ORCID Profile
0000-0001-9571-0715
Current Organisation
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 30-06-2020
DOI: 10.1186/S13063-020-04441-9
Abstract: The E-Freeze trial is a multi-centre randomised controlled trial of fresh versus frozen embryo transfer for women undergoing in vitro fertilisation. This paper describes the statistical analysis plan for the E-Freeze trial. E-Freeze is a two-arm parallel-group, multi-centre, in idually randomised controlled trial to determine if a policy of freezing embryos, followed by thawed frozen embryo transfer, results in a higher healthy baby rate when compared with the current policy of transferring fresh embryos. Couples undergoing their first, second or third cycle of in vitro fertilisation at fertility centres in the UK were randomised to either fresh or frozen embryo transfer. The primary outcome is a healthy baby, defined as a live singleton baby born at term with an appropriate weight for gestation. This paper describes the statistical analysis plan for the trial, including the analysis principles, definitions of outcomes, methods for primary analysis, pre-specified subgroup analysis and sensitivity analysis. This plan was finalised prior to completion of recruitment to the trial. ISRCTN registry: ISRCTN61225414 . Registered on 29 December 2015.
Publisher: National Institute for Health and Care Research
Date: 12-2020
DOI: 10.3310/EME07090
Abstract: Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and raised serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment, but without an adequate evidence base. We aimed to evaluate whether or not ursodeoxycholic acid reduces adverse perinatal outcomes in affected women. Multicentre, masked, randomised, placebo-controlled, two-arm, parallel-group trial. Thirty-three UK maternity units. Women with intrahepatic cholestasis of pregnancy aged ≥ 18 years, between 20 +0 and 40 +6 weeks’ gestation with a singleton or twin pregnancy and no known lethal fetal anomaly. Women were randomly assigned (1 : 1 allocation ratio) to take ursodeoxycholic acid tablets or matched placebo tablets, at an equivalent dose of 1000 mg daily, titrated as needed. The primary outcome was a composite of perinatal death (in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery ( 37 weeks’ gestation) or neonatal unit admission for at least 4 hours (from birth until hospital discharge). Each infant was counted once within this composite. Analyses were by intention to treat. Between 23 December 2015 and 7 August 2018, 605 women were randomised, with 305 women allocated to the ursodeoxycholic acid arm and 300 women to the placebo arm. There was no evidence of a significant difference in the incidence of the primary outcome between the groups: 23.0% (74 out of 322 infants) in the ursodeoxycholic acid group compared with 26.7% (85 out of 318 infants) in the placebo group adjusted risk ratio 0.85 (95% confidence interval 0.62 to 1.15). There was no evidence of a significant difference in total costs (maternal, infant and the cost of ursodeoxycholic acid) between the two trial groups. There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group. Limitations include a primary outcome event rate in the control group that was lower than that estimated for the s le size calculation, but the lack of evidence of effect in all analyses suggests that it is unlikely that the trial had insufficient power. In this clinical trial of ursodeoxycholic acid in women with intrahepatic cholestasis of pregnancy, there is no evidence that it is effective in reducing a composite of adverse perinatal outcomes. Future research should aim to elucidate the aetiology and pathophysiology of adverse perinatal outcomes, particularly stillbirth, in women with intrahepatic cholestasis of pregnancy to assist the development of an effective preventative treatment. Further exploratory analyses may identify groups of women who might respond to ursodeoxycholic acid treatment. Current Controlled Trials ISRCTN91918806. This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation Vol. 7, No. 9. See the NIHR Journals Library website for further project information.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jennifer Bell.