Pravastatin to Prevent Preeclampsia and Reduce Maternal-Neonatal Mortality and Morbidity in High Risk Preeclampsia Patients
试验速览
- 阶段
- 2 期
- 入组人数
- 280
- 试验地点
- 7
- 主要终点
- Preeclampsia
研究概览
简要总结
BACKGROUND Preeclampsia is a major cause of maternal and neonatal morbidity worldwide. There is currently no cure for preeclampsia, the only definitive treatment is termination of pregnancy by induction of labour or caesarean section. Statin has been proposed to represent a new approach to improve disease outcome/prevent preeclampsia based on its multilayered activity toward pregnancy protection, including: protection of vascular endothelial cells survival, induce expression of heme oxygenase 1 (HO-1), inhibiting the release of soluble FMS-like tirosine kinase-1 (sFlt-1) and soluble endoglin (sEng), two main culprits in the pathophysiology of preeclampsia.
OBJECTIVE The aim of this study is to observe the effect of pravastatin administration in patients with high risk of preeclampsia in order to reduce maternal and neonatal mortality and morbidity.
METHODS This is a prospective randomized controlled clinical trial. The research will be held in 5 maternal fetal medicine centers in Indonesia (multicenter study). The recruitment will be done by permuted block random sampling methods, with sample size around 280 patients divides into two group. Patients with high risk of preeclampsia will be randomized either to get pravastatin 2 x 20 mg per oral and aspirin 1 x 80 mg (treatment group) or low dose aspirin only (control group). The patient will be followed regularly until delivery to obtain detailed maternal and neonatal outcome.
OUTCOME Primary Outcomes: Maternal preeclampsia, severe preeclampsia, gestational hypertension, indicated preterm delivery less than 37 weeks, indicated preterm delivery less than 34 weeks, maternal complications, length of hospital stay, and any serious adverse event.
Secondary Outcomes: Composite fetal/neonatal mortality and morbidity (stillbirth, neonatal death, respiratory distress syndrome, intracerebral hemorrhage, neonatal sepsis, intra uterine growth restriction [Small for Gestational Age (SGA) < 5th centile], and necrotizing enterocolitis), birthweight, birthweight percentile, level of care (well baby, intermediate, NICU), NICU length of stay, ventilator usage, and length of perinatal hospital stay.
KEYWORDS: pravastatin, preeclampsia, neonatal mortality, neonatal morbidity
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
The diagnosis is made by resident unaware of the medication patients received
入排标准
- 年龄范围
- 15 Years 至 45 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Gestational Age 10 wk - 19 wk 6 day
- •History of previous preeclampsia requiring birth < 37 weeks (risk 30%), or
- •Patients with a combination of at least 2 major risk factors plus an abnormal uterine artery Doppler at 11-20 weeks gestation (risk preeclampsia 30%):
- •Major clinical risk factors (Obesity, strong family history of preeclampsia [mother or sister], maternal age > 40 years old, chronic hypertension, Policystic Ovarian Syndrome (PCOS), Chronic kidney disease, diabetes mellitus, multiple pregnancies, first pregnancy, pregnancy interval more than 10 years, new partner/husband, Reproductive technologies (IVF pregnancy), heritable thrombophilias, Booking Blood pressure >130/80 mmHg, family history of early onset cardiovascular disease, lower socioeconomic status)
- •Abnormal uterine artery Doppler defined as (Second trimester screening:
- •average resistance index > 0.58 and/or or early-diastolic diastolic notch. First trimester screening: Pulsatility index > 95th centile or PI > 1.5) or:
- •First trimester screening (11+0 to 14+1 weeks): Combination of maternal risk factors, elevated MAP, and increased Uterine artery pulsatility index (UTPI).
- •Second trimester screening (19+0 to 24+6 weeks): Combination of maternal risk factors, elevated MAP, and increased Uterine artery pulsatility index (UTPI).
- •Combination of elevated mean arterial pressure (MAP > 90 mmHg) in the second trimester with abnormal uterine artery Doppler
- •Combination elevated booking blood pressure (> 130/85 mmHg) with abnormal uterine artery Doppler
- •Live fetus, no detectable fetal anomaly
排除标准
- •Condition where the pregnancies should be terminated within 48 hours, on the basis of any indication (patients consume pravastatin less than 2 days).
- •Contraindication to the statin use:
- •Hypersensitivity to pravastatin
- •Active liver disease
- •Pre pregnant renal insufficiency/kidney failure (history of hemodialysis)
- •Current use of statin
- •Participation in any other controlled trial of investigational medical products in pregnancy
研究组 & 干预措施
Pravastatin Treatment Group
In this arm, the participant will be given aspirin 80 mg daily per oral and the study drugs, Pravastatin 2 x 20 mg per oral daily.
干预措施: Pravastatin (Drug)
结局指标
主要结局
Preeclampsia
时间窗: From date of randomization until date of delivery
Including preeclampsia, preeclampsia with severe features, and gestational hypertension.
Preterm delivery
时间窗: 20 - 34 weeks, and 34 - 37 weeks
Including indicated preterm delivery \< 34 weeks and \< 37 weeks
Maternal complication
时间窗: From date of randomization until date of delivery
Any maternal complication caused by preeclampsia: eclampsia, seizure, HELLP syndrome, acute pulmonary edema, acute kidney injury, Cardivascular accident, liver failure, sepsis, and pneumonia
次要结局
- Perinatal outcome(At delivery)
- Composite neonatal morbidity and mortality(At delivery)
研究者
Muhammad Ilham Aldika Akbar, MD, OBGYN
Principal Investigator, MFM Consultant
Universitas Airlangga