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.