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34: Th Pre-eclampsia Intervention with Esomeprazole trial (PIE trial)

      Objective

      Preeclampsia is a major pregnancy complication globally responsible for thousands of deaths. We have shown in preclinical studies that esomeprazole can potently decrease sFlt secretion and mitigate endothelial dysfunction. We therefore set out to examine whether esomeprazole could prolong pregnancy in women diagnosed with very preterm preeclampsia.

      Study Design

      We performed a double blind, randomised, placebo controlled trial at Tygerberg Hospital in South Africa. Women with a singleton pregnancy who were diagnosed with preterm preeclampsia (gestational age (GA) of 26+0 to 31+6) were randomised (stratified to GA above or below 29 weeks) to 40 mg daily esomeprazole or an identical placebo until delivery. The primary outcome was prolongation of gestation. Secondary outcomes included maternal and neonatal composites and individual outcomes. Serial samples were taken for circulating sFlt and other biomarker levels. Pharmacokinetics were performed on 19 participants. To assess whether esomeprazole would prolong the gestation with an additional 5 days we needed to recruit 120 women.

      Results

      Between January 2016 and April 2017 we randomised 120 women. One participant was excluded due to incorrect randomisation (59 esomeprazole vs 60 placebo). Baseline characteristics were comparable with a median GA at enrolment of 29+4 weeks in both groups. Median time from randomisation to delivery was 12.9 days in the esomeprazole group versus 13.1 days in the placebo group (P-value 0,92, Figure 1). Secondary outcomes are shown in Table 1. There was a statistically significant reduction in the incidence of abruptio placenta (0/59 vs 6/60 esomeprazole vs placebo (p=0.01)). sFlt1 levels among both arms were very high, with no difference between the groups on serial samples, no obvious decline (or further increase) among either group, and a rapid decline post delivery. In the intervention group, esomeprazole was detectable in maternal blood and the cord blood levels were extremely low.

      Conclusion