The Preeclampsia Intervention Trials

Preterm preeclampsia is a devastating disease for which there is currently no treatment apart from delivery. Finding a treatment for preterm preeclampsia could save many lives and improve outcomes for mothers and babies. The Preeclampsia Intervention (PI) trials are double blinded randomized control trials that are run to assess novel therapeutics. Pregnant women with preterm preeclampsia who are being managed expectantly are invited to participate.

PIE trial (Preeclampsia Intervention with esomeprazole trial)
Our first trial assessed 40mg of esomeprazole daily to prolong pregnancy in preterm preeclampsia at Tygerberg Hospital, Cape Town South Africa. We included 120 women with preterm preeclampsia.Daily esomeprazole (40 mg) did not prolong gestation in pregnancies with preterm preeclampsia or decrease circulating soluble fms-like tyrosine kinase 1 concentrations.
The trial protocol is available here
The published trial is available here 

PI 2 trial (Preeclampsia Intervention 2 with metformin)
Our second trial assessed 3 grams of metformin in divided doses in 180 women with preterm preeclampsia at Tygerberg Hospital, Cape Town, South Africa. Excitingly, metformin use was associated with a 7-day prolongation. The PI 2 trial suggests that extended-release metformin can prolong gestation in women with preterm preeclampsia, although further
trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible.
The trial protocol is available here
The published article is available here

PI3 trial (Preeclampsia Intervention 3 with metformin)
We are currently recruiting women into this trial. This trial will include 500 women diagnosed with preterm preeclampsia at Tygerberg Hospital, Cape Town, South Africa. We are assessing metformin to prolongation of gestation and this trial is also powered to neonatal outcomes.
The trial registration can be found here

PI4 trial (Preeclampsia Intervention 4 with metformin)
The results of the PI2 study have not yet been confirmed in a European population. Therefore, we have now started a multicenter metformin trial in Sweden, the PI4 trialThe trial aims to evaluate whether metformin can prolong pregnancy, increase birth weight and reduce time in the neonatal unit for the baby. Women diagnosed with early preeclampsia at seven clinics in Sweden (Falun, Uppsala, Karolinska Solna, Karolinska Huddinge, Sahlgrenska, Malmö and Lund) will be randomized to metformin or placebo between 2024 and 2027. We aim to recruit 294 women in total.