Back to resultsPravastatin to Prevent Preeclampsia (Pravastatin)
Primary Purpose
Preeclampsia, Obstetric Labor Complications, Hypertension in Pregnancy
Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Pravastatin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Preeclampsia focused on measuring Pregnancy, Preeclampsia
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- University of Alabama - Birmingham
- Northwestern University
- Columbia University
- University of North Carolina - Chapel Hill
- Case Western Reserve-Metro Health
- Ohio State University Hospital
- Hospital of the University of Pennsylvania
- Magee Women's Hospital of UPMC
- Brown University
- University of Texas Medical Branch
- University of Texas - Houston
- University of Utah Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Pravastatin
Placebo
Arm Description
20 mg pravastatin daily
Identical appearing daily placebo
Outcomes
Primary Outcome Measures
Proportion of participants with composite of preeclampsia, fetal loss and maternal death
Proportion of participants demonstrating a composite of preeclampsia, fetall
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
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.
HELLP a) Hemolysis AND b)Thrombocytopenia AND c) AST/ALT ≥ 70 IU/L
Atypical HELLP an occurrence of 2 of the 3: a) Hemolysis, b)Thrombocytopenia, OR c) AST/ALT ≥ 70 IU/L
Eclampsia
Competing outcomes: maternal death before delivery or fetal loss < 20wks, 0 days
Secondary Outcome Measures
Proportion of participants with preterm birth < 37 weeks
Preterm birth before 37 weeks gestation
Proportion of participants with indicated preterm birth < 37 weeks
Indicated preterm birth less than 37 weeks
Proportion of participants with preterm birth < 34 weeks
Preterm birth before 34 weeks gestation
Proportion of participants with preeclampsia with severe features
Preeclampsia with severe features as defined by the American College of Obstetricians and Gynecologists (ACOG) diagnostic criteria (i.e., severe hypertension, thrombocytopenia, impaired liver function, progressive renal insufficiency, pulmonary edema, new-onset and persistent cerebral or visual symptoms)
Proportion of participants with Postpartum Preeclampsia
Preeclampsia that occurs 48 hours or more after birth
Proportion of participants with Gestational hypertension
Defined as new onset hypertension in the absence of accompanying proteinuria or other features of preeclampsia
Proportion of participants with pregnancy associated hypertension
Defined as gestational hypertension or preeclampsia
Proportion of participants with Gestational diabetes
Gestational diabetes mellitus
Rate of Adherence to study medication
Adherence to the medication regimen for the study (daily pill)
Rate of Adverse Events of Special Interest (AESI)
Adverse events of Special Interest (AESI) including myalgia and muscle weakness, and serious AESI defined as maternal myositis, myopathy, rhabdomyolysis, or serious liver injury
Gestational age at delivery
Gestational age at the time of delivery
Length of maternal hospital stay
Length of maternal hospital stay for the delivery admission and number and length of maternal hypertension related and overall hospitalizations during the pregnancy
Concentrations of angiogenic factors
Concentrations of angiogenic factors (sFlt-1, sEng, and PlGF)
Concentrations of cholesterol and triglycerides
Concentrations of cholesterol (total, low density lipoprotein, high density lipoprotein) and triglycerides
Proportion of participants with Severe maternal morbidity composite
A composite of severe maternal morbidity of either maternal death, eclampsia, HELLP syndrome, cerebral vascular accident, heart failure, myocardial infarction, acute respiratory distress syndrome requiring mechanical ventilation, disseminated intravascular coagulopathy, pulmonary edema, renal failure, liver rupture, or placental abruption
Percentage of Fetal or neonatal deaths
Death of the fetus or neonate
Birth weight
Birth weight and rate of "small for gestational age" as measured by birth weight: a) < 5th percentile and b) < 10th percentile for gestational age
NICU/intermediate nursery admission
Admission to the neonatal intensive care unit (NICU) or intermediate nursery
NICU/intermediate nursery length of stay
Length of stay in the neonatal intensive care unit (NICU) and/or intermediate nursery
Proportion of neonates needing Mechanical ventilation
