Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer (PROVE) (PROVE)
Primary Purpose
Venous Thromboembolism, Lung Neoplasm
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Tinzaparin Sodium
Sponsored by
About this trial
This is an interventional prevention trial for Venous Thromboembolism focused on measuring Low-molecular-weight Heparin, Tinzaparin
Eligibility Criteria
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
Sites / Locations
- Hôpital Pontchaillou
- Centre Hospitalier régional d'Orléans
- Centre Oscar Lambret
- Hôpital Avicenne, Hôpitaux universitaires Paris Seine-
- Hôpital d'Instruction des Armées Percy
- Hôpital Louis Mourier
- Centre Hospitalier Intercommunal de Créteil
- Centre Hospitalier de Versailles André Mignot
- Hôpital Bicêtre
- Institut Curie
- Hôpital Pitié Salpétrière
- Centre Hospitalier Paris Saint-Joseph
- Institut Mutualiste Montsouris
- Hôpital Européen Georges Pompidou
- Hôpital Bichat Claude Bernard
- Hôpital Tenon
- Centre cardiologique du Nord
- Hôpital Foch
- Gustave Roussy
- Hôpital Larrey
- CHU de Caen
- CHU Poitiers
- Institut de cancérologie de l'Ouest
- Centre Hospitalier Annecy Genevois
- Groupement Hospitalier Est Hospices civils de Lyon
- Institut de Cancérologie Lucien Neuwirth
- CHU de Rouen, Hôpital Charles Nicolle
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control
Experimental
Arm Description
usual care,
tinzaparin sodium
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Symptomatic VTE events
Objectively confirmed symptomatic VTE and death due to PE
Venous thromboembolic events
Objectively confirmed symptomatic or incidental VTE during the 12-months study period
Major bleedings
Major bleeding according to the ISTH criteria
Death
Overall mortality and causes of death
Death
Overall mortality and causes of death
Full Information
NCT ID
NCT03090880
First Posted
March 21, 2017
Last Updated
November 14, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France, National Cancer Institute, France
1. Study Identification
Unique Protocol Identification Number
NCT03090880
Brief Title
Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer (PROVE)
Acronym
PROVE
Official Title
Long-term Prophylaxis of Venous Thromboembolism With Low-molecular-weight Heparin in Patients With Metastatic Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
The rate of inclusion is too low to hope to reach the target of 800 patients. 59 patients were included, and their data will not meet the research objectives.
The sponsor has decided to prematurely stop inclusions on January 13, 2022.
Study Start Date
September 14, 2018 (Actual)
Primary Completion Date
August 18, 2021 (Actual)
Study Completion Date
August 18, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France, National Cancer Institute, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism, Lung Neoplasm
Keywords
Low-molecular-weight Heparin, Tinzaparin
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
No Intervention
Arm Description
usual care,
Arm Title
Experimental
Arm Type
Experimental
Arm Description
tinzaparin sodium
Intervention Type
Drug
Intervention Name(s)
Tinzaparin Sodium
Intervention Description
Subcutaneous tinzaparin 4,500 IU once daily for six months.
Primary Outcome Measure Information:
Title
venous thromboembolic events
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Symptomatic VTE events
Description
Objectively confirmed symptomatic VTE and death due to PE
Time Frame
6 months
Title
Venous thromboembolic events
Description
Objectively confirmed symptomatic or incidental VTE during the 12-months study period
Time Frame
12 months
Title
Major bleedings
Description
Major bleeding according to the ISTH criteria
Time Frame
6 months
Title
Death
Description
Overall mortality and causes of death
Time Frame
6 months
Title
Death
Description
Overall mortality and causes of death
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Risk factors for venous thromboembolism
Description
Risk factors for venous thromboembolism
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guy Meyer, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Pontchaillou
City
Rennes
State/Province
Bretagne
ZIP/Postal Code
35033
Country
France
Facility Name
Centre Hospitalier régional d'Orléans
City
Orléans
State/Province
Centre
ZIP/Postal Code
45000
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
State/Province
Hauts De France
ZIP/Postal Code
59020
Country
France
Facility Name
Hôpital Avicenne, Hôpitaux universitaires Paris Seine-
City
Bobigny
State/Province
Ile De France
ZIP/Postal Code
93000
Country
France
Facility Name
Hôpital d'Instruction des Armées Percy
City
Clamart
State/Province
Ile De France
ZIP/Postal Code
92140
Country
France
Facility Name
Hôpital Louis Mourier
City
Colombes
State/Province
Ile De France
ZIP/Postal Code
92700
Country
France
Facility Name
Centre Hospitalier Intercommunal de Créteil
City
Créteil
State/Province
Ile De France
ZIP/Postal Code
94000
Country
France
Facility Name
Centre Hospitalier de Versailles André Mignot
City
Le Chesnay
State/Province
Ile De France
ZIP/Postal Code
78157
Country
France
Facility Name
Hôpital Bicêtre
City
Le Kremlin Bicêtre
State/Province
Ile De France
ZIP/Postal Code
94275
Country
France
Facility Name
Institut Curie
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75005
Country
France
Facility Name
Hôpital Pitié Salpétrière
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75013
Country
France
Facility Name
Centre Hospitalier Paris Saint-Joseph
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75014
Country
France
Facility Name
Institut Mutualiste Montsouris
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75014
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75015
Country
France
Facility Name
Hôpital Bichat Claude Bernard
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75018
Country
France
Facility Name
Hôpital Tenon
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75020
Country
France
Facility Name
Centre cardiologique du Nord
City
Saint Denis
State/Province
Ile De France
ZIP/Postal Code
93200
Country
France
Facility Name
Hôpital Foch
City
Suresnes
State/Province
Ile De France
ZIP/Postal Code
92150
Country
France
Facility Name
Gustave Roussy
City
Villejuif
State/Province
Ile De France
ZIP/Postal Code
94805
Country
France
Facility Name
Hôpital Larrey
City
Toulouse
State/Province
Languedoc-Roussillon-Midi-Pyrénées
ZIP/Postal Code
31059
Country
France
Facility Name
CHU de Caen
City
Caen
State/Province
Normandie
ZIP/Postal Code
14033
Country
France
Facility Name
CHU Poitiers
City
Poitiers
State/Province
Nouvelle-Aquitaine
ZIP/Postal Code
86000
Country
France
Facility Name
Institut de cancérologie de l'Ouest
City
Saint Herblain
State/Province
Pays De La Loire
ZIP/Postal Code
44805
Country
France
Facility Name
Centre Hospitalier Annecy Genevois
City
Annecy
State/Province
Rhône Alpes
ZIP/Postal Code
74374
Country
France
Facility Name
Groupement Hospitalier Est Hospices civils de Lyon
City
Lyon
State/Province
Rhônes Alpes
ZIP/Postal Code
69000
Country
France
Facility Name
Institut de Cancérologie Lucien Neuwirth
City
Saint Priest
State/Province
Rhônes-Alpes
ZIP/Postal Code
42270
Country
France
Facility Name
CHU de Rouen, Hôpital Charles Nicolle
City
Rouen
State/Province
Seine Maritime
ZIP/Postal Code
76000
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer (PROVE)
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