, run by Martini Hospital Groningen at 1 site in Netherlands.
Trial summary
Rationale: After total knee arthroplasty (TKA) surgery, patients are at risk to develop venous thromboembolism (VTE) or deep venous thrombosis (DVT) potentially resulting in a fatal pulmonary embolism (PE). Read more about this study
- Who is it for?
- Ages 18 to 110 years
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Dabigatran, Rivaroxaban and Nadroparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2013to Oct 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients > 18 years and weighing more than 40 kg who are scheduled for primary elective total knee arthroplasty according to the 'joint care program' and want to provided signed informed consent are eligible for the study.
Who cannot join
- a known inherited or acquired clinically significant active high risk of bleeding or bleeding disorder;
- major surgery, trauma, uncontrolled severe arterial hypertension, or myocardial infarction within the last 3 months;
- history of acute intracranial disease or hemorrhagic stroke;
- gastrointestinal or urogenital bleeding or ulcer disease within the last 6 months;
- cirrhotic patients with moderate hepatic impairment (aspartate or alanine aminotransferase (AST, ALT) levels higher than 2x the upper limit of the normal range (ULN) within the last month);
- severe renal insufficiency (creatinine clearance < 30 mL/min);
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- treatment with anticoagulants during study drug treatment;
- active malignant disease;
- pregnancy or breastfeeding;
- and unable to give informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Pilot Study Comparing the Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery
Rationale:
After total knee arthroplasty (TKA) surgery, patients are at risk to develop venous thromboembolism (VTE) or deep venous thrombosis (DVT) potentially resulting in a fatal pulmonary embolism (PE). Two novel agents, dabigatran and rivaroxaban, recently gained market authorisation for prevention of venous thromboembolism after knee arthroplasty.
Read more
However, there are no clinical trials with dabigatran and/or rivaroxaban and the comparator nadroparin.
Nadroparin is used in the most Dutch departments of orthopaedic surgery after total knee arthroplasty. Also safety of the new oral agents with long term use of 42 days is not available for total knee arthroplasty.
Our aim is to compare the long term use of dabigatran and rivaroxaban versus nadroparin on safety after total knee arthroplasty (TKA) in a clinical explorative pilot study by observing the incidence of major bleeding and clinical relevant non-major bleeding using a standardized model of bleeding definitions.
Objective:
The primary objective of this study is to compare the clinical safety with long term use of the oral once daily unmonitored thrombin inhibitors dabigatran and rivaroxaban versus subcutaneous administered nadroparin by observing the incidence of major bleeding and clinical relevant non-major bleeding in patients after knee arthroplasty surgery.
The secondary objectives of this study are effectivity of the agents, compliance, hospital stay, re-hospitalisation, outpatient clinic visits and interventions following complications. Additionally, coagulation monitoring, knee flexion range of motion, Knee injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS) and relationship between health statuses and surgery parameters will be evaluated.
Study design:
The study is designed as non-inferiority randomized open label controlled pilot study. A total of 150 patients will be included, 50 patients in each treatment group (dabigatran, rivaroxaban and nadroparin).
Study population:
Patients ≥ 18 years and weighing more than 40 kg, participate in the 'joint care program' for primary elective total knee arthroplasty and want to provide signed informed consent are eligible for the study.
Intervention:
Patients receive subcutaneously nadroparin or oral rivaroxaban or oral dabigatran after knee replacement surgery.
Main study parameters/endpoints:
The primary safety outcome is the incidence of bleeding events occurring during the study period of 135 days (including follow-up). Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines.
- Conditions
- Venous Thromboembolism
- Being tested
- Dabigatran, Rivaroxaban, Nadroparin
- Keywords
- Prevention, venous thromboembolism after knee arthroplasty
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DabigatranDrug
Dabigatran
RivaroxabanDrug
Rivaroxaban
NadroparinDrug
Nadroparin
| Study group | Role | What they receive |
|---|---|---|
| Dabigatran | Active comparator | Dabigatran Receives: Drug: Dabigatran |
| Rivaroxaban | Active comparator | Rivaroxaban Receives: Drug: Rivaroxaban |
| Nadroparin | Active comparator | Nadroparin Receives: Drug: Nadroparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary safety outcome is the incidence of bleeding events occurring during the study period of 135 days (including follow-up). Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines
Major and clinically relevant non-major bleeding
Measured: 135 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2011 (estimated)
- Study startSep 2013
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Martini Hospital Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marinus van Hulst, Martini Hospital Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01431456
- Sponsor's protocol ID
- DARINA
- Acronym
- DARINA
- Status last verified
- Jun 2018
- First submitted
- 7 Sep 2011
- Last updated
- 7 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
van der Veen L, Segers M, van Raay JJ, Gerritsma-Bleeker CL, Brouwer RW, Veeger NJ, van Hulst M. Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study. BMJ Open. 2021 Jan 18;11(1):e040336. doi: 10.1136/bmjopen-2020-040336.
PubMed 33462096Veen Lv, van Raay JJ, Gerritsma-Bleeker CL, Veeger NJ, Hulst Mv. Direct treatment comparison of DAbigatran and RIvaroxaban versus NAdroparin in the prevention of venous thromboembolism after total knee arthroplasty surgery: design of a randomised pilot study (DARINA). BMJ Open. 2013 Jan 24;3(1):e002218. doi: 10.1136/bmjopen-2012-002218.
