DVT Burden and the Risk of Post-thrombotic Syndrome (DVT-Burden)

• ClinicalTrials.gov Identifier: NCT06385353
• Recruitment Status: Not yet recruiting
• First Posted: April 26, 2024
• Last Update Posted: April 26, 2024
• Sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Collaborators: Assistance Publique Hopitaux De Marseille; F-CRIN INNOVTE Research Network
• Information provided by (Responsible Party): Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

Tracking Information

• First Submitted Date: April 16, 2024
• First Posted Date: April 26, 2024
• Last Update Posted Date: April 26, 2024
• Estimated Study Start Date: June 2024
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2024)

• Presence of moderate to severe Post-thrombotic Syndrome (PTS) [ Time Frame: 6 months ]
  The primary outcome measure is the presence of moderate or severe PTS at 6 months as determined by a Villalta score ≥ 10 or the presence of an ulcer. The Villalta score considers items based on symptoms and clinical signs, including skin complications, each assessed on a scale from 0 to 3. The Villalta score is used to diagnose PTS and categorise its severity, according to international recommendations. Thrombosis burden is assessed using the VVI index as well as prognostic factors at baseline.
• Thrombosis burden [ Time Frame: Baseline ]
  Thrombosis burden is assessed using the Venous Volumetric Index (VVI) as well as prognostic factors at baseline.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 22, 2024)

• Presence of moderate to severe PTS adjusted to other prognostic factors at baseline [ Time Frame: 6 months ]
  PTS is assessed at 6 months by the Villalta scale.
• Thrombosis burden adjusted to other prognostic factors at baseline [ Time Frame: Baseline ]
  Thrombosis burden is assessed using the VVI index as well as prognostic factors at baseline.
• Presence of moderate to severe PTS adjusted to other prognostic factors at baseline and during follow-up [ Time Frame: Baseline, 1 week, 1 month, 3 months and 6 months ]
  PTS is assessed at 6 months by the Villalta scale. Other prognostic factors related to anticoagulant therapy and compression are assessed during follow-up.
• Thrombosis burden adjusted to other prognostic factors at baseline and during follow-up [ Time Frame: Baseline, 1 week, 1 month, 3 months and 6 months ]
  Thrombosis burden is assessed using the VVI index as well as prognostic factors at baseline. Other prognostic factors related to anticoagulant therapy and compression are assessed during follow-up.
• Time to complete resolution of the thrombus as a function of thrombosis burden at baseline [ Time Frame: up to 6 months ]
• Presence of moderate to severe PTS at baseline and at follow-up visits [ Time Frame: Baseline, 1 week, 1 month, 3 months and 6 months ]
  PTS is assessed by the Villalta scale.
• Thrombosis burden at baseline and at follow-up visits [ Time Frame: Baseline, 1 week, 1 month, 3 months and 6 months ]
  The thrombus burden is assessed by the VVI index.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 22, 2024)

• Disease specific health related quality of life [ Time Frame: 3 months and 6 months ]
  Disease specific health related quality of life will be assessed by the Venous Insufficiency Epidemiological and Economic Study quality of life and symptom (VEINES-QOL/Sym) questionnaires.
• General health related quality of life [ Time Frame: 3 months and 6 months ]
  General health related quality of life will be assessed by the 36-Item Short Form health questionnaire (SF-36). A high score corresponds to better health/quality of life.
• Coagulation and fibrinolysis markers [ Time Frame: up to 3 months ]
  D-dimers, plasminogen activator inhibitor 1 (PAI-1)
• Fibrinolytic and pro-coagulant activities of microvesicles/microparticles [ Time Frame: up to 3 months ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: DVT Burden and the Risk of Post-thrombotic Syndrome
• Official Title: Baseline Ultrasound Venous Thrombosis Burden and the Risk of Post-thrombotic Syndrome in Patients With a First Acute Unprovoked Episode of Symptomatic Deep Vein Thrombosis of the Lower Limbs - The "DVT-Burden" Project -

Brief Summary

Post-thrombotic syndrome (PTS) is the most common chronic complication of deep vein thrombosis (DVT), with major consequences for patient quality of life and cost of management. Identifying patients at high risk of developing PTS could be useful for its prevention and may lead to more appropriate therapeutic strategies to reduce its incidence and severity.

Prognostic tools for predicting risk are very useful for choosing the optimum treatment and improving patient management and are a preliminary step before developing predictive models useful for determining sensitivity to treatment. At present, although several prognostic markers and models have been proposed, it is still difficult to predict who will develop a PTS or a moderate to severe PTS. The development of PTS is multifactorial and depends largely on the extent and severity of venous obstruction which supports the theory of thrombosis burden (DVT-Burden) as a potential prognostic marker for PTS. It therefore seems important to study the association between thrombosis burden and the occurrence of PTS.

The Venous Volumetric Index or VVI (Ouriel 1999) will be used for quantifying DVT-Burden. The VVI was constructed by calculating the volume from the diameter and length of 14 venous segments from the calf veins to the inferior vena cava. The VVI has been validated for its ability to discriminate between symptomatic and asymptomatic DVT and has shown superior performance to other methods for quantifying DVT.

