Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer (PROVE)

Phase 3

Terminated

• Conditions: Venous Thromboembolism; Lung Neoplasm
• Interventions: Drug: Tinzaparin Sodium

• Registration Number: NCT03090880
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-03-21
• Study First Submitted QC: 2017-03-21
• Study First Posted: 2017-03-27
• Study Start: 2018-09-14
• Primary Completion: 2021-08-18
• Study Completion: 2021-08-18
• Status Verified: 2021-12
• Last Update Submitted: 2022-11-14
• Last Update Posted: 2022-11-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 59

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental	Tinzaparin Sodium	tinzaparin sodium

Primary Outcome Measures

Name	Time	Method
venous thromboembolic events	6 months	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.

Secondary Outcome Measures

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

Trial Locations

Locations (27)

Hôpital Pontchaillou; 🇫🇷 Rennes, Bretagne, France

Centre Hospitalier régional d'Orléans; 🇫🇷 Orléans, Centre, France

Centre Oscar Lambret; 🇫🇷 Lille, Hauts De France, France

Hôpital d'Instruction des Armées Percy; 🇫🇷 Clamart, Ile De France, France

Hôpital Avicenne, Hôpitaux universitaires Paris Seine-; 🇫🇷 Bobigny, Ile De France, France

Hôpital Louis Mourier; 🇫🇷 Colombes, Ile De France, France

Centre Hospitalier de Versailles André Mignot; 🇫🇷 Le Chesnay, Ile De France, France

Centre Hospitalier Intercommunal de Créteil; 🇫🇷 Créteil, Ile De France, France

Hôpital Bicêtre; 🇫🇷 Le Kremlin Bicêtre, Ile De France, France

Hôpital Pitié Salpétrière; 🇫🇷 Paris, Ile De France, France

Centre Hospitalier Paris Saint-Joseph; 🇫🇷 Paris, Ile De France, France

Institut Mutualiste Montsouris; 🇫🇷 Paris, Ile De France, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, Ile De France, France

Hôpital Bichat Claude Bernard; 🇫🇷 Paris, Ile De France, France

Hôpital Tenon; 🇫🇷 Paris, Ile De France, France

Hôpital Foch; 🇫🇷 Suresnes, Ile De France, France

Gustave Roussy; 🇫🇷 Villejuif, Ile De France, France

Hôpital Larrey; 🇫🇷 Toulouse, Languedoc-Roussillon-Midi-Pyrénées, France

Institut de cancérologie de l'Ouest; 🇫🇷 Saint Herblain, Pays De La Loire, France

Centre Hospitalier Annecy Genevois; 🇫🇷 Annecy, Rhône Alpes, France

Groupement Hospitalier Est Hospices civils de Lyon; 🇫🇷 Lyon, Rhônes Alpes, France

CHU de Rouen, Hôpital Charles Nicolle; 🇫🇷 Rouen, Seine Maritime, France

Institut de Cancérologie Lucien Neuwirth; 🇫🇷 Saint Priest, Rhônes-Alpes, France

Institut Curie; 🇫🇷 Paris, Ile De France, France

Centre cardiologique du Nord; 🇫🇷 Saint Denis, Ile De France, France

CHU de Caen; 🇫🇷 Caen, Normandie, France

CHU Poitiers; 🇫🇷 Poitiers, Nouvelle-Aquitaine, France