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Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP)

Primary Purpose

Venous Thromboembolism, Venous Thromboses, Pulmonary Embolism

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Randomised treatment advice (discontinue vs continue after 3 months)
VTE-BLEED score
L-TRRiP score
Advise to continue anticoagulant treatment after 3 months
Advise to discontinue anticoaguant treatment after 3 months
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Venous Thromboembolism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provision of informed consent prior to any study specific procedures. Be diagnosed with a first confirmed symptomatic deep vein thrombosis (including distal vein thrombosis, in Dutch: 'kuitvenetrombose') or pulmonary embolism with an indication for treatment with anticoagulant therapy for at least 3 months as prescribed by their treating physician. Be aged 18 years or above. Exclusion Criteria: Patients with active cancer (i.e. cancer diagnosis within six months before VTE (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 the venous thromboembolism was diagnosed) or antiphospholipid syndrome Patients who need to continue anticoagulant treatment for another indication (e.g. atrial fibrillation). Patients with a strong indication for long-term antiplatelet therapy despite oral anticoagulation (e.g. those with recent STEMI) Patients with COVID-19 associated VTE (hospital admission because of COVID-19 <3 months before the VTE) or vaccine-induced immune thrombotic thrombocytopenia (VITT) Patients in whom the risk of bleeding is deemed extremely high by the treating physician, necessitating discontinuation of anticoagulant treatment for the first VTE after the initial 3 months or even during the initial 3 months.

Sites / Locations

  • Leiden University Medical CenterRecruiting
  • Amsterdam Medical Center, location AMCRecruiting
  • Wilhelmina ZiekenhuisRecruiting
  • Rode Kruis ZiekenhuisRecruiting
  • Amphia ZiekenhuisRecruiting
  • Haaglanden Medisch CentrumRecruiting
  • HagaZiekenhuisRecruiting
  • Nij Smellinghe ZiekenhuisRecruiting
  • Ziekenhuis Gelderse ValleiRecruiting
  • Admiraal de Ruyter ZiekenhuisRecruiting
  • Groene Hart ZiekenhuisRecruiting
  • Martini ZiekenhuisRecruiting
  • University Medical Center GroningenRecruiting
  • Radboud University Medical CenterRecruiting
  • Ikazia ZiekenhuisRecruiting
  • DiakonessenhuisRecruiting
  • Isala KliniekenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

Continue anticoagulation

Discontinue anticoagulation

Randomised to continue anticoagulation

Randomised to discontinue anticoagulation

Arm Description

Patients with high recurrent VTE risk and low major bleeding risks are advised to continue anticoagulant therapy.

Patients with low recurrent VTE risk are advised to discontinue anticoagulant therapy.

Patients with intermediate recurrent VTE risk or high recurrent VTE risk and high major bleeding risk are randomised to continue or discontinue anticoagulant therapy.

Patients with intermediate recurrent VTE risk or high recurrent VTE risk and high major bleeding risk are randomised to continue or discontinue anticoagulant therapy.

Outcomes

Primary Outcome Measures

Recurrent VTE and major bleeding
Incidence of the combined endpoint recurrent VTE and major bleeding in the randomised arms

Secondary Outcome Measures

Primary outcome weighted for quality of life (EQ-5D-5L)
Recurrent VTE and major bleeding weighted for the impact on quality of life as measured by the EQ-5D-5L
Primary outcome weighted for functional status (PFVS)
Recurrent VTE and major bleeding weighted for the impact on functional limitations as measured by the Post-VTE functional status scale (PFVS) a grade for functional outcomes after a VTE, ranging from grade 0 (no functional limitations, symptoms, pain or anxiety) to grade 4 (severe functional limitations, requiring assistance in activities of daily living) or death..
Recurrent VTE and major bleeding in non-randomised arms
Incidence of the combined endpoint in the non-randomised arms
Cost-effectiveness
For the analysis of cost-effectiveness health care costs and productivity losses will be measured every 3 months during follow-up by the Medical Consumption Questionnaire and Productivity Costs Questionnaire from the institute for Medical Technology Assessment. Health care costs will be calculated using Dutch standard prices for economic evaluations. Absence from work will be valued with friction cost method. Quality Adjusted Life Years (QALYs) will be assessed using the EQ-5D-5L score, which is taken every 3 months during follow-up, using the area-under-the-curve approach. Economic evaluation will consists of both a study-based cost-effectiveness analysis (cost per event) as well as cost-utility analysis with a lifetime horizon (costs per QALY).
Natural course of recovery
Natural course of recovery with regard to long-term functional limitations, measured by post VTE functional status scale every 3 months through the follow-up period of 2 years. Using the post VTE functional status scale (PFVS) a grade for functional outcomes after a VTE, ranging from grade 0 (no functional limitations, symptoms, pain or anxiety) to grade 4 (severe functional limitations, requiring assistance in activities of daily living) or death.
Clinically relevant non-major bleeding
Incidence of clinically relevant non-major bleeding in different study arms

