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Esomeprazole to treat women with preterm preeclampsia: a randomized placebo controlled trial

      Background

      Preterm preeclampsia has a high rate of fetal death or disability. There is no treatment to slow the disease, except delivery. Preclinical studies have identified proton pump inhibitors as a possible treatment.

      Objective

      The purpose of this study was to examine whether esomeprazole could prolong pregnancy in women who have received a diagnosis of preterm preeclampsia.

      Study Design

      We performed a double-blind, randomized controlled trial at Tygerberg Hospital in South Africa. Women with preterm preeclampsia (gestational age 26 weeks+0 days to 31 weeks+6 days) were assigned randomly to 40-mg daily esomeprazole or placebo. The primary outcome was a prolongation of gestation of 5 days. Secondary outcomes were maternal and neonatal outcomes. We compared circulating markers of endothelial dysfunction that was associated with preeclampsia and performed pharmacokinetic studies.

      Results

      Between January 2016 and April 2017, we recruited 120 participants. One participant was excluded because of incorrect randomization, which left 59 participants in the esomeprazole and 60 participants in the placebo group. Median gestational age at enrolment was 29+4 weeks gestation. There were no between-group differences in median time from randomization to delivery: 11.4 days (interquartile range, 3.6–19.7 days) in the esomeprazole group and 8.3 days (interquartile range, 3.8–19.6 days) in the placebo group (3 days longer in the esomeprazole arm; 95% confidence interval, –2.9–8.8; P=.31). There were no placental abruptions in the esomeprazole group and 6 (10%) in the placebo group (P=.01, P=.14 adjusted). There were no differences in other maternal or neonatal outcomes or markers of endothelial dysfunction. Esomeprazole and its metabolites were detected in maternal blood among those treated with esomeprazole, but only trace amounts in the umbilical cord blood.

      Conclusion

      Daily esomeprazole (40 mg) did not prolong gestation in pregnancies with preterm preeclampsia or decrease circulating soluble fms-like tyrosine kinase 1 concentrations. Higher levels in the maternal circulation may be needed for clinical effect.

      Key words

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      Linked Article

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        American Journal of Obstetrics & GynecologyVol. 220Issue 2
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          Sandrim et al advises caution in evaluating proton pump inhibitors (PPI) to treat preeclampsia, in light of their prior work, suggesting PPI may have actions that could increase blood pressure, by interfering with nitric oxide (NO) homeostasis.
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      • Esomeprazole to treat women with preeclampsia: possible implications in the nitric oxide homeostasis
        American Journal of Obstetrics & GynecologyVol. 220Issue 2
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          We read with interest the article by Cluver et al1 evaluating the use of proton pump inhibitor (PPI) esomeprazole to treat women with preterm preeclampsia.1 While the 40 mg of daily oral esomeprazole tested in their study did not prolong gestation in pregnancies with preterm preeclampsia or decrease circulating soluble fms-like tyrosine kinase-1 concentrations, the authors discuss that this dosage of esomeprazole may be too low to treat preterm preeclampsia and suggest that higher doses may still be effective.
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