A Randomized Controlled Trial of Pravastatin to Prevent Preeclampsia in High Risk Women
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 102
- 试验地点
- 12
- 主要终点
- Proportion of Participants With Composite of Preeclampsia, Fetal Loss and Maternal Death
研究概览
简要总结
This study is a double-blind randomized placebo-controlled trial of 1,550 high-risk women to assess whether daily treatment with pravastatin administered early in pregnancy reduces the rate of a composite outcome of preeclampsia, fetal loss and maternal death. Women with a prior history of preeclampsia with preterm delivery less than 34 weeks will be randomized to pravastatin or placebo daily until delivery. Women will have monthly study visits during pregnancy, a follow-up visit at 6 weeks postpartum and children will have follow-up visits at 2 and 5 years of age.
详细描述
Preeclampsia complicates approximately 3% to 5% of pregnancies and remains a major cause of maternal and neonatal morbidities and mortality. Women who experience preeclampsia in one pregnancy are at higher risk of developing preeclampsia in a subsequent pregnancy than those who have never experienced the condition. There is evidence from laboratory studies and clinical trials, as well as biological plausibility, to suggest that statins may prevent the development of preeclampsia by reversing various pathways associated with preeclampsia. Pravastatin has a favorable safety profile and pharmacokinetic properties.
The study is a randomized placebo-controlled multi-center clinical trial of 1,550 women with a prior history of preeclampsia that required delivery at less than 34 weeks, randomized to either 20mg pravastatin or an identical appearing placebo daily until delivery. Women with a singleton or twin gestation will be randomized between 12 weeks 0 days and 16 weeks 6 days will be followed monthly during pregnancy and then at 6 weeks postpartum. Children will have follow-up visits at 2 and 5 years of age to assess growth, cognition, behavior, motor skills, vision and hearing.
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
- Double (Participant, Investigator)
盲法说明
Consenting women will be assigned to pravastatin or placebo in a 1:1 ratio according to a randomization sequence prepared and maintained centrally by the Data Coordinating Center (DCC). The two study medication arms of the study (pravastatin or placebo) are double masked; neither the patient nor the clinical staff will be aware of the treatment assignment.
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •16 years or older at time of consent with ability to give informed consent
- •Single or twin gestation with cardiac activity in one or both fetuses. Higher order multifetal gestations reduced to twins, either spontaneously or therapeutically, are not eligible unless the reduction occurred by 13 weeks 6 days project gestational age.
- •Gestational age at randomization between 12 weeks 0 days and 16 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
- •Documented history (by chart or delivery/operative note review) of prior preeclampsia with delivery less than or equal to 34 weeks 0 days gestation in any previous pregnancy. If in the index pregnancy, the woman was induced by 34 weeks 0 days gestation and delivered within 48 hours in the same hospitalization, that woman would be eligible.
- •Normal serum transaminase (AST/ALT) concentrations documented in the last 6 months.
排除标准
- •Monoamniotic gestation because of the risk of fetal demise
- •Known chromosomal, genetic or major malformations
- •Fetal demise or planned termination of pregnancy. Selective reduction by 13 weeks 6 days gestation, from triplets to twins or twins to singleton is not an exclusion.
- •Contraindications for statin therapy:
- •Hypersensitivity to pravastatin or any component of the product
- •Active liver disease: acute hepatitis or chronic active hepatitis
- •Statin use in current pregnancy
- •Patients with any of the following medical conditions:
- •Uncontrolled hypothyroidism with a TSH level above 10 mIU/L, because of increased risk of myopathy
- •HIV positive, because of increased risk of myopathy with use of protease inhibitors
- •Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL, because of association with adverse pregnancy outcomes
- •Current use of concomitant medication with potential for drug interaction with statins (i.e.,, cyclosporine, fibrates, niacin, erythromycin). Patients will not be excluded if the drug is discontinued (at least one week) prior to randomization.
