Intramuscular oxytocin versus oxytocin/ergometrine versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: study protocol for a randomised controlled trial (the IMox study)

Helen van der Nelson, Stephen O'Brien, Erik Lenguerrand, Elsa Marques, Mary Alvarez, Michelle Mayer, Sara Burnard, Dimitrios Siassakos, Timothy Draycott, Helen van der Nelson, Stephen O'Brien, Erik Lenguerrand, Elsa Marques, Mary Alvarez, Michelle Mayer, Sara Burnard, Dimitrios Siassakos, Timothy Draycott

Abstract

Background: Postpartum haemorrhage remains a major cause of maternal mortality and morbidity worldwide. Active management of the third stage of labour reduces the risk of postpartum haemorrhage. Oxytocin and oxytocin/ergometrine are commonly used in the UK, with oxytocin/ergometrine being more effective at preventing moderate, but not severe, blood loss. Many guidelines specifically recommend using oxytocin for all vaginal births, as it is associated with fewer adverse events. However, a survey conducted by the Southmead Hospital Maternity Research Team revealed that 71.4% of UK obstetric units still routinely use oxytocin/ergometrine. Carbetocin is a newer medication that may be as effective but has fewer side effects. No studies have directly compared all three medications.

Methods: The IMox study aims to determine the most effective, acceptable and cost-effective drug for primary prevention of postpartum haemorrhage following vaginal birth. The IMox study is a prospective, multi-centre, double-blind, randomised trial directly comparing oxytocin, oxytocin/ergometrine and carbetocin given intramuscularly for the prevention of postpartum haemorrhage in the third stage of labour. The primary effectiveness outcome is the use of an additional uterotonic drug. Secondary effectiveness outcomes reflect maternal morbidity and mortality within the immediate postpartum period. Participant questionnaires and subjective reporting of side effects will be used to evaluate maternal acceptability. Maternal quality of life utilities will be collected antenatally, and on days 1 and 14 after birth to enable a cost-effectiveness assessment of each studied drug. Participants will be pregnant women planning a vaginal birth in six hospitals in England. Participants will be approached and invited to provide consent to participate from 20 weeks gestation until in established labour. A complete sample of 5712 participants (1904 per arm) providing data for the primary outcome will allow for a robust determination of efficacy between all three study drugs. Data will be collected until participants are discharged from the hospital and on postnatal days 1 and 14 regardless of location. All analyses will be on a modified intention-to-treat basis, and additionally repeated on a per protocol basis. Data collection commenced in Feburary 2015 and was completed in August 2018.

Discussion: This study is the first to directly compare oxytocin, oxytocin/ergometrine and carbetocin in the same population for the prevention of postpartum haemorrhage following vaginal birth. Furthermore, this study will be the first to directly compute health economic outcomes from such a three-way comparison. This study is limited to using short-term outcomes, and so will not provide evidence for important outcomes such as long-term maternal psychological well-being and time to next conception.

Trial registration: ClinicalTrials.gov, NCT02216383 . Registered on 18 August 2014. EudraCT, 2014-001948-37. Registered on 23 September 2014. ISRCTN, ISRCTN10232550. Retrospectively registered on 6 March 2018).

Keywords: Carbetocin; Oxytocin; Oxytocin/ergometrine; Postpartum haemorrhage; Prevention; Primary.

Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

The IMox study has been approved by the South Central – Oxford B Research Ethics Committee, UK on 28 October 2014, reference number 14/SC/1312, the Medicines and Healthcare products Regulatory Agency on 30 October 2014 and the Health Research Authority on 3 August 2016. Written consent has been gained antenatally from all trial participants. Consent may be withdrawn at any time without a reason being stated.

Consent for publication

Not applicable.

Competing interests

TD has acted as a consultant for Ferring Pharmaceuticals Ltd. DS has received sponsorship to attend two conferences from Ferring Pharmaceuticals Ltd. and is a member of their GLOBE Personal Development Scheme. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT diagram of the IMox study
Fig. 2
Fig. 2
Participant timeline for the IMox study
Fig. 3
Fig. 3
SPIRIT diagram for the IMox study

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Source: PubMed

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