Management of Postpartum Haemorrhage and Effect of Geographic Region

Postpartum Hemorrhage Clinical Trial

Official title:

Management of Postpartum Haemorrhage and Effect of Geographic Region: A Secondary Analysis of the World Maternal Antifibrinolytic (WOMAN) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03166839
• Other study ID #: 12049
• Status: Completed
• Phase: N/A
• First received: May 24, 2017
• Last updated: May 25, 2017
• Start date: March 2009
• Est. completion date: May 2017

Study information

• Verified date: May 2017
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: Maternal deaths occur universally and are largely avoidable. Postpartum haemorrhage accounts for a disproportionate amount of maternal deaths. There remains a great need to expeditiously decrease the rate of postpartum haemorrhage to prevent further mortality.

Methods: This study is a cohort analysis of data collected for the pragmatic international multi-centre randomized double blind placebo controlled design WOMAN Trial. It will present a univariate analysis of patient and delivery characteristics (age, type of delivery, placenta fully delivered, primary cause of haemorrhage, severity of haemorrhage), physiologic characteristics (systolic blood pressure, estimated blood loss, clinical signs of haemodynamic instability) and management characteristics (receipt of blood products, uterotonics). Multivariable logistic regression models and likelihood ratio tests will be used to examine the evidence for interaction between death from PPH and region after adjusting for any independent effects of 1) systolic blood pressure 2)age 3) type of delivery 4) receipt of blood products Discussion: This analysis of the WOMAN trial dataset will explore the relationship between geographical location, patient and environment characteristics and outcomes of postpartum haemorrhage. A protocol and statistical analysis plan is presented here.

Description:

Global burden of disease Maternal deaths occur universally and are largely avoidable(1). According to the first publication of the Maternal Health Series published in the Lancet October 2016, approximately 300,000 maternal deaths occurred in the past year. Postpartum haemorrhage was the cause of one tenth of these deaths(2,3). While this number has decreased globally since 1990, haemorrhage still accounts for a disproportionate amount of maternal deaths. There remains a great need to expeditiously decrease the rate of postpartum haemorrhage to prevent further mortality.

Why study postpartum haemorrhage? The most severe outcome of postpartum haemorrhage (PPH) is the death of a mother. The World Health Organization defines maternal death as "death of a woman while pregnant or within 42 days of termination of pregnancy" (4). The clinical definition of postpartum haemorrhage refers to more than 500mL of blood loss after a vaginal delivery and more than 1000mL after a caesarean section(5). Haemorrhage is a rapidly fatal condition, most commonly caused by uterine atony, or the inability of the uterus to contract, constricting the network of vessels in the uterine muscle, gradually slowing active bleeding. For this reason, research efforts have been directed at minimizing or preventing uterine atony through preventative or treatment measures targeted at the third stage of labour(6,7). Anti-fibrinolytics have been proposed as an alternative method of slowing bleeding and have been studied both as a prophylactic intervention and a treatment modality(8-11). Risk of death from postpartum haemorrhage increases if the woman is anaemic as she cannot tolerate blood loss to the same extent that her counterparts with normal haemoglobin levels can(3,12). Recent publication of preliminary findings of the woman trial suggest that the anti-fibrinolytic tranexamic acid may reduce maternal mortality from PPH by over one third(13).

Why stratify by region? While the absolute number of maternal deaths around the world is impressive, quoting a global rate does not accurately reflect the burden of illness in different regions of the world. In developed countries like the United States of America, the risk of dying from postpartum haemorrhage after delivering a live baby is 13.4% (pooled, range: 4.7-34.6). This stands in stark contrast to the African experience, where studies have documented maternal death rates from PPH to be as high as 33.9% (pooled, range: 13.3-43.5)(14). There are other reasons why these numbers can vary so broadly. An obvious hypothesis is that more women die from postpartum haemorrhage in developing countries than their counterparts in developed countries because it is more prevalent, more severe or is managed differently than in other parts of the world. It has been proposed, however, that the different rates in fact reflect a paucity of reliable data that is region specific. This is indeed the case when we look at the continent of Africa, where studies done to date capture only the experiences of eight of the 54 countries on the continent (Egypt in the North, Senegal in the West, and the Democratic Republic of Congo, South Africa, Tanzania, Zambia, Zimbabwe in the East and South)(14). A third factor in estimating deaths from postpartum haemorrhage reflects the different birthing environments across regions. In some countries, up to 50% of women deliver at home with support from a traditional birth attendant and never access a medical clinic or hospital. When most women do not deliver in a hospital or clinic, they do not die in a hospital or clinic so their data goes largely unregistered(9). Despite the fact that the "poorest countries have the poorest data"(12) enough is known about postpartum haemorrhage to inform action and spur further investigation, as many organizations have done(15).

