A multi-centre phase IIa clinical study of predictive testing for preeclampsia: improved pregnancy outcomes via early detection (IMPROvED)

Abstract

Background: 5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia.

Methods/design: We report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks' gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit.

Discussion: The IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If 'at risk' patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome.

Trial registration: Trial registration number NCT01891240The IMPROvED project is funded by the seventh framework programme for Research and Technological development of the EU. http://www.fp7-improved.eu/

Figures

Figure 1

Flowchart of IMPROvED visits and pregnancy outcome data.

Figure 2

The effect of study design on sample size calculations and conclusions that can be drawn from screening studies. (A) Women are randomised to having or not having the screening test performed. (B) Women have the screening test performed and those who screen as high risk are randomised to having an intervention or having the result concealed.