Pre-eclampsia intervention with esomeprazole: the PIE trial

Pre-Eclampsia and esomeprazole in South Africa

Pre-eclampsia occurs when the placenta releases toxic substances into the mother's bloodstream, affecting vital organs such as the brain, kidneys, heart and liver. To this day, pre-eclampsia is a disease without a cure. To save the mother’s life, the placenta must be delivered and so the baby- often small, sick and premature. A drug that could reduce the release of the placental toxins would be a breakthrough in the global fight against pre-eclampsia. It could enable the pregnancy to progress safely until the baby is mature enough to be delivered. The Translational Obstetric Group, through their pre-eclampsia drug screening pipeline have discovered that Esomeprazole - known to be safe in pregnancy- could be just such a treatment.  This has now been taken to a phase II clinical trial, in a country that needs it the most - Cape Town in South Africa

Introducing the pre-eclampsia intervention with esomeprazole (PIE) trial

The Translational Obstetrics Group have identified that esomeprazole, a proton pump inhibitor used to treat gastric reflux is able to dramatically reduce the production and release of the placental toxins known to be responsible for preeclampsia. Esomeprazole also appears to improve blood vessel health, and reduce cell stress, other sentinel features of preeclampsia. Importantly, esomeprazole has a well-established safety record in pregnancy.

This laboratory evidence has been sufficiently compelling to advance esomeprazole to a Phase II clinical trial for the treatment of severe preterm preeclampsia. The University of Stellenbosch has partnered with Mercy Perinatal to undertake the Preeclampsia Intervention with Esomeprazole (PIE) trial, based in Tygerberg Hospital, Cape Town. South Africa has an extremely high rate of preterm preeclampsia, and Tygerberg Hospital is one of the few centres internationally with the necessary expertise to manage this condition and oversee an interventional trial.

The PIE trial is a double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. 120 women with severe pre-eclampsia  at a gestational age of 26+0 to 31+6 weeks will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. In settings such as Tygerberg Hospital, prolongation of pregnancy by as little as 5 days could make the difference between survival or loss of the baby

Current status

PIE commenced recruitment in January, 2016 and incredibly, over two thirds of patients have been randomised already. We expect the trial to complete recruitment in the first half of 2017, and to report by the middle of next year. A carefully curated biobank including blood and placental samples have been created from the entire PIE cohort. We expect that these precious samples will advance our understanding on the ways in which Esomeprazole works.

The team

Team members

Dr Cathy Cluver, PhD and PI for the PIE trial
Professor Stephen Tong
Professor Sue Walker
Professor Ben Mol, University of Adelaide
Professor David Hall, University of Stellenbosch
Professor Gerhard Theron, University of Stellenbosch
Ms Erika van Papendorp, Research Midwife, Tygerberg Hospital
Dr Richard Hiscock, Statistician

Data monitoring committee

Dr Jim Holberton, Mercy Hospital for Women
Professor Jonathan Morris, Kolling Institute, University of Sydney
Dr Lisa Yelland, University of Adelaide

Funding sources

Mr Geoff Handbury
Norman Beischer Medical Research Foundation
Mercy Health Foundation