INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Prophylactic Pravastatin in the Prevention of Preeclampsia and its Effects on sFlt1/PLGF Levels in Pregnant Women at High Risk of Developing Preeclampsia

ObjectivesThe study aim is to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing preeclampsia and the maternal and perinatal outcomes and the sFlt1/PLGF ratio in the Surabaya cohort of the INOVASIA trial. SettingThis study involved 2 academic hospital (a tertiary and secondary center) in Surabaya, Indonesia. ParticipantsPregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery doppler examination at 10-20 weeks gestational age. InteventionsThe control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20 mg twice daily) starting from 14-20 weeks gestation until delivery. Research blood samples were collected before the first dose of pravastatin, and just before delivery. Primary and Secondary OutcomesThe primary outcome was the rate of maternal preeclampsia, secondary outcomes included maternal-perinatal outcomes and sFlt-1, PLGF, sFlt-1/PlGF ratio and sEng levels. ResultsThe rate of preeclampsia was (non-significantly) lower in the pravastatin group compared with the control group (17.5% vs 35%). The pravastatin group also had a (non-significant) lower rate of severe preeclampsia, HELLP syndrome, acute kidney injury and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly lower (p 0.048) in the pravastatin group (n=4) compared with the controls (n=12). Neonates in the pravastatin group had significantly higher birthweights, higher Apgar scores, and lower composite neonatal morbidity and NICU admission rates. All biomarkers show a significant deterioration in the control group compared with non-significant changes in the pravastatin group. ConclusionsPravastatin holds promise in the secondary prevention of preeclampsia and placenta-mediated adverse perinatal outcomes by improving the anti-angiogenic/pro-angiogenic imbalance. Trial RegistrationClinical Trial Gov (ID: NCT03648970) Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThe largest randomized clinical trial reporting the effects of pravastatin in the prevention of preeclampsia in pregnant women at a high risk of developing preeclampsia with maternal preeclampsia as primary endpoint C_LIO_LISecondary outpoints included perinatal outcomes, and sFlt-1, PlGF, sFlt-1/PlGF ratio, and sEng levels C_LIO_LIInsufficient funding for placebo tables in the setting of Indonesia, a developing country, resulted in the trial design being an open randomized controlled trial C_LIO_LIIn order to reduce risk of bias, 2 independent MFM consultants evaluated and verified all abnormal outcomes while being blinded for group allocation of the trial participants C_LI