Venous ThromboembolismPhase 4DISTINCTNCT06581965
inDividual, Targeted thrombosIS Prophylaxis Versus the Standard 'One Size Fits All' Approach in Patients Undergoing Total hIp or Total kNee replaCemenT
A Phase 4 study testing Short duration prophylaxis and Higher intensity and longer duration prophylaxis in people with Venous Thromboembolism and Venous Thromboses, run by Leiden University Medical Center at 13 sites in Netherlands.
Trial summary
After hip or knee replacement all patients receive a standardized treatment with blood thinners, this medication is called thrombosis prophylaxis. However, despite this standard treatment some individuals still develop venous thrombosis (VTE), while others experience bleeding. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism, Venous Thromboses, Pulmonary Embolism
- What is being tested?
- Short duration prophylaxis and Higher intensity and longer duration prophylaxis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10,078 participants
- Where
- 13 sitesNetherlands
- Study dates
- 11 Nov 2024to 1 Feb 2031
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled to undergo an elective total hip arthroplasty or total knee arthroplasty
- Aged 18 years or older
Who cannot join
- Primary arthroplasty for fractures
- Revision surgery
- Hemiarthroplasty
- Pregnancy
- Current use of therapeutic anticoagulant therapy of any type (e.g., LMWH, DOAC, vitamin K antagonist)
- A contraindication for either study drug
Show all 10Show fewer
- Insufficient knowledge of the Dutch language
- Insufficient mental or physical ability to fulfil trial requirements
- Active malignancy (i.e. cancer diagnosis within six months before surgery (excluding basal-cell or squamous-cell carcinoma of the skin), recently recurrent or progressive cancer or any cancer that required anti-cancer treatment within six months before surgery)
- Patients using thrombocyte aggregation inhibitors that cannot be temporarily discontinued at the discretion of their treating physician
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
Netherlands13 sites, 13 recruiting
- Recruiting
OLVG
Amsterdam, North Holland, 1091AC
- Recruiting
Gelre Ziekenhuizen
Apeldoorn, Gelderland, 7334 DZ
- Not yet recruiting
IJsselland Ziekenhuis
Capelle aan den IJssel
- Recruiting
Anna Ziekenhuis
Geldrop, North Brabant, 5564EH
- Recruiting
Zuyderland
Geleen, Limburg, 6162 BG
- Recruiting
Groene Hart Ziekenhuis
Gouda
- Recruiting
Alrijne
Leiderdorp, South Holland, 2353 GA
- Recruiting
Bergman Clinics
Naarden, North Holland, 1411DE
- Recruiting
ZorgSaam
Terneuzen, Zeeland
- Recruiting
Elisabeth-TweeSteden Ziekenhuis
Tilburg, North Brabant, 5022GC
- Recruiting
St. Antonius Ziekenhuis
Utrecht, Utrecht
- Recruiting
Reinier Haga Orthopedisch Centrum
Zoetermeer, South Holland, 2725NA
- Recruiting
Isala ziekenhuis
Zwolle, Overijssel, 8025AB
About this study
Official title: The DISTINCT Trial: inDividual, Targeted thrombosIS Prophylaxis Versus the Standard 'One Size Fits All' Approach in Patients Undergoing Total hIp or Total kNee replaCemenT: a National, Multicenter, Randomized, Multi-arm, Open-label Trial.
After hip or knee replacement all patients receive a standardized treatment with blood thinners, this medication is called thrombosis prophylaxis. However, despite this standard treatment some individuals still develop venous thrombosis (VTE), while others experience bleeding. This indicates that not all patients have the same VTE risk following surgery. Individualizing the amount of thrombosis prophylaxis following surgery might lead to less thrombotic and bleeding events. In this study the investigators individualize the treatment with thrombosis prophylaxis based on the medical history of a patient.
The main questions this study aims to answer are:
Read more
Can thrombosis prophylaxis be shortened in patients with a low VTE risk to decrease the risk of bleeding without increasing the risk of VTE? Does an increase in the dose and duration of thrombosis prophylaxis in patients with a high VTE risk reduce the risk of VTE without inducing an unacceptable risk of bleeds?
