title: Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.
abstract: BACKGROUND
  Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available.
  
  
  METHODS
  Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion.
  
  
  RESULTS
  rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism.
  
  
  CONCLUSIONS
  This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.
authors.affiliation: Laboratory of Hematology, Carémeau University Hospital, Nîmes, France; Research group EA2992, Montpellier University, Nîmes, France.
authors.forename: G
authors.initials: G
authors.lastname: Lavigne-Lissalde
authors.forename: A G
authors.initials: AG
authors.lastname: Aya
authors.forename: F J
authors.initials: FJ
authors.lastname: Mercier
authors.forename: S
authors.initials: S
authors.lastname: Roger-Christoph
authors.forename: C
authors.initials: C
authors.lastname: Chauleur
authors.forename: E
authors.initials: E
authors.lastname: Morau
authors.forename: A S
authors.initials: AS
authors.lastname: Ducloy-Bouthors
authors.forename: A
authors.initials: A
authors.lastname: Mignon
authors.forename: M
authors.initials: M
authors.lastname: Raucoules
authors.forename: A
authors.initials: A
authors.lastname: Bongain
authors.forename: F
authors.initials: F
authors.lastname: Boehlen
authors.forename: P
authors.initials: P
authors.lastname: de Moerloose
authors.forename: S
authors.initials: S
authors.lastname: Bouvet
authors.forename: P
authors.initials: P
authors.lastname: Fabbro-Peray
authors.forename: J-C
authors.initials: JC
authors.lastname: Gris
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D011247:Pregnancy; D003029:Coagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D057176:Compassionate Use Trials; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005602:France; D006489:Hemostatic Techniques / Q000009:adverse effects; D007044:Hysterectomy; D007262:Infusions, Intravenous; D006473:Postpartum Hemorrhage / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D012307:Risk Factors; D012720:Severity of Illness Index; D013557:Switzerland; D013997:Time Factors; D017211:Treatment Failure; D020246:Venous Thrombosis / Q000139:chemically induced; D015956:Factor XIIa
chemical_list: D003029:Coagulants; D015232:Dinoprostone; C016767:sulprostone; D015956:Factor XIIa
keywords: FVIIa activated; hysterectomy; postpartum hemorrhage; treatment efficacy; treatment outcome