A Phase 4 interventional study of Short duration prophylaxis and Higher intensity and longer duration prophylaxis in Venous Thromboembolism, Venous Thromboses and Pulmonary Embolism, sponsored by Leiden University Medical Center. Recruiting at 13 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.
Sponsored by Leiden University Medical Center · Phase 4, Interventional, and Prevention
Among 50 studies in Venous Thromboembolism with a site in Netherlands — 4 open to participants now, 5 under way, 1 of them phase 3. Venous Thromboembolism · Netherlands.
Among the 50 studies in Venous Thromboembolism with a site in Netherlands, this one has the largest planned enrollment of the 36 interventional ones, is the only one that started in 2024, is one of 6 in phase 4, and was the 50th registered.
712 studies on the registry are indexed under Venous Thromboembolism; 146 are open to participants now.
This study's planned enrollment of 10,078 is above the median of 240 across 401 interventional studies indexed under Venous Thromboembolism.
Browse Venous Thromboembolism studies →4 of the 50 studies in Venous Thromboembolism with a site in Netherlands are open now, in 10 countries. Each count lists the studies.
Of the 113 Venous Thromboembolism studies recruiting now, 90 (80%) set no upper age limit and 13 (12%) stop at 75 or younger; 9 take children under 18; 10 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →50 studies; the count open now beside each. This study's row is marked.
First in 2002; this study’s year is marked. 1 started in 2024.
Median enrollment 924 across the 36 interventional studies, 586 across the 14 observational. Of the 44 that completed or were terminated, 19 (43%) have results posted.
30 of 50 have an industry lead sponsor. The 10 most frequent:
Leiden University Medical Center is the lead sponsor of 334 studies on the registry; 110 are open to participants now.
Leiden University Medical Center has 3 studies filed under Venous Thromboembolism — fewer than ten, so there is no comparison to draw.
1 of the studies in Venous Thromboembolism with a site in Netherlands that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06087952Leiden University Medical CenterLeiden Thrombosis Recurrence Risk Prevention | 2027-06-01 |
Among the 50 studies in Venous Thromboembolism with a site in Netherlands, from their registry updates:
Nothing recorded among them since 2026-09-25.
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.
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 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)
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with a low VTE risk (predicted 3-months postoperative VTE risk \<1%) based on the TRiP(plasty) score. (Nemeth, 2024)
Other: Short duration prophylaxis
Patients with a low VTE risk (predicted 3-months postoperative VTE risk \<1%) based on the TRiP(plasty) score. (Nemeth, 2024)
Other: Control
Patients with an intermediate VTE risk (predicted 3-months postoperative VTE risk ≥1%-≤1.5%) based on the TRiP(plasty) score. (Nemeth, 2024)
Other: Control
Patients with a high VTE risk (predicted 3-months postoperative VTE risk \>1.5%) based on the TRiP(plasty) score. (Nemeth, 2024)
Other: Higher intensity and longer duration prophylaxis
Patients with a high VTE risk (predicted 3-months postoperative VTE risk \>1.5%) based on the TRiP(plasty) score. (Nemeth, 2024)
Other: Control
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).
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).
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.
Also known as: Standard treatment
Venous thromboembolic events
Number of VTEs in the first 3 months postoperative.
Time frame: 90 days postoperative
Major bleeding
Number of major bleeds in the first 3 months postoperative.
Time frame: 90 days postoperative
Clinically relevant non major bleeding
Incidence of clinically relevant non-major bleeding
Time frame: 90 days postoperative
Impact of events on QALY's
Estimated using the EQ-5D-5L
Time frame: 90 days and 1 year postoperative
Healthcare costs
Healthcare costs will be estimated from patient questionnaires at 0, 2, 6, 13 and 52 weeks.
Time frame: 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.
Time frame: 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.)
Time frame: 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)
Time frame: 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)
Time frame: 1 year postoperative
Myocardial infarction
Incidence of myocardial infarction
Time frame: 90 days postoperative
Ischemic stroke
Incidence of ischemic stroke
Time frame: 90 days postoperative
Death
Incidence of death
Time frame: 90 days postoperative
Plan to share: 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.
Started Nov 2024 (actual). Primary completion is estimated for May 2030, 65 months after the start.
Of 34 phase 4 interventional studies under Venous Thromboembolism, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 88. This study's planned 65 months is above that.
How these figures are worked out, and which studies are left out of them.
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