Researchers will compare both the shortened treatment in low VTE risk patients and the intensified and extended treatment in high VTE risk patients with the standard treatment to assess the risk of VTE and bleeding in comparison to the standard treatment.
Participants will receive 4 questionnaires to evaluate whether they have experienced a VTE or bleed. For this study no additional hospital visits are necessary.
Read the detailed description
Background
Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are associated with an overall symptomatic venous thromboembolism (VTE) risk of about 1.3% despite the use of prophylactic anticoagulants in all patients. While not preventing all VTEs, the uniform application of anticoagulant prophylaxis is at the same time associated with a major bleeding risk of at least 0.5%. Considering that a large proportion of all patients actually have a low VTE risk, this group is unnecessarily exposed to the burden and risks of thrombosis prophylaxis. On the contrary, some patients with a high VTE risk experience a VTE despite the use of the same prophylactic anticoagulants. These VTE cases could have possibly been prevented by intensified prophylaxis.
Objectives
Overall objective: To study whether the application of a targeted anticoagulation strategy leads to less thrombotic and bleeding complications in this large patient group.
Primary objective DISTINCT study arm 1 : To determine whether in-hospital thrombosis prophylaxis only is as effective compared with the standard thrombosis prophylaxis approach to prevent symptomatic VTE after total knee and hip arthroplasty in patients with a low VTE risk.
Primary objective DISTINCT study arm 2: To determine the incidence of symptomatic VTE after total knee and hip arthroplasty in patients with an intermediate VTE risk.
Primary objective DISTINCT study arm 3: To determine whether intensified thrombosis prophylaxis is more effective and equally safe compared with standard thrombosis prophylaxis to prevent symptomatic VTE in patients with a high VTE risk by comparing symptomatic VTE and bleeding complications.
Methods
The investigators hypothesize that:
- In patients with a low VTE risk the thromboprophylaxis can be safely shortened to in-hospital duration only, without increasing the VTE risk (in comparison with the standard duration). In addition, this will lead to less bleeds.
- In patients with a high VTE risk (individual predicted risk >1.5%), a therapeutic dose of thrombosis prophylaxis for 6 weeks is more effective to prevent symptomatic VTE, in comparison with the standard thromboprophylaxis. In addition, the investigators expect that the benefits of this approach (less symptomatic VTEs) outweigh the induced bleeds.
In the trial participants are allocated to one of three study arms based on the postoperative venous thromboembolism (VTE) risk predicted with the TRiP(plasty) score. (Nemeth, 2024)
- DISTINCT 1 (low VTE risk, <1.0%) will be a randomized study arm.
- DISTINCT 2 (intermediate VTE risk, 1.0%-1.5%) will be an observational study arm.
- DISTINCT 3 (high VTE risk, >1.5%) will be a randomized study arm.
Participants will receive a questionnaire before surgery and 2 weeks, 6 weeks and 3 months after surgery. To assess the outcome measures. Furthermore an additional questionnaire is send 1 year after surgery if the participant experienced a VTE, major bleed or prosthesis infection. This questionnaire is focused on quality of life and joint function. Participants without such an event can be invited to complete this questionnaire as well. No extra hospital visits are needed and the surgery does not change.
Sample size calculations
In DISTINCT study arm 1, the expected 3-month cumulative incidence of symptomatic VTE in the control arm is 0.75%. No risk reduction or increase is anticipated, so the expected risk in the short-duration prophylaxis group is also 0.75%. With a non-inferiority limit set at 1%, a sample size of 3,130 patients is needed to achieve a power of 90%, leading to an aim to include 1,739 patients in each group, totaling 3,478 patients after accounting for a maximum dropout rate of 10%.
For DISTINCT study arm 2, in the intermediate-risk group, the expected cumulative incidence of VTE within 3 months is 1.3%. With a sample size of 2,500, a 95% confidence interval width of 0.9% - 1.7% is expected, ensuring a probability of less than 15% that the upper bound of a two-sided 95% confidence interval will exceed the 2% margin.
