Recombinant human FVIIa for reducing the need for invasive second‐line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial

• DOI: 10.1111/jth.12844
• Publication Date: 2015-01-16T09:17:06Z
• Authors: G. Lavigne‐Lissalde; A.G. Aya; F.J. Mercier; S. Roger‐Christoph; C. Chauleur; E. Morau; A.S. Ducloy‐Bouthors; A. Mignon; M. Raucoules; A. Bongain; F. Boehlen; P. de Moerloose; S. Bouvet; P. Fabbro‐Peray; J.‐C. Gris
• Keywords: Adult; Compassionate Use Trials; 570; Time Factors; FVIIa activated; 610; Factor XIIa; Hysterectomy; Coagulants/administration & dosage/adverse effects/therapeutic use; Severity of Illness Index; Factor VIII/administration & dosage/adverse effects/therapeutic use; Dinoprostone; Drug Administration Schedule; 03 medical and health sciences; 0302 clinical medicine; treatment efficacy; Pregnancy; Risk Factors; info:eu-repo/classification/ddc/616; Venous Thrombosis/chemically induced; Humans; Treatment Failure; hysterectomy; Infusions, Intravenous; ddc:616; Venous Thrombosis; Hemostatic Techniques/adverse effects; Coagulants; Hemostatic Techniques; Postpartum Hemorrhage; [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology; Postpartum Hemorrhage/diagnosis/drug therapy/mortality; Dinoprostone/analogs & derivatives/therapeutic use; 3. Good health; postpartum hemorrhage; treatment outcome; Female; France; Switzerland

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.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.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.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.