title: Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial.
abstract: BACKGROUND
  Oxytocin, the gold-standard treatment for post-partum haemorrhage, needs refrigeration, intravenous infusion, and skilled providers for optimum use. Misoprostol, a potential alternative, is increasingly used ad hoc for treatment of post-partum haemorrhage; however, evidence is insufficient to lend support to recommendations for its use. This trial established whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum haemorrhage in women receiving prophylactic oxytocin.
  
  
  METHODS
  In this double-blind, non-inferiority trial, 31 055 women exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (two secondary-level and three tertiary-level facilities). 809 (3%) women were diagnosed with post-partum haemorrhage and were randomly assigned to receive 800 mug misoprostol (n=407) or 40 IU intravenous oxytocin (n=402). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350.
  
  
  RESULTS
  All randomly assigned participants were analysed. Active bleeding was controlled within 20 min after initial treatment for 363 (89%) women given misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0.99, 95% CI 0.95-1.04; crude difference 0.4%, 95% CI -3.9 to 4.6). Additional blood loss of 300 mL or greater after treatment occurred for 139 (34%) women receiving misoprostol and 123 (31%) receiving oxytocin (RR 1.12, 95% CI 0.92-1.37). Shivering (152 [37%] vs 59 [15%]; RR 2.54, 95% CI 1.95-3.32) and fever (88 [22%] vs 59 [15%]; 1.47, 1.09-1.99) were significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women died.
  
  
  CONCLUSIONS
  Misoprostol is clinically equivalent to oxytocin when used to stop excessive post-partum bleeding suspected to be due to uterine atony in women who have received oxytocin prophylactically during the third stage of labour.
authors.affiliation: Gynuity Health Projects, New York, NY 10010, USA. jblum@gynuity.org
authors.forename: Jennifer
authors.initials: J
authors.lastname: Blum
authors.forename: Beverly
authors.initials: B
authors.lastname: Winikoff
authors.forename: Sheila
authors.initials: S
authors.lastname: Raghavan
authors.forename: Rasha
authors.initials: R
authors.lastname: Dabash
authors.forename: Mohamed Cherine
authors.initials: MC
authors.lastname: Ramadan
authors.forename: Berna
authors.initials: B
authors.lastname: Dilbaz
authors.forename: Blami
authors.initials: B
authors.lastname: Dao
authors.forename: Jill
authors.initials: J
authors.lastname: Durocher
authors.forename: Serdar
authors.initials: S
authors.lastname: Yalvac
authors.forename: Ayisha
authors.initials: A
authors.lastname: Diop
authors.forename: Ilana G
authors.initials: IG
authors.lastname: Dzuba
authors.forename: Nguyen Thi Nhu
authors.initials: NT
authors.lastname: Ngoc
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D003906:Developing Countries; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D016595:Misoprostol / Q000008:administration & dosage*; D010120:Oxytocics / Q000008:administration & dosage*; D010121:Oxytocin / Q000008:administration & dosage*; D006473:Postpartum Hemorrhage / Q000517:prevention & control*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D010120:Oxytocics; D016595:Misoprostol; D010121:Oxytocin