Clinical trial NCT06731244: Shared Decision-making Process for Unprovoked vEnous THromboEmbolism Management. (ETHER )
Official title: Prognosis Improvement of Unprovoked vEnous THromboEmbolism With the Use of a Shared Decision-making Process Including a Time-dependent Multicomponent Risk Prediction Scores inteRvention.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Venous Thromboembolism
Keywords: venous thrombosis
pulmonary embolism
Anticoagulant
deep vein thrombosis
stepped-wedge cluster randomized trial
shared-decision making
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
Collaborators: name: European Commission
name: European Clinical Research Infrastructure Network
First posted: 2024-12-12
Enrollment: 2400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: ETHER is a stepped wedge cluster randomized trial
Primary purpose: OTHER

Brief summary: Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is a frequent disease and the third most common cause of cardiovascular death in the world after myocardial infarction and stroke. Anticoagulant therapy drastically reduces the risk of early VTE recurrence and death, but it exposes patients to a substantial risk of bleeding. Hence, determining the optimal duration of anticoagulant treatment for VTE is a major public health issue.

When major transient risk factors for VTE are identified (major surgery, immobilization...), patients generally do not need to extend anticoagulation beyond 3 months, whereas for VTE diagnosed in the context of cancer, therapeutic anticoagulation is required for as long as the cancer is considered "active".

However, in more than 50% of cases, venous thromboembolic disease occurs spontaneously, i.e. without any significant clinically detectable circumstance (known as unprovoked venous thromboembolic disease). In such patients, the risk of recurrence is high (35% recurrence rate at 5 years, with a 10% risk of death per recurrence). Scientific societies therefore recommend continuing anticoagulant treatment "indefinitely" (i.e. without programming a stop date or long-term treatment). However, this practice exposes these patients to an ongoing, non-negligible increase in the risk of bleeding, which could ultimately exceed the risk of recurrence of venous thrombo-embolic disease.

Optimizing anticoagulant therapy beyond the first three to six months of treatment is therefore a crucial and challenging issue, which could improve the long-term prognosis of patients with unprovoked thromboembolic venous disease.

Based on the quantitative and qualitative approaches implemented in MORPHEUS project granted by European Commission (HORIZON-HLTH-2022-TOOL-11-01 call), the investigators have combined predictive personalized medicine, through the use of risk biomarkers, with a patient-centered model of medicine, which, while based on an understanding of the patient's experience, leading to develop Time-Dependent Multicomponent risk prediction scores and socIo-anthropological scales (TDMI) integrated in a shared decision-making process regarding anticoagulant treatment duration in patients with a first episode of unprovoked VTE.

The aim of this study is to demonstrate that this strategy, based on a medical decision-making process shared between patients and physicians and including TDMI, reduces the risk of recurrence of thromboembolic venous disease (fatal or non-fatal), the risk of bleeding and all-cause mortality, and is associated with greater patient satisfaction after a first episode of unprovoked thromboembolic venous disease.


Eligibility criteria: Inclusion Criteria:

* Patient \> or = 18 years,
* Patient with a first episode of symptomatic unprovoked pulmonary embolism (PE) and/or proximal deep vein thrombosis (DVT) treated for 3 to 6 uninterrupted months with full dose anticoagulant therapy,
* Signed informed consent.

Exclusion Criteria:

* Unable or refusal to give informed consent,
* Isolated distal DVT,
* Isolated sub-segmental PE
* Previous unprovoked VTE
* Known CTEPH
* Indication for anticoagulation other than DVT or PE (e.g.; atrial fibrillation, mechanic valves...),
* Interruption of anticoagulation for 14 days or more before the inclusion,
* Active cancer of less than 24 months,
* Current pregnancy,
* Life expectancy \<18 months (e.g.; patients with an end-stage chronic disease)
* Not affiliated to national insurance, social security (only for France)

Primary outcomes:
measure: Hierarchical composite of adjudicated all-cause mortality, adjudicated symptomatic recurrent VTE (fatal or non-fatal PE or proximal DVT), adjudicated major and clinically relevant non-major bleeding, and patient's satisfaction
timeFrame: From inclusion to 18th month follow-up
Secondary outcomes:
measure: Composite of adjudicated all-cause mortality, symptomatic recurrent VTE (fatal or non-fatal PE or proximal DVT) and major and clinically relevant non-major bleeding
timeFrame: At 18-month follow-up after inclusion
measure: Adjudicated all-cause mortality,
timeFrame: At 18 months follow-up after inclusion
measure: Adjudicated symptomatic VTE recurrence
timeFrame: At 18-month follow-up after inclusion
measure: Adjudicated major bleeding or clinically relevant non-major bleeding
timeFrame: At 18-month follow-up after inclusion
measure: Adjudicated fatal recurrent VTE and fatal bleeding
timeFrame: At 18-month follow-up after inclusion
measure: Patient's satisfaction
timeFrame: At 18-month follow-up after inclusion
measure: Quality of life (QoL) assessed using PembQoL questionnaire
timeFrame: At 18 months after inclusion
measure: Quality of life (QoL) assessed using mMRC dyspnea score
timeFrame: At 18 months after inclusion
measure: Quality of life (QoL) assessed using VEINQol questionnaire
timeFrame: At 18 months after inclusion
measure: Quality of life (QoL) assessed using Villalta score
timeFrame: At 18 months after inclusion
measure: Quality of life (QoL) assessed using EQ-5D5L questionnaire
timeFrame: At 18 months after inclusion
measure: Quality of life (QoL) assessed using PVFS scale patients
timeFrame: At 18 months after inclusion
measure: Therapeutic adherence to anticoagulant treatment
timeFrame: At18-month follow-up after inclusion
measure: Occurence of objectively diagnosed cancer: site, localized, locally advanced, metastatic
timeFrame: From inclusion to 18th months follow-up
measure: Occurence of minor or atypical venous thrombosis
timeFrame: At 18-month follow-up after inclusion
measure: Adjudicated objectively diagnosed acute arterial thromboembolic events according to international guidelines: stroke, myocardial infarction, peripheral arterial thromboembolic event, atrial fibrillation, any cardiac event other than VTE
timeFrame: At 18-month follow-up after inclusion
measure: Adjudicated objectively confirmed chronic thromboembolic pulmonary disease and chronic thromboembolic pulmonary hypertension
timeFrame: At 18-month follow-up after inclusion
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens - Picardie
city: Angers
country: France
facility: CHU d'Angers
city: Brest
country: France
facility: CHU Brest
city: Clamart
country: France
facility: Hôpital National d'Instruction des Armées Percy
city: Clermont Ferrand
country: France
facility: CHU de Clermont Ferrand
city: Colombes
country: France
facility: APHP-Colombes
city: Dijon
country: France
facility: CHU de Dijon - Hôpital François Mitterand
city: Le Mans
country: France
facility: CH Le Mans
city: Lyon
country: France
facility: HCL - Hôpital Edouard Herriot
city: Marseille
country: France
facility: APHM - Hôpital la Timone
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHU de Nancy
city: Nantes
country: France
facility: CHU de Nantes
city: Nîmes
country: France
facility: CHU de Nîmes
city: Paris
country: France
facility: Aphp-Hegp
city: Paris
country: France
facility: Aphp-Hegp
city: Rennes
country: France
facility: CHU de Rennes
city: Saint Etienne
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
References: