InDividual, Targeted ThrombosIS Prophylaxis Versus the Standard 'one Size Fits All' Approach in Patients Undergoing Total HIp or Total KNee ReplaCemenT
- Conditions
- Venous ThromboembolismVenous ThrombosesPulmonary EmbolismDeep Vein Thrombosis
- Interventions
- Other: Short duration prophylaxisOther: ControlOther: Higher intensity and longer duration prophylaxis
- Registration Number
- NCT06581965
- Lead Sponsor
- Leiden University Medical Center
- Brief 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. 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:
1. 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.
2. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10078
- Scheduled to undergo an elective total hip arthroplasty or total knee arthroplasty
- Aged 18 years or older
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DISTINCT 1 short duration prophylaxis Short duration prophylaxis Patients with a low VTE risk (predicted 3-months postoperative VTE risk \<1%) based on the TRiP(plasty) score. (Nemeth, 2024) DISTINCT 1 control Control Patients with a low VTE risk (predicted 3-months postoperative VTE risk \<1%) based on the TRiP(plasty) score. (Nemeth, 2024) DISTINCT 2 observational arm Control Patients 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 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) DISTINCT 3 control Control Patients with a high VTE risk (predicted 3-months postoperative VTE risk \>1.5%) based on the TRiP(plasty) score. (Nemeth, 2024)
- Primary Outcome Measures
Name Time Method Venous thromboembolic events 90 days postoperative Number of VTEs in the first 3 months postoperative.
Major bleeding 90 days postoperative Number of major bleeds in the first 3 months postoperative.
- Secondary Outcome Measures
Name Time Method Clinically relevant non major bleeding 90 days postoperative Incidence of clinically relevant non-major bleeding
Impact of events on QALY's 90 days and 1 year postoperative Estimated using the EQ-5D-5L
Healthcare costs 90 days and 1 year postoperative Healthcare costs will be estimated from patient questionnaires at 0, 2, 6, 13 and 52 weeks.
Prosthetic joint infections 90 days postoperative 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.
Patient reported quality of life 1 year postoperative Measured using the 36-Item Short Form Health Survey (score 0-100 with a higher score indicating a higher quality of life)
Patient reported outcome measures 1 year postoperative 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)
Myocardial infarction 90 days postoperative Incidence of myocardial infarction
Ischemic stroke 90 days postoperative Incidence of ischemic stroke
Death 90 days postoperative Incidence of death
Trial Locations
- Locations (6)
Elisabeth-TweeSteden Ziekenhuis
🇳🇱Tilburg, Noord-Brabant, Netherlands
Isala ziekenhuis
🇳🇱Zwolle, Overijssel, Netherlands
Reinier Haga Orthopedisch Centrum
🇳🇱Zoetermeer, Zuid-Holland, Netherlands
Anna Ziekenhuis
🇳🇱Geldrop, Noord-Brabant, Netherlands
OLVG
🇳🇱Amsterdam, Noord-Holland, Netherlands
Bergman Clinics
🇳🇱Naarden, Noord-Holland, Netherlands