- •Participating in another intervention study that influences the primary outcome in this study
- •Plan to deliver in a non-network site
- •Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
研究组 & 干预措施
Pravastatin
20 mg pravastatin daily
干预措施: Pravastatin (Drug)
Placebo
Identical appearing daily placebo
干预措施: Placebo (Other)
结局指标
主要结局
Proportion of Participants With Composite of Preeclampsia, Fetal Loss and Maternal Death
时间窗: 48 hours postpartum
Proportion of participants demonstrating a composite of preeclampsia, fetal loss, or maternal death. 1. Baseline Normotensive: a) Severe hypertension (HTN) or b) Mild HTN w/ any of the following: i.) New-onset proteinuria or doubling in protein w/ baseline proteinuria ii.) Thrombocytopenia iii.) Progressive renal insufficiency iv). Impaired liver function v.) Pulmonary edema vi.) New-onset \& persistent cerebral or visual symptoms 2. Baseline chronic HTN: any of the following a)Severe HTN b) New onset proteinuria or doubling in protein from baseline proteinuria c)Thrombocytopenia d) Progressive renal insufficiency e) Impaired liver function f) Pulmonary edema g) New-onset \& persistent cerebral or visual symptoms. 3. HELLP a) Hemolysis AND b)Thrombocytopenia AND c) AST/ALT ≥ 70 IU/L 4. Atypical HELLP an occurrence of 2 of the 3: a) Hemolysis, b)Thrombocytopenia, OR c) AST/ALT ≥ 70 IU/L 5. Eclampsia 6. Competing outcomes: maternal death before delivery or fetal loss \< 20wks, 0 days
次要结局
- Proportion of Participants With Preeclampsia With Severe Features(48 hours postpartum)
- Proportion of Participants With Gestational Hypertension(48 hours postpartum)
- Proportion of Participants With Pregnancy Associated Hypertension(48 hours postpartum)
- Proportion of Participants With Postpartum Preeclampsia(48 hours postpartum through 6 weeks post partum)
- Proportion of Participants With Gestational Diabetes(At any time during pregnancy through delivery (up to approximately 30 weeks))
- Rate of Adherence to Study Medication(Randomization to delivery (up to approximately 30 weeks))
- Proportion of Participants With Severe Maternal Morbidity Composite(Randomization through 6 weeks postpartum)
- Length of Maternal Hospital Stay(Delivery admission through discharge from the hospital (a median of 3 days))
- Rate of Adverse Events of Special Interest (AESI) or Serious AESI(Randomization through 48 hours postpartum)
- Gestational Age at Delivery(Delivery)
- Proportion of Participants With Preterm Birth < 37 Weeks(Delivery before 37 weeks)
- Proportion of Participants With Indicated Preterm Birth < 37 Weeks(Delivery before 37 weeks)
- Proportion of Participants With Preterm Birth < 34 Weeks(Delivery before 34 weeks)
- Proportion of Fetal or Neonatal Deaths(randomization (mother) through 28 days of life (neonate))
- Birth Weight(Birth)
- Proportion of Small for Gestational Age < 5th Percentile(Birth)
- Proportion of Small for Gestational Age < 10th Percentile(Birth)
- Proportion of NICU/Intermediate Nursery Admission(Birth through hospital discharge (an average of 4 days))
- NICU/Intermediate Nursery Length of Stay(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates Needing Mechanical Ventilation or Continuous Positive Airway Pressure (CPAP)(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates Needing Oxygen Support(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates With Respiratory Distress Syndrome(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates With Bronchopulmonary Dysplasia(28 days of life and 36 weeks corrected gestational age)
- Proportion of Neonates With Necrotizing Enterocolitis(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates With Intraventricular Hemorrhage(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates With Periventricular Leukomalacia (PVL)(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates Experiencing Early Onset Sepsis(Birth to 72 hours from birth)
- Proportion of Neonates Experiencing Late Onset Sepsis(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates With Retinopathy of Prematurity(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates With Composite Neonatal Outcome(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates Experiencing Seizures(Birth through hospital discharge (an average of 4 days))
- Proportion of Neonates With a Congenital Anomaly / Birth Defect(Randomization through delivery (up to approximately 30 weeks))
- Neonatal Auditory Brain Stem Response (ABR)/Otoacoustic Emissions (OAE)(Birth through hospital discharge (an average of 4 days))
- BMI for Age at 24 Corrected Months(24 months of age)
- Cognitive Standard Score From the Bayley Certified Scales of Infant Development III Edition at 24 Months of Age(24 months of age)
- Motor Standard Score From the Bayley Certified Scales of Infant Development III Edition at 24 Months of Age(24 months of age)
- Language Standard Score From the Bayley Certified Scales of Infant Development III Edition at 24 Months of Age(24 months of age)
- Gross Motor Function Classification System at 24 Months of Age(24 months of age)
- Proportion of Children With Hearing Loss at 24 Months of Age(24 months of age)
- Child Behavior Checklist Total Problems T-Score at 24 Months(24 months of age)
- Proportion of Children With Vision Problems at 24 Months of Age(24 months of age)