Full Information

First Posted
July 25, 2023
Last Updated
October 17, 2023
Sponsor
Leiden University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT06087952
Brief Title
Leiden Thrombosis Recurrence Risk Prevention
Acronym
L-TRRiP
Official Title
Leiden Thrombosis Recurrence Risk Prevention: Tailored Treatment After a First Venous Thromboembolism
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 18, 2021 (Actual)
Primary Completion Date
June 1, 2027 (Anticipated)
Study Completion Date
June 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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 two years, during which they will be asked to fill in a questionnaire every 3 months. These questionnaire is 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism, Venous Thromboses, Pulmonary Embolism, Deep Vein Thrombosis

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Patients with low recurrent VTE risk are advised to stop anticoagulant therapy. Patients with high recurrent VTE risk and low bleeding risk are advised to continue anticoagulant therapy. Patients with intermediate recurrent VTE risk, or high recurrent VTE risk and high bleeding risk are randomised to stop or continue anticoagulant therapy.
Masking
None (Open Label)
Masking Description
Blinded endpoint adjudication
Allocation
Randomized
Enrollment
608 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Continue anticoagulation
Arm Type
Other
Arm Description
Patients with high recurrent VTE risk and low major bleeding risks are advised to continue anticoagulant therapy.
Arm Title
Discontinue anticoagulation
Arm Type
Other
Arm Description
Patients with low recurrent VTE risk are advised to discontinue anticoagulant therapy.
Arm Title
Randomised to continue anticoagulation
Arm Type
Other
Arm Description
Patients with intermediate recurrent VTE risk or high recurrent VTE risk and high major bleeding risk are randomised to continue or discontinue anticoagulant therapy.
Arm Title
Randomised to discontinue anticoagulation
Arm Type
Other
Arm Description
Patients with intermediate recurrent VTE risk or high recurrent VTE risk and high major bleeding risk are randomised to continue or discontinue anticoagulant therapy.
Intervention Type
Other
Intervention Name(s)
Randomised treatment advice (discontinue vs continue after 3 months)
Intervention Description
Randomisation to continue or discontinue anticoagulant therapy in 1:1 ratio stratified on risk category of L-TRRiP and VTE-BLEED score
Intervention Type
Diagnostic Test
Intervention Name(s)
VTE-BLEED score
Intervention Description
Predict bleeding risk during extended anticoagulant treatment (high or low) using the VTE-BLEED score
Intervention Type
Diagnostic Test
Intervention Name(s)
L-TRRiP score
Intervention Description
Predict VTE recurrence risk after anticoagulant discontinuation (high, intermediate or low) using the L-TRRiP score
Intervention Type
Other
Intervention Name(s)
Advise to continue anticoagulant treatment after 3 months
Intervention Description
Advise to continue anticoagulant treatment after 3 months for patients with high VTE recurrence and low bleeding risk
Intervention Type
Other
Intervention Name(s)
Advise to discontinue anticoaguant treatment after 3 months
Intervention Description
Advise to discontinue anticoagulant treatment after 3 months for patients with low VTE recurrence risk
Primary Outcome Measure Information:
Title
Recurrent VTE and major bleeding
Description
Incidence of the combined endpoint recurrent VTE and major bleeding in the randomised arms
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Primary outcome weighted for quality of life (EQ-5D-5L)
Description
Recurrent VTE and major bleeding weighted for the impact on quality of life as measured by the EQ-5D-5L
Time Frame
2 years
Title
Primary outcome weighted for functional status (PFVS)
Description
Recurrent VTE and major bleeding weighted for the impact on functional limitations as measured by the Post-VTE functional status scale (PFVS) a grade for functional outcomes after a VTE, ranging from grade 0 (no functional limitations, symptoms, pain or anxiety) to grade 4 (severe functional limitations, requiring assistance in activities of daily living) or death..
Time Frame
2 years
Title
Recurrent VTE and major bleeding in non-randomised arms
Description
Incidence of the combined endpoint in the non-randomised arms
Time Frame
2 years
Title
Cost-effectiveness
Description
