rhuFVIIa in Post-partum Hemorrhage
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): rFVIIa; Standard Care
Intervention type(s): Drug; Procedure
Intervention description(s): 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); Patients will recieve standard care for post partum hemorrhage according to current recommendations.
Other intervention name(s): Experimental; Novo 7; eptacog alpha (activated); Standard
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Post-partum hemorrhage; Arterial embolization; Surgery; Hysterectomy; Activated recombinant human factor VII