Preeclampsia intervention trials

Preeclampsia and esomeprazole in South Africa

Pre-eclampsia is a disease of pregnancy that occurs when the placenta releases toxic substances into the mother's bloodstream. These toxins can affect vital organs such as the brain, kidneys, heart and liver. To this day, pre-eclampsia is a disease without a cure. 

A drug that could treat preeclampsia would be a major breakthrough for the health of women and babies. The Translational Obstetric Group at Mercy Perinatal have discovered a number of drugs that have the potential to treat severe preeclampsia.

Mercy Perinatal has been working closely with friends at Tygerberg Hospital, Cape Town, South Africa to test candidate drugs in a series of randomised clinical trials, called the ‘PI’ Trials (Preeclampsia intervention).

Our first trial - PIE

South Africa has an extremely high rate of severe preeclampsia. Dr Cathy Cluver,  a maternal fetal medicine specialist based in Cape Town, worked closely with Mercy Perinatal to evaluate whether esomeprazole could treat severe preeclampsia. 

The PIE trial was a double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily could prolong gestation in women with early onset pre-eclampsia. PIE commenced recruitment early in 2016 and incredibly was complete in just over 12 months (2017). We published the trial findings in October this year in the American Journal of Obstetrics and Gynaecology. A carefully curated biobank including blood and placental samples have been created from the entire PIE cohort as well. We expect that these precious samples will advance our understanding of esomeprazole and how it might help in the fight against preeclampsia.

Our second trial - PI2

In 2016, we discovered that metformin may be a candidate treatment for preeclampsia. Given this, the team has now commenced PI2 (Preeclampsia Intervention 2). It is a randomised clinical trial also based at Tygerberg Hospital and similar in design to PIE. A pharmacokinetic study was done on 20 participants prior to the start of PI2, and this showed excellent results in the circulation of women with preterm preeclampsia. 

PI2 Trial started recruiting at the beginning of 2018. By November 2018, it had already recruited 60 out of the planned 150 participants. At this pace, it should be finished by early 2020 and we will find out the results then.

Future trials

We envisage it will be difficult to find a drug that can slow the disease progression once preterm preeclampsia has taken hold - it is the most severe variant of preeclampsia. 

However, the Mercy Perinatal team members working across Melbourne and Cape Town are determined to try. They will patiently run a succession of PI trials in the hope they will discover an effective drug to treat pre-eclampsia, saving the lives of mothers and their babies. 

The PI trials structure is globally unique. No other team has such a set up that allows them to test drugs in successive clinical trials to find one that may be effective for preterm preeclampsia.

The team

Team members

Dr Cathy Cluver, University of Stellenbosch, Cape Town
Professor Stephen Tong
Professor Sue Walker
Professor Ben Mol, Monash University
Professor David Hall, University of Stellenbosch, Cape Town
Dr Natalie Hannan
Dr Richard Hiscock, Statistician

Funding sources

Mr Geoff Handbury
Norman Beischer Medical Research Foundation
Mercy Health Foundation