Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer (PROVE)

Study Overview
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Brief Summary
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Prospective randomized open multicenter trial with blinded adjudication of endpoints to assess the efficacy of six-month low-dose LMWH (Low Molecular Weight Heparin) for the prevention of symptomatic or incidental VTE in patients with stage IV lung cancer and elevated D-dimer.

Detailed Description
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Adult patients aged ≥ 18 years with stage IV lung cancer and elevated D-dimer will be randomized to the experimental or control group.Patients in the control group will receive usual care, patients in the experimental group will receive subcutaneous tinzaparin once daily for six months. Follow-up visit will take place in outpatient clinic at day 90, day 180 and day 360. Blood sampling for biomarkers will be performed at inclusion visit and day 90.

Official Title
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Long-term Prophylaxis of Venous Thromboembolism With Low-molecular-weight Heparin in Patients With Metastatic Lung Cancer

Conditions
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Venous Thromboembolism, Lung Neoplasm

Intervention / Treatment
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* Drug: Tinzaparin Sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Social security affiliation Written informed consent Histologically confirmed stage IV (M1a or M1b) non-small-cell lung cancer, including recurrent non-small-cell lung cancer after a period of complete remission D-dimer > 1,500 µg/L First line of systemic cancer treatment (chemotherapy, immunotherapy or targeted therapy), or new line of systemic cancer treatment for cancer progression (chemotherapy, immunotherapy or targeted therapy), introduced during the month preceding inclusion or planned within one month after inclusion ECOG (Eastern Cooperative Oncology Group) score 0-2 Life expectancy >3 months Exclusion Criteria: Hypersensitivity to heparin or to any excipients Septic endocarditis History of heparin-induced thrombocytopenia Ongoing anticoagulant treatment at therapeutic dosage VTE at inclusion Creatinin clearance <30 mL/min Active bleeding Platelet count < 100 G/L at inclusion Severe hepatic insufficiency Cancer treated exclusively with supportive care Aspirin at daily dosage > 160 mg Pregnancy Patient under tutorship or curatorship

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>usual care, | |
| Experimental: Experimental<br>tinzaparin sodium | Drug: Tinzaparin Sodium<br>* Subcutaneous tinzaparin 4,500 IU once daily for six months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| venous thromboembolic events | All venous thromboembolism (VTE) events during the six-month treatment period including: objectively confirmed symptomatic pulmonary embolism (PE), objectively confirmed symptomatic lower-limb deep vein thrombosis (DVT) (including iliac and caval thrombosis), objectively confirmed symptomatic upper extremity DVT, objectively confirmed incidentally diagnosed PE or proximal DVT death due to PE. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic VTE events | Objectively confirmed symptomatic VTE and death due to PE | 6 months | 
| Venous thromboembolic events | Objectively confirmed symptomatic or incidental VTE during the 12-months study period | 12 months | 
| Major bleedings | Major bleeding according to the ISTH criteria | 6 months | 
| Death | Overall mortality and causes of death | 6 months | 
| Death | Overall mortality and causes of death | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low-molecular-weight Heparin, Tinzaparin