Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06581965
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-25
Brief Title:
inDividual Targeted thrombosIS Prophylaxis Versus the Standard One Size Fits All Approach in Patients Undergoing Total hIp or Total kNee replaCemenT
Sponsor:
None
Organization:
None
Study Overview
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
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DISTINCT
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
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 13 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 05 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 15 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 TRiPplasty score Nemeth 2024
DISTINCT 1 low VTE risk 10 will be a randomized study arm
DISTINCT 2 intermediate VTE risk 10-15 will be an observational study arm
DISTINCT 3 high VTE risk 15 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 075 No risk reduction or increase is anticipated so the expected risk in the short-duration prophylaxis group is also 075 With a non-inferiority limit set at 1 a sample size of 3130 patients is needed to achieve a power of 90 leading to an aim to include 1739 patients in each group totaling 3478 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 13 With a sample size of 2500 a 95 confidence interval width of 09 - 17 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 25 is expected in the control group With an anticipated relative risk reduction of 50 in the intervention group a sample size of 3694 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 3748 patients is required with 2050 patients in each arm after accounting for a maximum dropout rate of approximately 9 totalling 4100 patients
Ethics The study has been approved by the Medical Ethics Committee Leiden Den Haag Delft All participants will provide informed consent
Total hip arthroplasty THA and total knee arthroplasty TKA are associated with an overall symptomatic venous thromboembolism VTE risk of about 13 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 05 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 15 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 TRiPplasty score Nemeth 2024
DISTINCT 1 low VTE risk 10 will be a randomized study arm
DISTINCT 2 intermediate VTE risk 10-15 will be an observational study arm
DISTINCT 3 high VTE risk 15 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 075 No risk reduction or increase is anticipated so the expected risk in the short-duration prophylaxis group is also 075 With a non-inferiority limit set at 1 a sample size of 3130 patients is needed to achieve a power of 90 leading to an aim to include 1739 patients in each group totaling 3478 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 13 With a sample size of 2500 a 95 confidence interval width of 09 - 17 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 25 is expected in the control group With an anticipated relative risk reduction of 50 in the intervention group a sample size of 3694 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 3748 patients is required with 2050 patients in each arm after accounting for a maximum dropout rate of approximately 9 totalling 4100 patients
Ethics The study has been approved by the Medical Ethics Committee Leiden Den Haag Delft All participants will provide informed consent
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None