In DISTINCT study arm 3, a 3-month cumulative incidence of symptomatic VTE of 2.5% is expected in the control group. With an anticipated relative risk reduction of 50% in the intervention group, a sample size of 3,694 patients is necessary to achieve 80% power. Considering an interim analysis and a slightly stricter statistical significance level at the final analysis, a total of 3,748 patients is required, with 2,050 patients in each arm after accounting for a maximum dropout rate of approximately 9%, totalling 4,100 patients.
Ethics: The study has been approved by the Medical Ethics Committee Leiden Den Haag Delft. All participants will provide informed consent.
- Being tested
- Short duration prophylaxis, Higher intensity and longer duration prophylaxis, Control
- Keywords
- Venous thromboembolism, Prophylaxis, Individualized Medicine, Total hip arthroplasty, Total knee arthroplasty, Randomized controlled trial
- Medical subject headings
- Venous Thromboembolism, Venous Thrombosis, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short duration prophylaxisOther
Only during hospitalization: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guideline "Antitrombotisch beleid". First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use (same type as used for control group).
Higher intensity and longer duration prophylaxisOther
The use of any thrombocyte aggregation inhibitors should be discontinued 5 days prior to surgery. Day 0-2: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guidelines. First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use.
Day 3: Apixaban 5mg b.i.d., continued until 6 weeks after surgery, conditional on the fact that no active bleeding of the surgical wound can be observed. In case of active bleeding, the prophylactic dose of thrombosis prophylaxis is continued. Thereafter, in case no active bleeding has been observed for 24 hours, the 5mg b.i.d. apixaban treatment will be started.
The 5mg b.i.d. apixaban dose will be adjusted to 2.5mg b.i.d. in case of an impaired kidney function (defined as eGFR 10-30ml/min).
ControlOther
Also called Standard treatment
4 weeks: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guidelines. First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use.
| Study group | Role | What they receive |
|---|---|---|
| DISTINCT 1 short duration prophylaxis | Experimental | Patients with a low VTE risk (predicted 3-months postoperative VTE risk <1%) based on the TRiP(plasty) score. (Nemeth, 2024) Receives: Other: Short duration prophylaxis |
| DISTINCT 1 control | Active comparator | Patients with a low VTE risk (predicted 3-months postoperative VTE risk <1%) based on the TRiP(plasty) score. (Nemeth, 2024) Receives: Other: Control |
| DISTINCT 2 observational arm | Other | Patients with an intermediate VTE risk (predicted 3-months postoperative VTE risk ≥1%-≤1.5%) based on the TRiP(plasty) score. (Nemeth, 2024) Receives: Other: Control |
| DISTINCT 3 extended prophylaxis | Experimental | Patients with a high VTE risk (predicted 3-months postoperative VTE risk >1.5%) based on the TRiP(plasty) score. (Nemeth, 2024) Receives: Other: Higher intensity and longer duration prophylaxis |
| DISTINCT 3 control | Active comparator | Patients with a high VTE risk (predicted 3-months postoperative VTE risk >1.5%) based on the TRiP(plasty) score. (Nemeth, 2024) Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Venous thromboembolic events
Number of VTEs in the first 3 months postoperative.
Measured: 90 days postoperative
Major bleeding
Number of major bleeds in the first 3 months postoperative.
Measured: 90 days postoperative
Secondary outcomes (10)
Clinically relevant non major bleeding
Incidence of clinically relevant non-major bleeding
Measured: 90 days postoperative
Impact of events on QALY's
Estimated using the EQ-5D-5L
Measured: 90 days and 1 year postoperative
Healthcare costs
Healthcare costs will be estimated from patient questionnaires at 0, 2, 6, 13 and 52 weeks.
Measured: 90 days and 1 year postoperative
Prosthetic joint infections
Defined according to the European Bone and Joint Infection Society (EBJIS) definition of periprosthetic joint infection described in Bone Joint J 2021;103-B(1):18-25.