This study aim to assess the performance of baseline DVT-burden estimated by the VVI score on ultrasound for predicting the occurrence and the severity of PTS as assessed by the Villalta scale at 6 months.

Detailed Description

This is a multicenter prospective cohort study aiming at assessing baseline DVT-Burden and other prognostic factors for predicting the occurrence and the severity of PTS.

Patients diagnosed with a first episode of unprovoked DVT of the lower limbs are recruited in offices and departments of vascular medicine. They will be informed of the study by their physician. If patients agree to take part and meet the eligibility criteria, they will be included consecutively in the study after signing an informed consent form.

The study will include follow-up visits at one week (D7±2), 1 month (D30±5), 3 months (D90±5) and 6 months (D180±5).

At each visit, the following examinations will be carried out:

• Assessment of symptoms and clinical signs to evaluate the Villalta score.
• Venous ultrasound evaluation of the lower limbs by colour Doppler ultrasound (CDUS). Data collected will be useful to calculate the VVI score planned at the study analysis phase.

At the D0, D7, D30 and D90 visits, blood samples will be taken for research purposes to assess factors of inflammation, coagulation and fibrinolysis.

At the D90 and D180 visits, the patient will also be asked to complete the VEINES-QOL and SF-36 quality of life questionnaires.

The patient's participation in the research will end at the end of the D180 visit.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Postthrombotic Syndrome

Intervention

Other: Quantification of deep vein thrombosis burden and assessment of post-thrombotic syndrome

Post-thrombotic syndrome will be assessed by the Villalta score until 6 months of follow-up.

Data collected from colour doppler ultrasound will be used to calculate the Venous Volumetric Index to quantify deep vein thrombosis burden until 6 months of follow-up.

Study Arms

Experimental: Association between thrombosis burden and occurrence of PTS

Intervention: Other: Quantification of deep vein thrombosis burden and assessment of post-thrombotic syndrome

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 22, 2024): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Outpatients with acute deep venous thrombosis of the lower limbs confirmed by ultrasound on the criteria of venous incompressibility and direct image of the thrombus
3. Affiliates or beneficiaries of a social security scheme.

Exclusion Criteria:

1. Pregnant women, women in labour or breastfeeding mothers.
2. Suspected or confirmed pulmonary embolism.
3. Asymptomatic venous thrombosis.
4. Bilateral venous thrombosis.
5. History of ipsilateral or contralateral venous thrombosis of the lower limb.
6. DVT caused by a major transient risk factor (surgery with general anaesthetic > 30 minutes in the last 3 months; fracture of the lower limbs in the last 3 months; immobilisation > 3 days for acute medical reasons in the last 3 months; oestroprogestogenic contraception, pregnancy, post-partum, menopausal hormone treatment).
7. DVT caused by a minor risk factor (Surgery with general anaesthetic < 30 minutes in the last 2 months; Trauma to a non-plastered lower limb with reduced mobility ≥ 3 days; Immobilisation < 3 days for acute medical reason in the last 2 months; Travel > 6 hours in the last 2 months).
8. Active cancer defined as cancer for which treatment is ongoing, treatment has not been effective (recurrence or progression) or treatment is palliative.
9. Chronic inflammatory bowel disease.
10. Time between onset of symptoms and diagnosis > 14 days.
11. Prophylactic or therapeutic anticoagulant treatment > 48 hours.
12. Expected duration of anticoagulant treatment < 3 months (all patients must have a minimum treatment of 3 months).
13. Known contraindication to anticoagulant treatment (chronic renal insufficiency defined by creatinine clearance < 30 ml/min according to the Cockcroft-Gault formula; platelets < 100,000/mm3; active bleeding or high risk of bleeding (gastric ulcer, recent haemorrhagic stroke, etc.); known liver disease (Child Pugh class B and class C)).
14. Treatment with antiplatelet agents other than Aspirin ≤ 160 mg/ 24H or Clopidogrel ≤ 75 mg, non-steroidal anti-inflammatory drugs.
15. Indication for interruption of the inferior vena cava or venous recanalisation (endovascular, thrombolysis or surgery).
16. Refusal or inability to give written informed consent to participate in the study.
17. Life expectancy < 6 months.
18. Patients under legal protection (guardianship, curatorship, etc.) or safeguard of justice.
19. Patients taking part in a therapeutic trial for venous thromboembolism.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Magali CESANA; 0483772060; magali.cesana@ch-toulon.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT06385353
• Other Study ID Numbers: 2022-CHITS-003; 2023-A02652-43 ( Other Identifier: ID-RCB number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Original Responsible Party: Same as current
• Current Study Sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Original Study Sponsor: Same as current

Collaborators

• Assistance Publique Hopitaux De Marseille
• F-CRIN INNOVTE Research Network

Investigators

• Study Director: Antoine ELIAS; Centre Hospitalier Intercommunal Toulon La Seyne-sur-Mer

• PRS Account: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Verification Date: April 2024