NCT06087952

Leiden Thrombosis Recurrence Risk Prevention

Leiden Thrombosis Recurrence Risk Prevention: Tailored Treatment After a First Venous Thromboembolism

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 608 (estimated)
• Sponsor: Leiden University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to evaluate tailored duration of long-term anticoagulant treatment after a first venous thromboembolism based on individualized risk assessments of recurrent VTE and major bleeding risks. Participants will be asked to fill in a questionnaire and take a buccal swab, which are used for an individual estimation of the risks of recurrent VTE and bleeding. Based on these risks a treatment advise will be made, or randomised in a subgroup of patients.

Detailed description

Background: Patients with a first venous thromboembolism (VTE) are at risk of recurrence. A recurrent VTE can be prevented by prolonged anticoagulant therapy, but this may come at the cost of major bleeding. The L-TRRiP and VTE-BLEED prediction scores have been developed to classify the risk of recurrent VTE (low, intermediate, high) and major bleeding (low vs high), respectively. However, their combined use in finding the optimal balance to minimize both long-term risks is unclear. Aims: To evaluate tailored duration of long-term anticoagulant treatment based on individualized risk assessments of recurrent VTE and major bleeding risks. Methods: The L-TRRiP study is a multicenter, open-label, cohort based randomized controlled trial in which patients with a first VTE will be included. For each patient the risk of recurrent VTE (low, medium, high) and major bleeding (low, high) will be determined using the L-TRRiP and VTE-BLEED prediction scores, respectively. After three months of initial anticoagulant therapy, patients with a low recurrent VTE risk (\<6% in 2 years) will discontinue anticoagulants, whereas patients with a high recurrent VTE risk(\>14% in 2 years) and low major bleeding risk will continue. The other groups, with unclear benefit of prolonged treatment, will be randomized to continue or discontinue anticoagulants. Patients will be followed for at least two years, during which they will be asked to fill in a questionnaire every 3 months during the first two years, followed by a questionnaire once a year for the remaining duration of the study (i.e., 2 years after inclusion of the last participant; which is expected to be in 2027). The total follow-up duration is therefore expected to vary between 2 to 6 years. The follow-up questionnaires are used to screen for potential outcomes (including recurrent VTE and bleeding), and includes the EQ-5D-5L to assess quality of life, the Post VTE functional status scale to assess functional outcomes and the Medical Consumption and Productivity Costs Questionnaire to asses cost-effectiveness. In case of a potential outcome additional information is retrieved from the medical record for adjudication. The clinical outcomes will be evaluated and classified by an independent committee blinded for treatment allocation. Sample size: The sample size of this study is based on the randomized part of the study. To demonstrate a 7% difference in the combined endpoint (i.e., 10.6% vs 3.6%) with an alpha of 0.05 and a power of 90%, a sample size of 552 subjects for the randomized part of the study is required. Taking into account a drop-out rate of 10%, the aim is to include 608 patients in the randomized part of the study. After inclusion of 608 randomized patients, inclusion will stop. Based on the derivation studies it is expected the randomized group will form about 40% of the total included population, in which case the estimated total number of included patients will be 1600. Of note, this total number may change depending on the final proportion of the randomized group. Ethics: The study has been approved by the Medical Ethics Committee Leiden Den Haag Delft. All participants will provide informed consent.

Conditions

• Venous Thromboembolism
• Venous Thromboses
• Pulmonary Embolism
• Deep Vein Thrombosis

Interventions

Type	Name	Description
OTHER	Randomised treatment advice (discontinue vs continue after 3 months)	Randomisation to continue or discontinue anticoagulant therapy in 1:1 ratio stratified on risk category of L-TRRiP and VTE-BLEED score
DIAGNOSTIC_TEST	VTE-BLEED score	Predict bleeding risk during extended anticoagulant treatment (high or low) using the VTE-BLEED score
DIAGNOSTIC_TEST	L-TRRiP score	Predict VTE recurrence risk after anticoagulant discontinuation (high, intermediate or low) using the L-TRRiP score
OTHER	Advise to continue anticoagulant treatment after 3 months	Advise to continue anticoagulant treatment after 3 months for patients with high VTE recurrence and low bleeding risk
OTHER	Advise to discontinue anticoagulant treatment after 3 months	Advise to discontinue anticoagulant treatment after 3 months for patients with low VTE recurrence risk

Timeline

• Start date: 2021-06-18
• Primary completion: 2027-06-01
• Completion: 2027-06-01
• First posted: 2023-10-18
• Last updated: 2026-02-20

Locations

19 sites across 1 country: Netherlands