Title: A randomised controlled trial of intra-operative cell salvage during caesarean section in women at risk of haemorrhage.
Funder: Department of Health (England)

Abstract: DESIGN: Multicentre individual randomised controlled trial with cost-effectiveness analysis. We have already demonstrated the feasibility of individual randomisation in the pilot study. SETTING: At least 16 large UK obstetric units in collaboration with The Pragmatic Clinical Trials Unit (PCTU) at Barts and the London School of medicine. TARGET POPULATION: Women at increased risk of haemorrhage during CS including previous CS; emergency CS; and abnormal placentation. Women with a contraindication to cell salvage e.g. sickle cell disease malignancy religious belief will be excluded. 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 and the dose of anti-D antibody administered. 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. ECONOMIC ANALYSIS: Economic evaluation will include cost per blood transfusion and inpatient day avoided and costs of quality of life improvement. The economic evaluation will be carried out from the perspective of the NHS including only direct medical costs. PROJECT TIMETABLES INCLUDING RECRUITMENT RATE: Research ethics approval has already been obtained for the pilot study at Birmingham Women’s Hospital (Northern and Yorkshire MREC ref number 08/H0903/33). A substantial amendment will be submitted before commencement of the project. 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 two years would require each of the 16 units to contribute 96 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.


Research activity codes: 6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH