Full title: A randomised controlled trial of intra-operative cell salvage during caesarean section in women at risk of haemorrhage
Centres: Centre for Primary Care and Public Health.
Research Groups: Pragmatic Clinical Trials Unit
Research status: Recruiting
Donated blood is a precious resource. Its availability is an essential prerequisite for major procedures including joint replacement, cardiac surgery, organ transplantation, cancer care and the management of major trauma. Its scarcity places constant limitations on the ability of the NHS to deliver high quality health care to all points of need simultaneously. Priority decisions result in the deferment or cancellation of procedures if this resource is required elsewhere.
Intraoperative cell salvage (IOCS) collects the patient's own blood lost during an operation, cleans it and returns it to their circulation. It reduces the amount of donor blood given in certain operations. Its use in Caesarean section has not yet been adequately examined due in part to concerns about contamination of salvaged blood with amniotic fluid, which have proven unfounded. Donor blood transfusion carries with it significant risks, which IOCS has the potential to avoid, including cross-matching errors, infection and transfusion reaction. The National Institute of Clinical Excellence (NICE) recommends IOCS for massive blood loss in an emergency, but has called for robust evidence from clinical trials to support its routine use. This study will assess if IOCS during Caesarean section reduces the need to give a donor blood transfusion. Around 3050 women at risk of bleeding will be studied. As many women as possible booked at around 22 large obstetric units will be given information about the study, prior to birth. Those who deliver by Caesarean section will be asked if they would like to participate. Half will be randomly allocated IOCS during surgery, and half to receive standard care with donor blood transfusion if necessary. The necessity for transfusion will be recorded for each group. Other maternal health and cost outcomes will be collected. The research team is hand-picked from regional centres across England, Scotland and Wales and includes national experts in obstetrics, anaesthesia, cell salvage, health technology assessment and health economics. Team members have an established track record in the successful design, conduct and analysis of large multicentre randomised trials which have changed clinical practice. A UKCRN registered trials unit will support the study. The majority of costs incurred to perform this study will be to employ dedicated research personnel at the recruiting centres. Investment to confirm or refute the value of IOCS will benefit women in childbirth now and save NHS resources in the future.
Professor Khalid Khan, Professor of Women's Health & Clinical Epidemiology, Blizard Institute, Centre for Primary Care and Public Health, Queen Mary, University of London, Email: firstname.lastname@example.org
Dr Philip Moore, Consultant, Anaesthetics, University Hospitals Birmingham NHS Foundation Trust Email: email@example.com
Dr Matthew Wilson MA (Oxon) BM ChB MD FRCA Consultant Anaesthetist, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Email: firstname.lastname@example.org
Dr James Geoghegan, Consultant, Anaesthetics, University Hospitals Birmingham NHS Foundation Trust, Email: email@example.com
Ms Jane Daniels, Senior Research Fellow/Deputy Director (BCTU), Birmingham Clinical Trials Unit, University of Birmingham Email: firstname.lastname@example.org
Ms Samantha Parker, Consumer representation, National Childbirth Trust, Email: email@example.com
Dr Sue Catling, Consultant Anaesthetist, Anaesthetics, ABMU-LHB NHS Trust, Singleton Hospital, Swansea, Email: firstname.lastname@example.org
Dr Paul Ayuk, Consultant, Obstetrics and Gynaecology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Email: email@example.com
Ms Mairi Harkness, Transfusion Specialist Midwife, Better Blood Transfusion, Scottish National Blood Transfusion Service, Email: firstname.lastname@example.org
Dr Ian James Wrench, Consultant, Anaesthetics, Sheffield Teaching Hospitals NHS Foundation Trust Email: Ian.Wrench@sth.nhs.uk
Professor Fang Gao-Smith, Professor, Health Sciences Research Institute, University of Warwick Email: Fang.Gao@warwick.ac.uk
Barts Health NHS Trust, Royal London Hospital
Dr Matthew Hogg MB, ChB, MRCOG, Consultant in Obstetrics and Gynaecology (obstetric lead), Women's Centre, Royal London Hospital, Email: email@example.com
Birmingham Women's NHS Foundation Trust
Dr James Geoghegan MB, ChB, FRCA, Consultant Anaesthetist, Dept of Anaesthesia, Queen Elizabeth Hospital Birmingham, Email:firstname.lastname@example.org
Heart of England Foundation Trust
Dr Elizabeth Walker, Dept of Anaesthetics, Bordesley Green East, Email: Elizabeth.Walker@heartofengland.nhs.uk
Newcastle Hospitals NHS Trust
Dr Paul Ayuk, Consultant Obstetrician, Directorate Of Women's Services, Newcastle-Upon-Tyne Hospitals NHS Trust, Email: email@example.com
Nottingham City Hospital
Dr Lesley Woods, Dept of Anaesthetics, Hucknall Road, Nottingham, Email: firstname.lastname@example.org
Dr Vinod Patil MBBS FRCA, Consultant Anaesthetist, Anaesthesia Dept, Queens Hospital, Email: email@example.com
Royal Hallamshire Hospital, Sheffield
Dr Ian Wrench MBChb, BMedSci, PhD, FRCA, Consultant Anaesthetist, Department of Anaesthesia, C Floor, Outpatient department, Royal Hallamshire Hospital, Email: Ian.Wrench@sth.nhs.uk
Simpson Centre for Reproductive Health, Edinburgh
Dr Arlene Wise MBChB, FRCA, Consultant Anaesthetist, Dept of Anaesthesia, Email: firstname.lastname@example.org
Singleton Hospital Swansea
Dr Susan Williams FRCA, Consultant Anaesthetist, Singleton Hospital, Email: email@example.com
Whipps Cross University Hospital
Sunderland Royal Hospital
Dr Aarti Ullal, MRCOG, Sunderland Royal Hospital, Aarti.Ullal@chsft.nhs.uk
Royal United Hospital
Dr Chris Marsh MBChB, FRCA, Department of Anaesthesia, Royal United Hospital Bath, firstname.lastname@example.org
Leicester University Hospitals
Dr Hatem Mousa (Tommy), MD,MD, MRCOG, MSc, MBBCh, Leicester Royal Infirmary, email@example.com
Chelsea and Westminster Hospital NHS Foundation Trust
Dr DominikaDabrowska,MD,WestMiddlesex University Hospital, Dominika.Dabrowska@wmuh.nhs.uk
Dr Darryl Thorp-Jones, BSc, MBBS, FRCA, Derriford Hospital, Plymouth,
University Hospitals of North Midlands NHS Trust
Dr Jules Allt, MBChB, FRCA, Royal Stoke University Hospital
Croydon University Hospital
Dr Bini Ajay, MBBS, MRCOG,MFSRH , Croydon University Hospital
Dr Sangeeta Pathak, MBBS, M.Med, DFFP, MRCOG, MD
Consultant Obstetrician, Hinchingbrooke Hospital, Huntingdon, PE29 6NT
James Cook University Hospital
Dr Sanjay Rao, MD,MRCOG,MRCPI,DNBE,Dip ClinEd, The James Cook University Hospital, South Tees NHS Foundation Trust, Middlesbrough
Northwick Park Hospital
Dr Parijat Bhattacharjee, MRCOG, North West London Hospitals NHS Trust, Harrow
Dr Peter Yoxall, MB ChB FRCA, St Helens and Knowsley Teaching Hospitals NHS Trust, Prescot
Norfolk and Norwich University Hospital
Dr Jonathon Francis, MBChB FRCA MRCS, Norfolk and Norwich University Hospital, Norwich
Women's Health Research Unit
Professor Khalid Khan - Professor of Women's Health and Clinical Epidemiology
0207 882 2621 / 07977 559 415, Email: firstname.lastname@example.org
Malika Barakat - Data and Admin Assistant for SALVO, 020 7882 6694, Email: email@example.com
James Heighway - Data and Admin Assistant for SALVO, 020 7882 3275, Email: firstname.lastname@example.org
PCTU Statistician: Lee Beresford, Email: email@example.com
Design: Multicentre individual randomised controlled trial with cost-effectiveness analysis.
Setting: At least 17 large UK obstetric units in collaboration with The Pragmatic Clinical Trials Unit (PCTU) at Bart's and the London School of Medicine.
Women who are admitted to a participating labour ward who fulfil all the following criteria will be eligible to be randomised:
- 16 years of age or older
- Delivery by elective or emergency caesarean section with an identifiable increased risk of haemorrhage.
- Ability to provide informed consent
- Elective first Caesarean section for maternal request or breech presentation
- Sickle cell disease
- Active malignancy contraindicated to CS e.g. abdominal cancer
- Cultural or social beliefs contraindicating blood transfusion e.g. Jehovah's Witnesses
- Significant antibodies making it difficult to find cross matched blood for transfusion
- Unable to understand written and spoken English
Health Technologies Being Assessed:
Intra-operative Cell Salvage (IOCS): A technique which allows the blood lost during surgery to be returned to the patient. Blood is aspirated from the surgical field; the red cell component isolated by centrifugation and after washing and filtration, re-transfused. The ability to return salvaged blood is dependent on sufficient volume being collected and processed. Blood will be uniformly returned to women in the cell salvage group if this volume threshold is reached. The control group will receive current practice (without cell salvage) which may involve donor blood transfusion. It is not possible to conduct a blinded study, since group allocation will be self-evident. In life threatening acute haemorrhage, women will be managed at the discretion of attending clinicians, in line with Centre for Maternal and Child Enquiries (CMACE) guidance, potentially including the use of cell salvage in the control arm. The indications for postoperative donor blood transfusion will be set according to local protocols in each hospital and deviations from this criterion will be monitored.
Measurement of costs and outcomes:
The need for blood transfusion will be recorded, including blood given after CS to treat anaemia. The volume of blood returned by IOCS will be recorded. Pre and post-operative haemoglobin estimation is standard practice for CS. These values will be used to calculate mean fall in haemoglobin level. Postnatal outcomes will include time to first mobilisation, length of hospital stay, multi-decimal fatigue inventory and the dose of anti-D antibody administered. We will also record the resources used intra- and post-operatively, including IOCS consumables and donor blood transfusions along with any issues preventing the use of IOCS such as technical failure. The costs of staff training, service procurement and provision of care will be collected alongside clinical outcomes.
Sample size and analysis:
Estimating baseline transfusion rate for CS is problematic since published data varies widely from 1.8% to 23.5%. Contemporary observational reports put this figure at around 5% in current UK practice. This is supported by audit data from proposed trial centres. Since the study population is at risk of haemorrhage, a denominator transfusion requirement of 5% represents a conservative estimate for the control arm. Estimating the effect of cell salvage on transfusion requirement is supported by evidence from 2 systematic reviews of trials utilising IOCS in non-obstetric operative interventions which both suggest a relative risk of exposure to donated blood of 0.6. An intervention effect of IOCS based on this would reduce transfusion requirement from 5% to 3%. A trial to detect this difference with 80% power (2 sided alpha) would require a total of 3050 women.
The aim of the economic evaluation is to determine the relative cost-effectiveness of the IOCS compared to current practice. The economic evaluation will be carried out from the perspective of the NHS therefore only direct costs and outcomes to the health service associated with the intervention will be included in the analysis and these direct costs will include those associated with adverse events. The evaluation will consider costs incurred by the health service in the delivery of the alternative treatment pathways and given the duration of follow up in the trial is for the immediate post natal period until discharge from hospital, it is a pragmatic decision to limit the perspective to the NHS. There is no reason to expect the alternative strategies to cause significant variation in the private costs to individuals, or to society, between the arms of the study beyond this time point, so wider costs such as primary data on the private out of pocket costs to individuals associated with the study will not be collected.
Project timetables including recruitment rate:
We anticipate it will take 6 months to recruit research staff and obtain LREC and research governance approval for the sites involved. A recruitment target of 3050 over 2 years would require each of the 17 units to contribute 90 women per year. This conservative estimate is reasonable considering the challenges of recruiting women in labour. A data monitoring committee will report every 6 months to an independent trial steering committee. Data entry and analysis, economic evaluation, dissemination of research findings and report writing will take 6 months. The total length of the study will therefore be 3 years.