DVT Burden and the Risk of Post-thrombotic Syndrome

Postthrombotic Syndrome Clinical Trial

— DVT-Burden  

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 -

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06385353
• Other study ID #: 2022-CHITS-003
• Secondary ID: 2023-A02652-43
• Status: Recruiting
• Phase: N/A
• Start date: June 5, 2024
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Contact: Magali CESANA
• Phone: 0483772060
• Email: magali.cesana[@]ch-toulon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Postphlebitic Syndrome
• Postthrombotic Syndrome
• Syndrome
• Venous Thrombosis

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.

Locations

Country	Name	City	State
France	Cabinet libéral	Ajaccio	Corse-du-sud
France	Cabinet libéral	Ajaccio	Corse-du-sud
France	Centre Hospitalier Universitaire Amiens Picardie	Amiens	Somme
France	Centre Hospitalier d'Avignon	Avignon	Vaucluse
France	Centre Hospitalier Universitaire de Brest	Brest	Finistère
France	Centre Hospitalier de Carcassonne	Carcassonne	Aude
France	Centre Hospitalier de Fréjus/Saint-Raphaël	Fréjus	Var
France	Hospices Civils de Lyon, Hôpital Edouard Herriot	Lyon	Rhône
France	Cabinet libéral	Martigues	Bouches-du-Rhône
France	Centre Hospitalier Universitaire de Nantes	Nantes
France	Polyclinique Les Fleurs	Ollioules	Var
France	Centre cardio-vasculaire Esterel	Saint-Raphaël	Var
France	Cabinet libéral	Sanary-sur-Mer	Var
France	Cabinet libéral	Six-Fours-les-Plages	Var
France	Centre Hospitalier Intercommunal Toulon La Seyne-sur-Mer	Toulon	Var
France	Clinique Rive Gauche	Toulouse	Haut-Garonne

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer	Assistance Publique Hopitaux De Marseille, F-CRIN INNOVTE Research Network

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Disease specific health related quality of life	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.	3 months and 6 months
Other	General health related quality of life	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.	3 months and 6 months
Other	Coagulation and fibrinolysis markers	D-dimers, plasminogen activator inhibitor 1 (PAI-1)	up to 3 months
Other	Fibrinolytic and pro-coagulant activities of microvesicles/microparticles		up to 3 months
Primary	Presence of moderate to severe Post-thrombotic Syndrome (PTS)	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.	6 months
Primary	Thrombosis burden	Thrombosis burden is assessed using the Venous Volumetric Index (VVI) as well as prognostic factors at baseline.	Baseline
Secondary	Presence of moderate to severe PTS adjusted to other prognostic factors at baseline	PTS is assessed at 6 months by the Villalta scale.	6 months
Secondary	Thrombosis burden adjusted to other prognostic factors at baseline	Thrombosis burden is assessed using the VVI index as well as prognostic factors at baseline.	Baseline
Secondary	Presence of moderate to severe PTS adjusted to other prognostic factors at baseline and during follow-up	PTS is assessed at 6 months by the Villalta scale. Other prognostic factors related to anticoagulant therapy and compression are assessed during follow-up.	Baseline, 1 week, 1 month, 3 months and 6 months
Secondary	Thrombosis burden adjusted to other prognostic factors at baseline and during follow-up	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.	Baseline, 1 week, 1 month, 3 months and 6 months
Secondary	Time to complete resolution of the thrombus as a function of thrombosis burden at baseline		up to 6 months
Secondary	Presence of moderate to severe PTS at baseline and at follow-up visits	PTS is assessed by the Villalta scale.	Baseline, 1 week, 1 month, 3 months and 6 months
Secondary	Thrombosis burden at baseline and at follow-up visits	The thrombus burden is assessed by the VVI index.	Baseline, 1 week, 1 month, 3 months and 6 months