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
Authors: Aldika Akbar Muhammad Ilham , Yosediputra Angelina , Pratama Raditya Eri , Fadhilah Nur Lailatul , Sulistyowati  , Amani Fariska Zata , Ernawati  , Dachlan Erry Gumilar , Angsar Muhammad Dikman , Dekker Gus 
Published: June 2021

Objectives

The 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.

Setting

This study involved 2 academic hospital (a tertiary and secondary center) in Surabaya, Indonesia.

Participants

Pregnant 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.

Inteventions

The 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 Outcomes

The 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.

Results

The 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.

Conclusions

Pravastatin holds promise in the secondary prevention of preeclampsia and placenta-mediated adverse perinatal outcomes by improving the anti-angiogenic/pro-angiogenic imbalance.

Trial Registration

Clinical Trial Gov (ID: NCT03648970)

Article Summary

Strengths and limitations of this study

The 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

Secondary outpoints included perinatal outcomes, and sFlt-1, PlGF, sFlt-1/PlGF ratio, and sEng levels

Insufficient funding for placebo tables in the setting of Indonesia, a developing country, resulted in the trial design being an open randomized controlled trial

In 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