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.
The trial protocol is available here 
The published trial is available here 
Daily esomeprazole (40 mg) did not prolong gestation in pregnancies with preterm preeclampsia or decrease circulating soluble fms-like tyrosine kinase 1 concentrations.

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 findings from the PI2 trial have not yet been confirmed in a European population. Therefore, we have planned the multicenter PI4 trial in Sweden. This trial is aiming to start recruitment in the end of 2023. Women diagnosed with preterm preeclampsia at seven sites in Sweden will be included. These include Falun, Uppsala, Karolinska Solna, Karolinska Huddinge, Sahlgrenska, Malmö and Lund. We are aiming to recruit 294 women and they will be randomised to metformin or placebo.