While developing countries carry a higher burden of maternal deaths from postpartum haemorrhage, the impact of maternal death from PPH does not spare the developed world(14). Haemorrhage remains a leading cause of maternal death in countries where the majority of deliveries are performed in hospital with highly skilled support(16). This may be, in part, due to the unpredictability of postpartum haemorrhage, even in low-risk women(12). Risk factors for postpartum haemorrhage are commonly accepted to include previous postpartum haemorrhage, pre-eclampsia, disorders of the placenta, induction or augmentation of labour, perineal trauma, high birthweight and retained products(7)(16). Further, reporting occurrence of postpartum haemorrhage varies due to varying definitions of blood loss, the way blood loss is measured, intra-partum management strategies including uterotonics, uterine massage, and cord traction, interventions including method of delivery as well as the underlying characteristics of the population being studied(6)(3). Much time and resources have been invested in investigating the use of uretonics such as oxytocin to treat the most common causes of postpartum haemorrhage(7).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20060
• Est. completion date: May 2017
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Women aged 16 years and older

• Clinical diagnosis of postpartum haemorrhage (PPH) after vaginal delivery or caesarean section

• "clinical uncertainty" about benefit of tranexamic acid in addition to routine management of PPH

Exclusion Criteria:

• Women aged 16 years and older with a clinical diagnosis of postpartum haemorrhage with clear indication or contra-indication for tranexamic acid

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Hemorrhage

Intervention

Other:
• Experiencing PPH
No intervention given

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine

References & Publications (13)

Begley CM, Gyte GM, Devane D, McGuire W, Weeks A. Active versus expectant management for women in the third stage of labour. Cochrane Database Syst Rev. 2015 Mar 2;(3):CD007412. doi: 10.1002/14651858.CD007412.pub4. Review. — View Citation

Calvert C, Thomas SL, Ronsmans C, Wagner KS, Adler AJ, Filippi V. Identifying regional variation in the prevalence of postpartum haemorrhage: a systematic review and meta-analysis. PLoS One. 2012;7(7):e41114. doi: 10.1371/journal.pone.0041114. Epub 2012 Jul 23. Review. — View Citation

Carroli G, Cuesta C, Abalos E, Gulmezoglu AM. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol. 2008 Dec;22(6):999-1012. doi: 10.1016/j.bpobgyn.2008.08.004. Epub 2008 Sep 25. Review. — View Citation

Gohel, M Efficacy of tranexemic acid in decreasing blood loss during and after cesarean section: A randomised case controlled prospective study. J Obstet Gynecol India. 2007;57(3):227-30.

Graham W, Woodd S, Byass P, Filippi V, Gon G, Virgo S, Chou D, Hounton S, Lozano R, Pattinson R, Singh S. Diversity and divergence: the dynamic burden of poor maternal health. Lancet. 2016 Oct 29;388(10056):2164-2175. doi: 10.1016/S0140-6736(16)31533-1. Epub 2016 Sep 16. Review. — View Citation

Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006 Apr 1;367(9516):1066-74. Review. — View Citation

McClure EM, Jones B, Rouse DJ, Griffin JB, Kamath-Rayne BD, Downs A, Goldenberg RL. Tranexamic acid to reduce postpartum hemorrhage: A MANDATE systematic review and analyses of impact on maternal mortality. Am J Perinatol. 2015 Apr;32(5):469-74. doi: 10.1055/s-0034-1390347. Epub 2014 Oct 7. Review. — View Citation

Mousa HA, Blum J, Abou El Senoun G, Shakur H, Alfirevic Z. Treatment for primary postpartum haemorrhage. Cochrane Database Syst Rev. 2014 Feb 13;(2):CD003249. doi: 10.1002/14651858.CD003249.pub3. Review. — View Citation

Mousa HA, Cording V, Alfirevic Z. Risk factors and interventions associated with major primary postpartum hemorrhage unresponsive to first-line conventional therapy. Acta Obstet Gynecol Scand. 2008;87(6):652-61. doi: 10.1080/00016340802087660. — View Citation

Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2015 Jun 16;(6):CD007872. doi: 10.1002/14651858.CD007872.pub3. Review. — View Citation

Ronsmans C, Graham WJ; Lancet Maternal Survival Series steering group.. Maternal mortality: who, when, where, and why. Lancet. 2006 Sep 30;368(9542):1189-200. Review. — View Citation

Shakur H, Roberts I, Edwards P, Elbourne D, Alfirevic Z, Ronsmans C. The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial. Trials. 2016 May 17;17(1):249. doi: 10.1186/s13063-016-1332-2. — View Citation

WOMAN Trial Collaborators.. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	Death due to bleeding from PPH	Within 42 days of delivery