Measured: 90 days postoperative
Patient reported quality of life
Measured using the EQ-5D-5L (scored as described in: Value in Health 2016, 19(4), 343-352.)
Measured: 90 days and 1 year postoperative
Patient reported quality of life
Measured using the 36-Item Short Form Health Survey (score 0-100 with a higher score indicating a higher quality of life)
Measured: 1 year postoperative
Patient reported outcome measures
Measured using Oxford Hip score or Ofxord Knee Score depending on the performed surgery. (score 0-100 with a higher score indicating a better outcome)
Measured: 1 year postoperative
Myocardial infarction
Incidence of myocardial infarction
Measured: 90 days postoperative
Ischemic stroke
Incidence of ischemic stroke
Measured: 90 days postoperative
Death
Incidence of death
Measured: 90 days postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study start11 Nov 2024
- Primary completion1 May 2030 (estimated)
- Study completion1 Feb 2031 (estimated)
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.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This trial consists of 3 study arms. DISTINCT 1 (low VTE risk \<1.0%): randomized (2 arms) DISTINCT 2 (intermediate VTE risk 1.0%-1.5%): observational DISTINCT 3 (high VTE risk \>1.5%): randomized (2 arms) Participants will be allocated to a study arm based on their predicted VTE risk which is determined by the TRiP(plasty) score.
- Masking
- None (open label)
- Enrolment
- 10,078 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, B.Nemeth, Leiden University Medical Center
- Investigators
- Banne Nemeth, dr, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06581965
- Sponsor's protocol ID
- P24.031
- Other IDs
- 2023-510186-98-00, U1111-1305-2311, 2023
- Acronym
- DISTINCT
- Status last verified
- Sep 2026
- First submitted
- 25 Aug 2024
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After data collection and data cleaning are finished deidentified data will be registered in a repository and be made available for further research upon reasonable request to the corresponding author.
Publications
Nemeth B, Smeets M, Pedersen AB, Kristiansen EB, Nelissen R, Whyte M, Roberts L, de Lusignan S, le Cessie S, Cannegieter S, Arya R. Development and validation of a clinical prediction model for 90-day venous thromboembolism risk following total hip and total knee arthroplasty: a multinational study. J Thromb Haemost. 2024 Jan;22(1):238-248. doi: 10.1016/j.jtha.2023.09.033. Epub 2023 Nov 22.
PubMed 38030547Kok RY, van Bodegom-Vos L, Ettema HB, Groenwold RHH, van den Hout WB, Huisman MV, Klok FA, Nelissen RGHH, van Rein N, van Veen M, Vehmeijer SBW, Wiegerinck JJI, Cannegieter SC, Nemeth B. Study protocol for the DISTINCT trial: inDividual, targeted thrombosIS prophylaxis versus the standard 'one-size-fits-all' approach in patients undergoing Total hIp or total kNee replaCemenT - a national, multicentre, randomised, multiarm, open-label trial. BMJ Open. 2025 Oct 6;15(10):e101180. doi: 10.1136/bmjopen-2025-101180.
PubMed 41057196
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The DISTINCT Trial: inDividual, Targeted thrombosIS Prophylaxis Versus the Standard 'One Size Fits All' Approach in Patients Undergoing Total hIp or Total kNee replaCemenT: a National, Multicenter, Randomized, Multi-arm, Open-label Trial.
- ClinicalTrials.gov ID
- NCT06581965
- Acronym / sponsor ID
- DISTINCT / P24.031
- Keywords
- Venous thromboembolism, Prophylaxis, Individualized Medicine, Total hip arthroplasty, Total knee arthroplasty, Randomized controlled trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10,078 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- 11 Nov 2024 (actual)
- Primary completion
- 1 May 2030 (estimated)
- Study completion
- 1 Feb 2031 (estimated)
- First posted
- 3 Sep 2024 (actual)
- 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.
