Browsing by Author "Sujata Misra"

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Heat-stable carbetocin versus oxytocin to prevent hemorrhage after vaginal birth
(Massachussetts Medical Society, 2018) Mariana Widmer; Gilda Piaggio; Thi M.H. Nguyen; Alfred Osoti; Olorunfemi O. Owa; Sujata Misra; Arri Coomarasamy; Hany Abdel-Aleem; Ashalata A. Mallapur; Zahida Qureshi; Pisake Lumbiganon; Archana B. Patel; Guillermo Carroli; Bu-Kola Fawole; Shivaprasad S. Goudar; Yeshita V. Pujar; James Neilson; G. Justus Hofmeyr; Lin L. Su; Jose Ferreira De Carvalho; Uma Pandey; Kidza Mugerwa; Shobha S. Shiragur; Josaphat Byamugisha; Daniel Giordano; A.M. Gülmezoglu
BACKGROUND Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin. METHODS We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively. RESULTS A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups. CONCLUSIONS Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. Copyright © 2018 Massachusetts Medical Society.
Heat-Stable Carbetocin Versus Oxytocin to Prevent Hemorrhage after Vaginal Birth
(Lippincott Williams and Wilkins, 2018) Mariana Widmer; Gilda Piaggio; Thi M.H. Nguyen; Alfred Osoti; Olorunfemi O. Owa; Sujata Misra; Arri Coomarasamy; Hany Abdel-Aleem; Ashalata A. Mallapur; Zahida Qureshi; Pisake Lumbiganon; Archana B. Patel; Guillermo Carroli; Bukola Fawole; Shivaprasad S. Goudar; Yeshita V. Pujar; James Neilson; G. Justus Hofmeyr; Lin L. Su; Jose Ferreira De Carvalho; Uma Pandey; Kidza Mugerwa; Shobha S. Shiragur; Josaphat Byamugisha; Daniel Giordano; A. Metin Gülmezoglu
Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage,which is not available in many countries, and has unsatisfactory real-world efficacy as a result of heat sensitivity and quality issues such as insufficient active ingredient or impurities. Heat-stable carbetocin, an oxytocin analogue, does not require cold-chain transport and storage; it has been shown to maintain stability over a period of 36 months at 30°C and 75% relative humidity. Although there have been trials of carbetocin, most of the trials involved women undergoing cesarean delivery, were small, were of varied quality, and used an intravenous route of administration. The researchers conducted an international, randomized, double-blind, active-controlled noninferiority trial comparing the effects of heat-stable carbetocin with those of oxytocin on postpartum hemorrhage after vaginal birth at 23 hospitals (sites) in 10 countries between July 2015 and January 2018. Women who expected to give birth vaginally and who had a singleton pregnancy and cervical dilatation of 6 cm or less were eligible.Women were randomly assigned to receive a single intramuscular injection of either heat-stable carbetocin at a dose of 100 μg or oxytocin at a dose of 10 IU. Immediately after delivery, the drugwas administered and the management of the third stage of labor was conducted as recommended in theWorldHealth Organization guidelines. A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 mL or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95-1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 mL was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87-1.25), with the CI crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the 2 groups. Heat-stable carbetocinwas noninferior to oxytocin for the prevention of blood loss of at least 500 mL or the use of additional uterotonic agents. Low event rates for blood loss of at least 1000 mL limited the power of the trial to investigate that outcome. © 2018 Wolters Kluwer Health, Inc. All rights reserved.