rhuFVIIa in Post-partum Hemorrhage

This study has been completed.
Sponsor:
Collaborators:
University Hospital, Lille
Assistance Publique - Hôpitaux de Paris
University Hospital, Montpellier
University Hospital, Geneva
Centre Hospitalier Universitaire de Nice
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier:
NCT00370877
First received: August 30, 2006
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

The aim of this clinical research project is to evaluate the use of the recombinant human activated factor VII (rhFVIIa), given as a salvage therapy, in women with a dramatic postpartum hemorrhage still ongoing after all the currently available medical and surgical treatments. We are going to compare its early use, before elective surgery or arterial embolization, to its late use, after embolization or surgery, before salvage hysterectomy.


Condition Intervention Phase
Postpartum Hemorrhage
Drug: rFVIIa
Procedure: Standard Care
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Recombinant Human Activated Factor VII as Salvage Therapy in Women With Severe Postpartum Hemorrhage

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nīmes:

Primary Outcome Measures:
  • Clinical parameters: intensity of the hemorrhage, before and one hour after the end of the rhuFVIIa infusion (use of a graduated blood collector bag device). [ Time Frame: 1 hour ] [ Designated as safety issue: Yes ]
  • Any transfusion (number of units and volume) of red blood cells, platelet or fresh frozen plasma. Haemodynamics-related parameters (non-invasive arterial pressure,heart rate, diuresis,..). [ Time Frame: 7 Hours ] [ Designated as safety issue: Yes ]
  • Biological parameters:packed red cell volume, hemoglobin, etc. [ Time Frame: 12 hours ] [ Designated as safety issue: Yes ]
  • Therapeutic interventions aiming at controlling postpartum hemorrhage: selective arterial embolization, ligation of hypogastric arteries, hysterectomy. [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]

Enrollment: 84
Study Start Date: February 2007
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard care for post-partum hemorrhage
The patients included in this arm of the study will recieve standard care for post-partum hemorrhage.
Procedure: Standard Care
Patients will recieve standard care for post partum hemorrhage according to current recommendations.
Other Name: Standard
Experimental: rFVIIa
The patients included in this arm of the study will recieve standard care for post-partum hemorrhage plus a slow intravenous injection (2ml/min) of rFVIIa (60µg/kg)
Drug: rFVIIa
The patients included in this arm of the study will recieve standard care for post-partum hemorrhage plus a slow intravenous injection (2ml/min) of rFVIIa (60µg/kg)
Other Names:
  • Experimental
  • Novo 7
  • rFVIIa
  • eptacog alpha (activated)

Detailed Description:

Depending on the country and the publications, postpartum hemorrhage is either the first or the second cause of maternal death in the world, including developed countries. According to the WHO, it is responsible for twenty two percent of maternal deaths. In France, postpartum hemorrhage accounts for five percent of delivery complications. Three percent of them are severe, leading to uncontrolled bleeding which intensity is higher than 1000 ml of blood during the 24 hours following delivery. In France, they are involved in 20 new deaths per year; it is the first cause of maternal mortality. Indeed, it remains a significant source of morbidity: severe anaemia, blood transfusion, transfusion complications, acquired coagulation disorders and hemostatic hysterectomy.

There are two different types of postpartum hemorrhage: early and late hemorrhages. Early hemorrhages are more common and occur in the first 24H after delivery. Uterine atony is the main cause of early hemorrhage. However, visual assessment underestimates the amount of blood loss in around forty five percent of cases. Emergency treatment is therefore sometimes undertaken with some delay, giving time for disseminated intravascular coagulation (DIC) to occur, which worsens the prognosis. They are usually treated by medical resuscitation, blood transfusion, selective arterial embolisation and finally hysterectomy in case of ongoing uncontrolled bleeding. Medical treatment and obstetric manoeuvres are usually effective. Artificial delivery of the placenta should be performed immediately if the placenta is incomplete. Afterwards, oxytocin and prostaglandin derivatives are given. At the same time, anemia and hemostatic abnormalities are treated by transfusion of fresh frozen plasma and packed cells. When the measures are insufficient, surgery is necessary. Bilateral ligation of hypogastric arteries or controlled embolisation is recommended. In the case of uncontrolled bleeding, hemostatic hysterectomy is performed as a salvage therapy. Also, the efficacy of ligation of the hypogastric arteries remains controversial. Therefore, the success rate of ligation of the hypogastric arteries is only forty two percent, so that in many cases hysterectomy is required, which induces a definitive sterility. The development of interventional radiology has offered a new approach for the management of postpartum hemorrhage. Many publications have showed the usefulness of the procedure, whose success rate is around ninety percent. However, a specific technical plateau is needed, which is far to be available at any place and at any moment. For patients delivering far away from these technical sites, limiting blood loss is crucial. Among the methods aiming at limiting obstetrical hemorrhage, special concern was given to recombinant activated factor VII, a drug used with good therapeutic results in symptomatic patients with hemophilia and inhibitors. It has already been applied in interventions situations.

Taking into consideration the above described aspects, our goal is thus to evaluate the potential medical interest of giving rhFVIIa early in the course of hemorrhage, compared to giving it as a salvage therapy after arterial selective embolization or hysterectomy in patients still bleeding, in order to avoid hemostatic hysterectomy.

In the literature, IV infusion of rFVIIa stopped ongoing diffuse hemorrhage, rapidly, and no further transfusion was required after rFVIIa injection. Then rFVIIa, might be a strong complementary agent in the management of major postpartum hemorrhage. Optimal dose, timing and safety characteristics of rFVIIa administration remain to be determined.

Therefore, the main objectives of the study are:

  1. to evaluate the reduction of the absolute risk of arterial embolization/surgery/hysterectomy in patients receiving a unique early infusion of rhuFVIIa (60 µg/kg body weight);
  2. to evaluate the number of women necessary to treat to avoid one arterial embolization/surgery/hysterectomy.
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Severe postpartum hemorrhage, i.e non responsive to sulprostone infusion

Exclusion Criteria:

  • < 18 years
  • personal antecedent of arterial or venous thrombosis
  • written informed consent not approved/signed by the patient or her husband
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00370877

Locations
France
Hôpital Antoine Béclère -APHP
Clamart, France
University Hospital, Lille
Lille, France
University Hospital of Montpellier
Montpellier, France
University Hospital, Nice
Nice, France
Centre Hospital University of Nimes
Nimes, France
Laboratoire d'hématologie, Groupe Hospitalo-Universitaire Caremeau
Nimes cedex 9, France, F-30029
Maternite CHU de Cochin - APHP
Paris, France
Switzerland
University Hospital, Geneva
Geneva, Switzerland
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
University Hospital, Lille
Assistance Publique - Hôpitaux de Paris
University Hospital, Montpellier
University Hospital, Geneva
Centre Hospitalier Universitaire de Nice
Investigators
Study Director: Jean-Christophe Gris, MD, PhD University Hospital, Nimes, France
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT00370877     History of Changes
Other Study ID Numbers: PHRC-I/2005/GL-01, 2005-005801-40
Study First Received: August 30, 2006
Last Updated: March 3, 2014
Health Authority: France: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Hospitalier Universitaire de Nīmes:
Post-partum hemorrhage
Arterial embolization
Surgery
Hysterectomy
Activated recombinant human factor VII

Additional relevant MeSH terms:
Hemorrhage
Postpartum Hemorrhage
Pathologic Processes
Obstetric Labor Complications
Pregnancy Complications
Puerperal Disorders
Uterine Hemorrhage

ClinicalTrials.gov processed this record on April 14, 2014