After hip or knee replacement all patients receive a standardized treatment with blood thinners, this medication is called thrombosis prophylaxis. However, despite this standard treatment some individuals still develop venous thrombosis (VTE), while others experience bleeding. This indicates that not all patients have the same VTE risk following surgery. Individualizing the amount of thrombosis prophylaxis following surgery might lead to less thrombotic and bleeding events. In this study the investigators individualize the treatment with thrombosis prophylaxis based on the medical history of a patient.
The main questions this study aims to answer are:
Can thrombosis prophylaxis be shortened in patients with a low VTE risk to decrease the risk of bleeding without increasing the risk of VTE? Does an increase in the dose and duration of thrombosis prophylaxis in patients with a high VTE risk reduce the risk of VTE without inducing an unacceptable risk of bleeds?
Researchers will compare both the shortened treatment in low VTE risk patients and the intensified and extended treatment in high VTE risk patients with the standard treatment to assess the risk of VTE and bleeding in comparison to the standard treatment.
Participants will receive 4 questionnaires to evaluate whether they have experienced a VTE or bleed. For this study no additional hospital visits are necessary.
Detailed description
Background
Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are associated with an overall symptomatic venous thromboembolism (VTE) risk of about 1.3% despite the use of prophylactic anticoagulants in all patients. While not preventing all VTEs, the uniform application of anticoagulant prophylaxis is at the same time associated with a major bleeding risk of at least 0.5%. Considering that a large proportion of all patients actually have a low VTE risk, this group is unnecessarily exposed to the burden and risks of thrombosis prophylaxis. On the contrary, some patients with a high VTE risk experience a VTE despite the use of the same prophylactic anticoagulants. These VTE cases could have possibly been prevented by intensified prophylaxis.
Objectives
Overall objective: To study whether the application of a targeted anticoagulation strategy leads to less thrombotic and bleeding complications in this large patient group.
Primary objective DISTINCT study arm 1 : To determine whether in-hospital thrombosis prophylaxis only is as effective compared with the standard thrombosis prophylaxis approach to prevent symptomatic VTE after total knee and hip arthroplasty in patients with a low VTE risk.
Primary objective DISTINCT study arm 2: To determine the incidence of symptomatic VTE after total knee and hip arthroplasty in patients with an intermediate VTE risk.
Primary objective DISTINCT study arm 3: To determine whether intensified thrombosis prophylaxis is more effective and equally safe compared with standard thrombosis prophylaxis to prevent symptomatic VTE in patients with a high VTE risk by comparing symptomatic VTE and bleeding complications.
Methods
The investigators hypothesize that:
- In patients with a low VTE risk the thromboprophylaxis can be safely shortened to in-hospital duration only, without increasing the VTE risk (in comparison with the standard duration). In addition, this will lead to less bleeds.
- In patients with a high VTE risk (individual predicted risk >1.5%), a therapeutic dose of thrombosis prophylaxis for 6 weeks is more effective to prevent symptomatic VTE, in comparison with the standard thromboprophylaxis. In addition, the investigators expect that the benefits of this approach (less symptomatic VTEs) outweigh the induced bleeds.
In the trial participants are allocated to one of three study arms based on the postoperative venous thromboembolism (VTE) risk predicted with the TRiP(plasty) score. (Nemeth, 2024)
- DISTINCT 1 (low VTE risk, <1.0%) will be a randomized study arm.
- DISTINCT 2 (intermediate VTE risk, 1.0%-1.5%) will be an observational study arm.
- DISTINCT 3 (high VTE risk, >1.5%) will be a randomized study arm.
Participants will receive a questionnaire before surgery and 2 weeks, 6 weeks and 3 months after surgery. To assess the outcome measures. Furthermore an additional questionnaire is send 1 year after surgery if the participant experienced a VTE, major bleed or prosthesis infection. This questionnaire is focused on quality of life and joint function. Participants without such an event can be invited to complete this questionnaire as well. No extra hospital visits are needed and the surgery does not change.
