Clinical trial NCT00457158: PREPIC 2 : Prevention of Recurrent Pulmonary Embolism by Vena Cava Interruption
Official title: PREPIC 2 : Interruption of Inferior Vena Cava by a Retrievable Filter for the Prevention of Recurrent Pulmonary Embolism : a Randomised, Open Label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Embolism
Venous Thrombosis
Keywords: pulmonary embolism
inferior vena cava filters
venous thrombosis
randomized controlled trial
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Fondation de France
name: Fondation de l'Avenir
name: ALN Implants Company
First posted: 2007-04-05
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess efficacy and safety of optional vena cava filter implanted 3 months in prevention of recurrent pulmonary embolism in patients presenting with acute pulmonary embolism associated with thrombotic risk factors

Detailed description: Pulmonary embolism is a common pathology, which could be fatal (about 10 000 death/year in France). It mainly originates from a deep vein thrombosis. In order to reduce mortality, prevention of new or recurrent PE is a major therapeutic aim. Only one randomised trial (PREPIC) assessed the interest of a vena cava filter in patients treated by anticoagulant treatment for a deep vein thrombosis (DVT). Results show a significant 50 % reduction of the embolic risk with the filter. This benefit occurs from the first days, but are counterbalanced by a long-term increasing risk of recurrent DVT. The filter appears promising in patients with a high risk of PE, for exemple the elderly, presenting with a thromboembolic history, cancer, heart failure or respiratory insufficiency, or a recent PE. Moreover, retrievable filters, which may be either left in place permanently or retrieved after some days or weeks, could limit the filter thrombosis risk.

The aim of PREPIC 2 study is to assess, in a multicenter randomised trial, efficacy and safety of a retrievable vena cava filter implanted 3 months versus no filter in 400 patients treated with anticoagulant drugs for a symptomatic PE associated with at least one thrombotic risk factor. A clinical follow-up will be performed at 6 months. The primary outcome is the incidence of recurrent PE at 3 months, including symptomatic and fatal PE. It will be adjudicated by an independent committee, blinded to patients' allocation.

This study will assess the benefit risk ratio of the retrievable filter for the prevention of recurrent PE, without increasing the thrombotic risk and the disadvantage due to post thrombotic syndrome.

Eligibility criteria: Inclusion Criteria:

* Informed consent
* Acute symptomatic pulmonary embolism; AND
* Deep or superficial vein thrombosis; AND
* At least one of the risk factors below :

  * More than 75 years old
  * Evolutiv cancer (excepting locally cutaneous cancer)
  * Known chronic heart failure treated
  * Chronic respiratory insufficiency treated
  * Bilateral deep vein thrombosis
  * Ilio-cava thrombosis
  * Ischemic stroke \> 3 days and \< 6 months, with lower limb deficit
  * Cardiac repercussion of pulmonary embolism assessed by echocardiography or increasing troponin I or T, or Brain Natriuretic Peptid or proBNP

Exclusion Criteria:

* Contrindication to an anticoagulant treatment or recurrent thromboembolic event despite adequate anticoagulation
* Vena cava filter already inserted
* Filter insertion impossible due to caval thrombosis
* More than 72 hours pre-randomized treatment with therapeutic dosage of anticoagulant therapy
* Non carcinologic surgery within 3 months prior randomization
* Carcinologic surgery within 10 days prior randomization
* Hypersensitivity to contrast media
* Access port in place or programmed within 3 months
* Woman who are child bearing
* Life expectancy \< 6 months

Primary outcomes:
measure: at 3 months, combined criteria including recurrent PE confirmed by objective tests and fatal PE confirmed by autopsy and death which can not be attribuated to a documented cause and for which PE/DVT can't be ruled out
timeFrame: 3 months
Secondary outcomes:
measure: recurrent pulmonary embolism, fatal or not, at 6 months (combined criteria including recurrent pulmonary ambolism confirmed by objective tests and fatal PE confirmed by autopsy and death which can not be attribuated to a documented cause and for which P
timeFrame: 6 months
measure: current or new symptomatic DVT confirmed by objective tests
timeFrame: 6 months
measure: mecanical complication of filter (migration, tilt, transfixion) and or puncture site hematoma, and/or local or general infection due to filter
timeFrame: 6 months
measure: filter thrombosis
timeFrame: 6 months
measure: filter retrieval failure
timeFrame: 6 months
measure: total death
timeFrame: 6 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Service de Médecine Vasculaire, CHU Amiens
city: Angers
country: France
facility: Service d'Accueil des Urgences, CHU d'Angers
city: Besançon
country: France
facility: Service de Cardiologie, CHU de Besançon
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Brest
country: France
facility: Département de Medecine Interne et Pneumologie, CHU de Brest
city: Clamart
country: France
facility: Service de Pneumologie, Hôpital Antoine Beclere
city: Clermont Ferrand
country: France
facility: Service d'Accueil des Urgences, CHU de Clermont Ferrand
city: Dijon
country: France
facility: CHU de Dijon
city: Firminy
country: France
facility: Service des Urgences, CHG de Firminy
city: Grenoble
country: France
facility: Unité de Médecine Vasculaire, CHU de Grenoble
city: Lille
country: France
facility: Service d'Urgences Soins Intensifs cardiologiques, CHU de Lille
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Montpellier
country: France
facility: Service de Medecine Interne et Maladies Vasculaires, CHU de Montpellier
city: Nancy
country: France
facility: Service de Medecine Interne et Vasculaire, CHU de Nancy
city: Nice
country: France
facility: Service de Cardiologie, CHU de Nice
city: Paris
country: France
facility: Département de Pneumologie, Hôpital Européen Georges Pompidou, AP HP
city: Saint-Etienne
country: France
facility: Service d'Urgences et de Réanimation Medicale, CHU de Saint-Etienne
city: Saint-Etienne
country: France
facility: Service de Medecine et Therapeutique - CHU de Saint-Etienne
city: Toulon
country: France
facility: Service de Médecine Vasculaire, CH Toulon
city: Tours
country: France
facility: Service de Cardiologie, CHU de Tours
Study officials:
affiliation: CHU de Saint-Etienne
name: Patrick MISMETTI, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral FG, Huet Y, Simonneau G. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prevention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998 Feb 12;338(7):409-15. doi: 10.1056/NEJM199802123380701.
citation: PREPIC Study Group. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study. Circulation. 2005 Jul 19;112(3):416-22. doi: 10.1161/CIRCULATIONAHA.104.512834. Epub 2005 Jul 11.
citation: Mismetti P, Laporte S, Pellerin O, Ennezat PV, Couturaud F, Elias A, Falvo N, Meneveau N, Quere I, Roy PM, Sanchez O, Schmidt J, Seinturier C, Sevestre MA, Beregi JP, Tardy B, Lacroix P, Presles E, Leizorovicz A, Decousus H, Barral FG, Meyer G; PREPIC2 Study Group. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial. JAMA. 2015 Apr 28;313(16):1627-35. doi: 10.1001/jama.2015.3780.