Shared Decision-making Process for Unprovoked vEnous THromboEmbolism Management. (ETHER ) (ETHER)

Prognosis Improvement of Unprovoked vEnous THromboEmbolism With the Use of a Shared Decision-making Process Including a Time-dependent Multicomponent Risk Prediction Scores inteRvention.

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.

Study Overview

• Status: Recruiting
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Other: Usual Care Group; Other: shared decision-making process

• Study Type: Interventional
• Enrollment (Estimated): 2400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Francis COUTURAUD, Prof.; Phone Number: +33298347348; Email: francis.couturaud@chu-brest.fr
• Study Contact Backup: Name: Hélène FORTIN-PRUNIER; Phone Number: +33221744115; Email: helene.fortin-prunier@chu-brest.fr

Study Locations

• France
  • Amiens, France, 80054
    • Not yet recruiting
    • CHU d'Amiens - Picardie
    • Contact: Marie-Antoinette SEVESTRE, Dr.; Phone Number: + 33322087306; Email: sevestre.marie-antoinette@chu-amiens.fr
  • Angers, France, 49933
    • Not yet recruiting
    • CHU d'Angers
    • Contact: Jeanne HERSANT, Dr.; Phone Number: +33241353689; Email: Jeanne.Hersant@chu-angers.fr
  • Clamart, France, 92140
    • Not yet recruiting
    • Hôpital National d'Instruction des Armées Percy
    • Contact: Caroline DOUTRELON, Dr.; Phone Number: +33141466252; Email: caroline.doutrelon@intradef.gouv.fr
  • Clermont-Ferrand, France, 63000
    • Not yet recruiting
    • CHU de Clermont Ferrand
    • Contact: Jeannot SCHMIDT, Prof.; Phone Number: +33473754549; Email: jschmidt@chu-clermontferrand.fr
  • Colombes, France, 92700
    • Not yet recruiting
    • APHP-Colombes
    • Contact: Isabelle MAHE, Prof.; Phone Number: +33147606490; Email: isabelle.mahe@aphp.fr
  • Dijon, France, 21079
    • Not yet recruiting
    • CHU de Dijon - Hôpital François Mitterand
    • Contact: Nicolas FALVO, Dr.; Phone Number: +33380295586; Email: nicolas.falvo@chu-dijon.fr
  • Le Mans, France, 72037
    • Not yet recruiting
    • CH Le Mans
    • Contact: Claire NEVEUX, Dr.; Phone Number: +33243434343; Email: cneveux@ch-lemans.fr
  • Lyon, France, 69003
    • Not yet recruiting
    • Hcl - Hopital Edouard Herriot
    • Contact: Judith CATELLA, Dr.; Phone Number: +33472117791; Email: judith.catella@chu-lyon.fr
  • Marseille, France, 13005
    • Not yet recruiting
    • Aphm - Hopital La Timone
    • Contact: Gabrielle SARLON BARTOLI, Dr.; Phone Number: +33491387023; Email: gabrielle.sarlon@ap-hm.fr
  • Montpellier, France, 34295
    • Not yet recruiting
    • CHU de Montpellier
    • Contact: Isabelle QUERE, Prof.; Phone Number: +33467337025; Email: i-quere@chu-montpellier.fr
  • Nancy, France, 54511
    • Not yet recruiting
    • CHU de NANCY
    • Contact: Stéphane ZUILY, Prof.; Phone Number: +33383153614; Email: s.zuily@chru-nancy.fr
  • Nantes, France, 44093
    • Not yet recruiting
    • CHU de Nantes
    • Contact: Jérôme CONNAULT, Dr.; Phone Number: +33240083848; Email: jerome.connault@chu-nantes.fr
  • Nîmes, France, 30029
    • Not yet recruiting
    • CHU de Nimes
    • Contact: Valérie RAY, Dr.; Phone Number: +33466685131; Email: valerie.ray@chu-nimes.fr
  • Paris, France, 75015
    • Not yet recruiting
    • Aphp-Hegp
    • Contact: Lina Khider, Dr.; Phone Number: +33156093077; Email: lina.khider@aphp.fr
  • Rennes, France, 35200
    • Not yet recruiting
    • CHU de Rennes
    • Contact: Alice BALLERIE, Prof.; Phone Number: +33299284321; Email: alice.ballerie@chu-rennes.fr
  • Saint-Etienne, France, 42270 Saint Priest En Jarez
    • Not yet recruiting
    • CHU Saint Etienne
    • Contact: Laurent BERTOLETTI, Prof.; Phone Number: + 33477127596; Email: laurent.bertoletti@chu-st-etienne.fr
  • Strasbourg, France, 67091
    • Not yet recruiting
    • CHU de Strasbourg
    • Contact: Dominique STEPHAN, Prof.; Phone Number: +33369550952; Email: Dominique.Stephan@chru-strasbourg.fr
  • Toulouse, France, 31000
    • Not yet recruiting
    • CHU de Toulouse
    • Contact: Alessandra BURA-RIVIERE, Prof.; Phone Number: +33561322448; Email: bura-riviere.a@chu-toulouse.fr
  • France
    • Brest, France, France, 29609
      • Recruiting
      • CHU Brest
      • Contact: Francis COUTURAUD, Prof; Phone Number: +33298347348; Email: francis.couturaud@chu-brest.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm; Anticoagulant treatment management according to usual practice and international guidelines	Other: Usual Care Group; Patients will be managed as regards their anticoagulant treatment according to usual practice and in accordance with international guidelines.
Experimental: Experimental arm; Shared decision-making process integrating time-dependent multicomponent risk prediction scores and socio-anthropological scales (TDMI)	Other: shared decision-making process; The intervention is based on a strategy based on a shared decision-making process which is a collaborative process that involves a patient and their healthcare professional working together to reach a joint decision about care (anticoagulant treatment). The shared decision-making process will be conducted as follows: Step 1: prepare the risk estimates (risk of recurrent VTE, risk of bleeding) for the patient, based on time-dependent multicomponent risk prediction scores and socio-anthropological scales (TDMI) and other validated risk prediction scores and evidence-based medicine;; Step 2: Communicating risks, benefits and consequences to the patient;; Step 3: Make a joint decision about treatment and care, and agree together when this will be reviewed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	For the statistical analysis, the investigators will analyse hierarchically each component of the composite (all-cause mortality, then VTE recurrence, then major bleeding or clinically relevant non-major bleeding and then patient's satisfaction in this order) using a win ratio approach to assess the primary composite outcome.	