Sample size calculations
In DISTINCT study arm 1, the expected 3-month cumulative incidence of symptomatic VTE in the control arm is 0.75%. No risk reduction or increase is anticipated, so the expected risk in the short-duration prophylaxis group is also 0.75%. With a non-inferiority limit set at 1%, a sample size of 3,130 patients is needed to achieve a power of 90%, leading to an aim to include 1,739 patients in each group, totaling 3,478 patients after accounting for a maximum dropout rate of 10%.
For DISTINCT study arm 2, in the intermediate-risk group, the expected cumulative incidence of VTE within 3 months is 1.3%. With a sample size of 2,500, a 95% confidence interval width of 0.9% - 1.7% is expected, ensuring a probability of less than 15% that the upper bound of a two-sided 95% confidence interval will exceed the 2% margin.
In DISTINCT study arm 3, a 3-month cumulative incidence of symptomatic VTE of 2.5% is expected in the control group. With an anticipated relative risk reduction of 50% in the intervention group, a sample size of 3,694 patients is necessary to achieve 80% power. Considering an interim analysis and a slightly stricter statistical significance level at the final analysis, a total of 3,748 patients is required, with 2,050 patients in each arm after accounting for a maximum dropout rate of approximately 9%, totalling 4,100 patients.
Ethics: The study has been approved by the Medical Ethics Committee Leiden Den Haag Delft. All participants will provide informed consent.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- This trial consists of 3 study arms. DISTINCT 1 (low VTE risk <1.0%): randomized (2 arms) DISTINCT 2 (intermediate VTE risk 1.0%-1.5%): observational DISTINCT 3 (high VTE risk >1.5%): randomized (2 arms) Participants will be allocated to a study arm based on their predicted VTE risk which is determined by the TRiP(plasty) score.
| Arm | Type | Receives |
|---|---|---|
| DISTINCT 1 short duration prophylaxis | Experimental | Other: Short duration prophylaxisPatients with a low VTE risk (predicted 3-months postoperative VTE risk <1%) based on the TRiP(plasty) score. (Nemeth, 2024) |
| DISTINCT 1 control | Active comparator | Other: ControlPatients with a low VTE risk (predicted 3-months postoperative VTE risk <1%) based on the TRiP(plasty) score. (Nemeth, 2024) |
| DISTINCT 2 observational arm | Other | Other: ControlPatients with an intermediate VTE risk (predicted 3-months postoperative VTE risk ≥1%-≤1.5%) based on the TRiP(plasty) score. (Nemeth, 2024) |
| DISTINCT 3 extended prophylaxis | Experimental | Other: Higher intensity and longer duration prophylaxisPatients with a high VTE risk (predicted 3-months postoperative VTE risk >1.5%) based on the TRiP(plasty) score. (Nemeth, 2024) |
| DISTINCT 3 control | Active comparator | Other: ControlPatients with a high VTE risk (predicted 3-months postoperative VTE risk >1.5%) based on the TRiP(plasty) score. (Nemeth, 2024) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Scheduled to undergo an elective total hip arthroplasty or total knee arthroplasty
- Aged 18 years or older
Key exclusion criteria (10 listed)
- Primary arthroplasty for fractures
- Revision surgery
- Hemiarthroplasty
- Pregnancy
- Current use of therapeutic anticoagulant therapy of any type (e.g., LMWH, DOAC, vitamin K antagonist)
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 |
|---|---|---|
| Short duration prophylaxisOnly during hospitalization: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guideline "Antitrombotisch beleid". First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use (same type as used for control group). | Other | DISTINCT 1 short duration prophylaxis |
| Higher intensity and longer duration prophylaxisThe use of any thrombocyte aggregation inhibitors should be discontinued 5 days prior to surgery. Day 0-2: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guidelines. First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use. Day 3: Apixaban 5mg b.i.d., continued until 6 weeks after surgery, conditional on the fact that no active bleeding of the surgical wound can be observed. In case of active bleeding, the prophylactic dose of thrombosis prophylaxis is continued. Thereafter, in case no active bleeding has been observed for 24 hours, the 5mg b.i.d. apixaban treatment will be started. The 5mg b.i.d. apixaban dose will be adjusted to 2.5mg b.i.d. in case of an impaired kidney function (defined as eGFR 10-30ml/min). | Other | DISTINCT 3 extended prophylaxis |
| ControlAlso: Standard treatment4 weeks: any type of LMWH or DOAC in a prophylactic dose as approved by the Dutch guidelines. First dose of LMWH within 6-24h following surgery. First dose of apixaban within 12-24h following surgery. First dose of rivaroxaban 6-10h following surgery. First dose of dabigatran within 1-4h following surgery. The applied type of anticoagulant is according to the local standard use. | Other | DISTINCT 1 control, DISTINCT 2 observational arm, DISTINCT 3 control |
Primary outcome
Venous thromboembolic events
Time frame: 90 days postoperative
Number of VTEs in the first 3 months postoperative.