PubMed 23355673
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Pilot Study Comparing the Safety of DAbigatran and RIvaroxaban Versus NAdroparin in the Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery
- ClinicalTrials.gov ID
- NCT01431456
- Acronym / sponsor ID
- DARINA / DARINA
- Conditions
- Venous Thromboembolism
- Keywords
- Prevention, venous thromboembolism after knee arthroplasty
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Martini Hospital GroningenUniversity, hospital or other
- Study start
- Sep 2013 (actual)
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 9 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale:
After total knee arthroplasty (TKA) surgery, patients are at risk to develop venous thromboembolism (VTE) or deep venous thrombosis (DVT) potentially resulting in a fatal pulmonary embolism (PE). Two novel agents, dabigatran and rivaroxaban, recently gained market authorisation for prevention of venous thromboembolism after knee arthroplasty.
However, there are no clinical trials with dabigatran and/or rivaroxaban and the comparator nadroparin.
Nadroparin is used in the most Dutch departments of orthopaedic surgery after total knee arthroplasty. Also safety of the new oral agents with long term use of 42 days is not available for total knee arthroplasty.
Our aim is to compare the long term use of dabigatran and rivaroxaban versus nadroparin on safety after total knee arthroplasty (TKA) in a clinical explorative pilot study by observing the incidence of major bleeding and clinical relevant non-major bleeding using a standardized model of bleeding definitions.
Objective:
The primary objective of this study is to compare the clinical safety with long term use of the oral once daily unmonitored thrombin inhibitors dabigatran and rivaroxaban versus subcutaneous administered nadroparin by observing the incidence of major bleeding and clinical relevant non-major bleeding in patients after knee arthroplasty surgery.
The secondary objectives of this study are effectivity of the agents, compliance, hospital stay, re-hospitalisation, outpatient clinic visits and interventions following complications. Additionally, coagulation monitoring, knee flexion range of motion, Knee injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS) and relationship between health statuses and surgery parameters will be evaluated.
Study design:
The study is designed as non-inferiority randomized open label controlled pilot study. A total of 150 patients will be included, 50 patients in each treatment group (dabigatran, rivaroxaban and nadroparin).
Study population:
Patients ≥ 18 years and weighing more than 40 kg, participate in the 'joint care program' for primary elective total knee arthroplasty and want to provide signed informed consent are eligible for the study.
Intervention:
Patients receive subcutaneously nadroparin or oral rivaroxaban or oral dabigatran after knee replacement surgery.
Main study parameters/endpoints:
The primary safety outcome is the incidence of bleeding events occurring during the study period of 135 days (including follow-up). Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dabigatran | Active comparator | Drug: DabigatranDabigatran |
| Rivaroxaban | Active comparator | Drug: RivaroxabanRivaroxaban |
| Nadroparin | Active comparator | Drug: NadroparinNadroparin |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients > 18 years and weighing more than 40 kg who are scheduled for primary elective total knee arthroplasty according to the 'joint care program' and want to provided signed informed consent are eligible for the study.
Key exclusion criteria (10 listed)
- a known inherited or acquired clinically significant active high risk of bleeding or bleeding disorder;
- major surgery, trauma, uncontrolled severe arterial hypertension, or myocardial infarction within the last 3 months;
- history of acute intracranial disease or hemorrhagic stroke;
- gastrointestinal or urogenital bleeding or ulcer disease within the last 6 months;
- cirrhotic patients with moderate hepatic impairment (aspartate or alanine aminotransferase (AST, ALT) levels higher than 2x the upper limit of the normal range (ULN) within the last month);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DabigatranDabigatran | Drug | Dabigatran |
| RivaroxabanRivaroxaban | Drug | Rivaroxaban |
| NadroparinNadroparin | Drug | Nadroparin |
Primary outcome
The primary safety outcome is the incidence of bleeding events occurring during the study period of 135 days (including follow-up). Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines
Time frame: 135 days
Major and clinically relevant non-major bleeding
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2018.
- Derived from this study: PubMed 33462096van der Veen L, Segers M, van Raay JJ, Gerritsma-Bleeker CL, Brouwer RW, Veeger NJ, van Hulst M. Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study. BMJ Open. 2021 Jan 18;11(1):e040336. doi: 10.1136/bmjopen-2020-040336.
- Derived from this study: PubMed 23355673Veen Lv, van Raay JJ, Gerritsma-Bleeker CL, Veeger NJ, Hulst Mv. Direct treatment comparison of DAbigatran and RIvaroxaban versus NAdroparin in the prevention of venous thromboembolism after total knee arthroplasty surgery: design of a randomised pilot study (DARINA). BMJ Open. 2013 Jan 24;3(1):e002218. doi: 10.1136/bmjopen-2012-002218.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dabigatran, Rivaroxaban and Nadroparin in people with Venous Thromboembolism, run by Martini Hospital Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary safety outcome is the incidence of bleeding events occurring during the study period of 135 days (including follow-up). Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines (time frame: 135 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01431456, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2018.