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rhuFVIIa in Post-partum Hemorrhage

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00370877
Recruitment Status : Completed
First Posted : September 1, 2006
Last Update Posted : March 27, 2015
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

Brief Summary:
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 or disease Intervention/treatment Phase
Postpartum Hemorrhage Drug: rFVIIa Procedure: Standard Care Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Recombinant Human Activated Factor VII as Salvage Therapy in Women With Severe Postpartum Hemorrhage
Study Start Date : April 2007
Actual Primary Completion Date : November 2010
Actual Study Completion Date : November 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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
  • eptacog alpha (activated)

Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Biological parameters:packed red cell volume, hemoglobin, etc. [ Time Frame: 12 hours ]
  4. Therapeutic interventions aiming at controlling postpartum hemorrhage: selective arterial embolization, ligation of hypogastric arteries, hysterectomy. [ Time Frame: Day 1 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00370877

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Hôpital Antoine Béclère -APHP
Clamart, France
University Hospital, Lille
Lille, France
University Hospital of Montpellier
Montpellier, France
University Hospital, Nice
Nice, France
Laboratoire d'hématologie, Groupe Hospitalo-Universitaire Caremeau
Nimes cedex 9, France, F-30029
Centre Hospital University of Nimes
Nimes, France
Maternite CHU de Cochin - APHP
Paris, France
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
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Study Director: Jean-Christophe Gris, MD, PhD University Hospital, Nimes, France

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Centre Hospitalier Universitaire de Nīmes Identifier: NCT00370877     History of Changes
Other Study ID Numbers: PHRC-I/2005/GL-01
2005-005801-40 ( EudraCT Number )
First Posted: September 1, 2006    Key Record Dates
Last Update Posted: March 27, 2015
Last Verified: March 2015

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

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