From inclusion to 18th month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	This clinical composite outcome will be compared between the intervention group and the control group at the individual level with a mixed effect cox model with a random intercept to account for the correlation between patients of a same cluster. The random intercept will correspond to a random period effect nested in a random cluster effect. Different covariance structure will be tested, the model will be selected as the best identifiable model that produces the lowest Bayesian Information Criterion (BIC) value. The effect of the intervention (shared decision-making process including a TDMI) will be then presented as the hazard ratio between the two groups of treatment and its corresponding 95% CI. A random cluster effect will be added to the treatment group effect, if necessary, to quantify any heterogeneity in the benefit of the intervention. The superiority test on this outcome will be performed only if the primary outcome is statistically demonstrated.	At 18-month follow-up after inclusion
Adjudicated all-cause mortality,		At 18 months follow-up after inclusion
Adjudicated symptomatic VTE recurrence		At 18-month follow-up after inclusion
Adjudicated major bleeding or clinically relevant non-major bleeding		At 18-month follow-up after inclusion
Adjudicated fatal recurrent VTE and fatal bleeding		At 18-month follow-up after inclusion
Patient's satisfaction	Patient's satisfaction will be defined with the Patient Activation Measure - PAM score using 13 items measures that assess patient's knowledge, skill, and confidence for self-management. The scoring (for each criteria) is: Strongly disagree = 1; Disagree = 2; Agree = 3; Strongly agree = 4	At 18-month follow-up after inclusion
Quality of life (QoL) assessed using PembQoL questionnaire	Evaluation only for patients with symptomatic PE. The PEmb-QoL Score is ranged between 0% and 100% for each of its 6 dimensions. Higher scores indicate worse outcome.	At 18 months after inclusion
Quality of life (QoL) assessed using mMRC dyspnea score	Evaluation only for patients with symptomatic PE. Scale ranged from 0 (no dyspnea) to 5 (worst grade)	At 18 months after inclusion
Quality of life (QoL) assessed using VEINQol questionnaire	Evaluation only for patients with symptomatic DVT. Responses are rated on two-point to seven-point Likert response scales of intensity, frequency, or agreement.	At 18 months after inclusion
Quality of life (QoL) assessed using Villalta score	Evaluation only for patients with symptomatic DVT. The total Villalta score, ranging from 0 to 33, will be assessed in both legs and used to categorize the severity of PTS in the index leg as mild (score, 5-9), moderate (score, 10-14), or severe (score, ≥15 or presence of ulceration).	At 18 months after inclusion
Quality of life (QoL) assessed using EQ-5D5L questionnaire	Five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels. The patient is asked to indicate his/her health state.	At 18 months after inclusion
Quality of life (QoL) assessed using PVFS scale patients	Scale ranged from 0 (normal functional status) to 5 (worse grade)	At 18 months after inclusion
Therapeutic adherence to anticoagulant treatment	Therapeutic adherence using Girerd's questionnaire: 6 items. Score 0 = good compljance ; Score 1-2 = minor concern in compliance ; Score ≥ 3 = bad compliance.	At18-month follow-up after inclusion
Occurence of objectively diagnosed cancer: site, localized, locally advanced, metastatic	Cancers will be classified according the site and the extend (localized, locally advanced, metastatic).	From inclusion to 18th months follow-up
Occurence of minor or atypical venous thrombosis	Minor venous thrombosis includes superficial vein thrombosis, muscular and distal deep vein thrombosis. Atypical venous thrombosis includes: Proximal upper limbs Superior vena cava, Cerebral venous thrombosis, Portal thrombosis, Mesenteric thrombosis, Sus-hepatic vein thrombosis, Renal thrombosis, Ovarian vein thrombosis, Uterine vein thrombosis, Retinal vein thrombosis.	At 18-month follow-up after inclusion
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		At 18-month follow-up after inclusion
Adjudicated objectively confirmed chronic thromboembolic pulmonary disease and chronic thromboembolic pulmonary hypertension		At 18-month follow-up after inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Collaborators: European Commission; European Clinical Research Infrastructure Network

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2025
• Primary Completion (Estimated): October 1, 2035
• Study Completion (Estimated): October 1, 2035

Study Registration Dates

• First Submitted: November 8, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: shared-decision making; venous thrombosis; deep vein thrombosis; pulmonary embolism; Anticoagulant; stepped-wedge cluster randomized trial
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Thrombosis; Pulmonary Embolism; Venous Thrombosis; Venous Thromboembolism
• Other Study ID Numbers: 29BRC23.0189; 2024-A01652-45 (Other Identifier: IDRCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No