For the analysis of cost-effectiveness health care costs and productivity losses will be measured every 3 months during follow-up by the Medical Consumption Questionnaire and Productivity Costs Questionnaire from the institute for Medical Technology Assessment. Health care costs will be calculated using Dutch standard prices for economic evaluations. Absence from work will be valued with friction cost method. Quality Adjusted Life Years (QALYs) will be assessed using the EQ-5D-5L score, which is taken every 3 months during follow-up, using the area-under-the-curve approach. Economic evaluation will consists of both a study-based cost-effectiveness analysis (cost per event) as well as cost-utility analysis with a lifetime horizon (costs per QALY).
Time Frame
Up to 2 years
Title
Natural course of recovery
Description
Natural course of recovery with regard to long-term functional limitations, measured by post VTE functional status scale every 3 months through the follow-up period of 2 years. Using the post VTE functional status scale (PFVS) a grade for functional outcomes after a VTE, ranging from grade 0 (no functional limitations, symptoms, pain or anxiety) to grade 4 (severe functional limitations, requiring assistance in activities of daily living) or death.
Time Frame
Up to 2 years
Title
Clinically relevant non-major bleeding
Description
Incidence of clinically relevant non-major bleeding in different study arms
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of informed consent prior to any study specific procedures. Be diagnosed with a first confirmed symptomatic deep vein thrombosis (including distal vein thrombosis, in Dutch: 'kuitvenetrombose') or pulmonary embolism with an indication for treatment with anticoagulant therapy for at least 3 months as prescribed by their treating physician. Be aged 18 years or above. Exclusion Criteria: Patients with active cancer (i.e. cancer diagnosis within six months before VTE (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 the venous thromboembolism was diagnosed) or antiphospholipid syndrome Patients who need to continue anticoagulant treatment for another indication (e.g. atrial fibrillation). Patients with a strong indication for long-term antiplatelet therapy despite oral anticoagulation (e.g. those with recent STEMI) Patients with COVID-19 associated VTE (hospital admission because of COVID-19 <3 months before the VTE) or vaccine-induced immune thrombotic thrombocytopenia (VITT) Patients in whom the risk of bleeding is deemed extremely high by the treating physician, necessitating discontinuation of anticoagulant treatment for the first VTE after the initial 3 months or even during the initial 3 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Suzanne Cannegieter, MD, PhD
Phone
+31715261508
Email
s.c.cannegieter@lumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suzanne Cannegieter, MD, PhD
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
State/Province
South-Holland
ZIP/Postal Code
2333 ZA
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Amsterdam Medical Center, location AMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Wilhelmina Ziekenhuis
City
Assen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Rode Kruis Ziekenhuis
City
Beverwijk
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Amphia Ziekenhuis
City
Breda
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Haaglanden Medisch Centrum
City
Den Haag
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
HagaZiekenhuis
City
Den Haag
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Nij Smellinghe Ziekenhuis
City
Drachten
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Ziekenhuis Gelderse Vallei
City
Ede
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Admiraal de Ruyter Ziekenhuis
City
Goes
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Groene Hart Ziekenhuis
City
Gouda
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Martini Ziekenhuis
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Radboud University Medical Center
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Ikazia Ziekenhuis
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Diakonessenhuis
City
Utrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Isala Klinieken
City
Zwolle
Country
Netherlands
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.

Learn more about this trial

Leiden Thrombosis Recurrence Risk Prevention

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