Major bleeding
Time frame: 90 days postoperative
Number of major bleeds in the first 3 months postoperative.
10 secondary outcomes
Clinically relevant non major bleeding
Time frame: 90 days postoperative
Impact of events on QALY's
Time frame: 90 days and 1 year postoperative
Healthcare costs
Time frame: 90 days and 1 year postoperative
Prosthetic joint infections
Time frame: 90 days postoperative
Patient reported quality of life
Time frame: 90 days and 1 year postoperative
Patient reported quality of life
Time frame: 1 year postoperative
Patient reported outcome measures
Time frame: 1 year postoperative
Myocardial infarction
Time frame: 90 days postoperative
Ischemic stroke
Time frame: 90 days postoperative
Death
Time frame: 90 days postoperative
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
- Background: PubMed 38030547Nemeth B, Smeets M, Pedersen AB, Kristiansen EB, Nelissen R, Whyte M, Roberts L, de Lusignan S, le Cessie S, Cannegieter S, Arya R. Development and validation of a clinical prediction model for 90-day venous thromboembolism risk following total hip and total knee arthroplasty: a multinational study. J Thromb Haemost. 2024 Jan;22(1):238-248. doi: 10.1016/j.jtha.2023.09.033. Epub 2023 Nov 22.
- Derived from this study: PubMed 41057196Kok RY, van Bodegom-Vos L, Ettema HB, Groenwold RHH, van den Hout WB, Huisman MV, Klok FA, Nelissen RGHH, van Rein N, van Veen M, Vehmeijer SBW, Wiegerinck JJI, Cannegieter SC, Nemeth B. Study protocol for the DISTINCT trial: inDividual, targeted thrombosIS prophylaxis versus the standard 'one-size-fits-all' approach in patients undergoing Total hIp or total kNee replaCemenT - a national, multicentre, randomised, multiarm, open-label trial. BMJ Open. 2025 Oct 6;15(10):e101180. doi: 10.1136/bmjopen-2025-101180.
- Individual participant dataSharing planned: Yes. After data collection and data cleaning are finished deidentified data will be registered in a repository and be made available for further research upon reasonable request to the corresponding author.
Related trials for Venous Thromboembolism
RecruitingPhase 3
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults
Venous Thromboembolism (VTE)
RecruitingPhase 3
Treatment and Secondary Prevention of Venous Thromboembolism (VTE) in Adult Participants With Solid and Hematologic Cancers
Venous Thromboembolism (VTE)
RecruitingPhase 3
REGN7508 in Adult Participants for Prevention of Cancer-Associated Thrombosis
Cancer-Associated Thrombosis (CAT)
RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
Symptomatic Venous Thromboembolism (VTE)
Recruiting
DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis
Venous Thromboembolism, Deep Venous Thrombosis
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.
Banne Nemeth, dr principal investigator
Leiden University Medical Center
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Short duration prophylaxis and Higher intensity and longer duration prophylaxis in people with Venous Thromboembolism and Venous Thromboses, run by Leiden University Medical Center at 13 sites 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 2 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: looking for participants now, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Banne Nemeth, dr (+31715264037, B.Nemeth@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous thromboembolic events (time frame: 90 days postoperative). The study lists 2 primary outcomes in all. 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 NCT06581965, 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 8 Sep 2026.