title: Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Postpartum haemorrhage (PPH) is a major cause of maternal morbidity. Bleeding is caused by a combination of physical causes, such as failure of the uterus to contract or operations, and is made worse by impairment of the blood clotting system. A number of studies have shown that low levels of the blood clotting factor fibrinogen are associated with progression of bleeding, the need for invasive interventions and transfusions of red blood cells and fresh frozen plasma (FFP). This trial will investigate whether early infusion of fibrinogen concentrate during a major PPH, with the aim of correcting a low fibrinogen to a level that is normal for delivery, based on the Fibtem test, reduces the total number of allogeneic blood products (red blood cells, FFP, cryoprecipitate and platelets) transfused after study medication until discharge, compared to placebo.
  
  
  METHODS
  This is a prospective, randomised, double-blind placebo controlled trial. Women will enter an observational phase and if their Fibtem levels fall they will be randomised in the interventional phase. A total of 60 women will be randomised and women are eligible for the trial if they meet all of the following inclusion criteria: age 18 years or over, gestation ≥24 + 0 weeks, haemorrhage of about 1500 ml and on-going bleeding without another complication or haemorrhage of about 1000 ml and caesarean section/uterine atony/placental abruption/placenta praevia/cardiovascular instability or microvascular oozing. Participants with a Fibtem A5 < 16 mm will be randomly allocated to receive either a bolus infusion of fibrinogen concentrate or placebo (isotonic saline). The dose of fibrinogen concentrate or placebo will be calculated based on the woman's ideal body weight for height and the measured Fibtem A5 with the aim of increasing the Fibtem A5 to 23 mm.
  
  
  CONCLUSIONS
  The trial aims to provide evidence on the efficacy and safety of fibrinogen concentrate during acute bleeding in an obstetric setting.
  
  
  BACKGROUND
  ISRCTN ref: ISRCTN46295339 (01.07.2013); EudraCT: 2012-005511-11 (28.11.2012), UKCRN ref: 13940.
authors.affiliation: Innovation, Methodology and Engagement, South East Wales Trials Unit, Institute of Translation, Cardiff University School of Medicine, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. aawarn@cf.ac.uk.
authors.forename: Nadine
authors.initials: N
authors.lastname: Aawar
authors.affiliation: Department of Haematology, Cardiff and Vale University Health Board, Cardiff, UK. raza.alikhan@wales.nhs.uk.
authors.forename: Raza
authors.initials: R
authors.lastname: Alikhan
authors.affiliation: Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Cardiff, UK. danielbruynseels@doctors.org.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bruynseels
authors.affiliation: Innovation, Methodology and Engagement, South East Wales Trials Unit, Institute of Translation, Cardiff University School of Medicine, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. CanningsRL@cardiff.ac.uk.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cannings-John
authors.affiliation: Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Cardiff, UK. rachel.collis@wales.nhs.uk.
authors.forename: Rachel
authors.initials: R
authors.lastname: Collis
authors.affiliation: Department of Anaesthetics, University College Hospital, London, UK. john.dick@uclh.nhs.uk.
authors.forename: John
authors.initials: J
authors.lastname: Dick
authors.affiliation: Department of Anaesthetics, Leicester Royal Infirmary, Leicester, UK. chris.d.elton@uhl-tr.nhs.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Elton
authors.affiliation: Department of Anaesthetics, University College Hospital, London, UK. r.fernando@btinternet.com.
authors.forename: Roshan
authors.initials: R
authors.lastname: Fernando
authors.affiliation: Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Cardiff, UK. hallj@wales.nhs.uk.|Institute of Infection and Immunity, Critical Illness Research Group, Cardiff University School of Medicine, Cardiff, UK. hallj@wales.nhs.uk.
authors.forename: Judith
authors.initials: J
authors.lastname: Hall
authors.affiliation: Innovation, Methodology and Engagement, South East Wales Trials Unit, Institute of Translation, Cardiff University School of Medicine, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. hoodk1@cf.ac.uk.
authors.forename: Kerry
authors.initials: K
authors.lastname: Hood
authors.affiliation: Department of Obstetrics, University College Hospital, London, UK. nicki.lack@uclh.nhs.uk.
authors.forename: Nicki
authors.initials: N
authors.lastname: Lack
authors.affiliation: Department of Anaesthetics, Liverpool's Women's Hospital, Liverpool, UK. shuba.mallaiah@nhs.net.
authors.forename: Shuba
authors.initials: S
authors.lastname: Mallaiah
authors.affiliation: Department of Obstetrics, Leicester Royal Infirmary, Leicester, UK. Helena.j.maybury@uhl-tr.nhs.uk.
authors.forename: Helena
authors.initials: H
authors.lastname: Maybury
authors.affiliation: Innovation, Methodology and Engagement, South East Wales Trials Unit, Institute of Translation, Cardiff University School of Medicine, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. NuttallJ@cardiff.ac.uk.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Nuttall
authors.affiliation: Institute of Primary Care and Public Health, Cardiff University School of Medicine, Cardiff, UK. ParanjothyS@cf.ac.uk.
authors.forename: Shantini
authors.initials: S
authors.lastname: Paranjothy
authors.affiliation: Department of Obstetrics, Cardiff and Vale University Health Board, Cardiff, UK. rachel.rayment@wales.nhs.uk.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rayment
authors.affiliation: Department of Obstetrics, Cardiff and Vale University Health Board, Cardiff, UK. alexandra.rees2@wales.nhs.uk.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rees
authors.affiliation: Innovation, Methodology and Engagement, South East Wales Trials Unit, Institute of Translation, Cardiff University School of Medicine, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. sandersj3@cardiff.ac.uk.|Department of Obstetrics, Cardiff and Vale University Health Board, Cardiff, UK. sandersj3@cardiff.ac.uk.
authors.forename: Julia
authors.initials: J
authors.lastname: Sanders
authors.affiliation: Innovation, Methodology and Engagement, South East Wales Trials Unit, Institute of Translation, Cardiff University School of Medicine, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. townson@cardiff.ac.uk.
authors.forename: Julia
authors.initials: J
authors.lastname: Townson
authors.affiliation: Department of Women's and Children's Health, University of Liverpool, Liverpool, UK. aweeks@liverpool.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Weeks
authors.affiliation: Department of Haematology, Cardiff and Vale University Health Board, Cardiff, UK. peter.collins@wales.nhs.uk.|Institute of Infection and Immunity, Critical Illness Research Group, Cardiff University School of Medicine, Cardiff, UK. peter.collins@wales.nhs.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D001780:Blood Coagulation Tests; D001803:Blood Transfusion; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D005340:Fibrinogen / Q000008:administration & dosage* / Q000009:adverse effects; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007263:Infusions, Parenteral; D006473:Postpartum Hemorrhage / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011247:Pregnancy; D011446:Prospective Studies; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014852:Wales; D055815:Young Adult
chemical_list: D006490:Hemostatics; D005340:Fibrinogen