Mechanical ventilation in the first 72 hours of life and duration
Proportion of neonates needing oxygen support
Provision of oxygen support for the neonate and duration
Proportion of neonates with Respiratory Distress Syndrome
Respiratory distress syndrome (RDS), defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with an oxygen requirement and confirmed by a chest x-ray
Proportion of neonates with Bronchopulmonary Dysplasia
Bronchopulmonary dysplasia (BPD), defined as oxygen requirement at 28 days of life and at 36 weeks corrected gestational age
Proportion of neonates with Necrotizing Enterocolitis
Necrotizing enterocolitis (NEC), defined as modified Bell Stage 2 (clinical signs and symptoms with pneumatosis intestinalis on radiographs) or Stage 3 (advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation)
Proportion of neonates with Intraventricular Hemorrhage
Intraventricular hemorrhage (IVH) grade III-IV
Proportion of neonates with Periventricular leukomalacia (PVL)
Periventricular leukomalacia (PVL), diagnosed by neuroimaging
Proportion of neonates with Retinopathy of prematurity
Retinopathy of prematurity (ROP) stage III or higher
Proportion of neonates experiencing sepsis
Neonatal sepsis (within 72 hours and > 72 hours after birth). The diagnosis of sepsis will require the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebral spinal fluid (CSF), or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection.
Proportion of neonates with Composite Neonatal Outcome
Fetal or neonatal death, RDS, Grade III-IV IVH, PVL, Stage 2 or 3 NEC, BPD, Stage III or higher ROP, or early onset sepsis
Proportion of neonates experiencing seizures
Neonatal seizure activity
Proportion of neonates with a Congenital anomaly / birth defect
Congenital anomaly or birth defect excluding any conditions that must have been present before randomization
Neonatal auditory brain stem response (ABR)/Otoacoustic Emissions (OAE)
Neonatal auditory brain stem response (ABR)/Otoacoustic Emissions (OAE)
BMI for age at 24 corrected months and 5 years
Body mass index for age at 24 corrected months and 5 years using Centers for Disease Control (CDC) pediatric growth charts
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Bayley Certified Scales of Infant Development III Edition scores for cognitive, motor and language abilities at 24 months of age.
Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160. Results can also be expressed as percentile ranks relative to the standardization sample, with a mean and median of 50 and range from 1 to 99
Gross Motor Function at 24 months
Level from the Gross Motor Function Classification System at 24 months of age
Proportion of children with Hearing loss or vision problems at 24 months of age
Hearing loss or vision problems (severe nearsightedness or farsightedness, and eye movement problems) at 24 months of age
Child Behavior Checklist Total Problems Score and Syndrome Scale at 24 months and 5 years
Total problems score and syndrome scale (emotionally reactive, anxious/depressed, somatic complaints, withdrawn, attention problems, aggressive behavior) scores from the Child Behavior Checklist at 24 months and 5 years of age
The CBCL is filled out by the caregiver. Each of the 100 questions indicates a behavior for which the caregiver scores as Not True (0), Sometimes True (1), or Often True (2). The scores for all the questions are then summed and evaluated against the normative data/T-scores. A T-score of less than 60 is considered to be in the normal range. A T-score of 60-63 is a borderline, and a T-score of more than 63 is in the clinical range. Lower scores represent better outcomes.
Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)
Overall general conceptual ability score (GCA)and subscale (verbal ability, non-verbal reasoning ability, and spatial ability) scores from the Differential Ability Scales at 5 years of age
Classification:
≥ 130 Very high;120-129 High;110-119 Above average; 90-109 Average; 80-89 Below average;70-79 Low; ≤ 69 Very low
Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite score at 5 years
Assess executive function behaviors in the school and home environments with the BRIEF, a questionnaire developed for parents and teachers of school-age children. Designed to assess the abilities of a broad range of children and adolescents, the BRIEF is useful when working with children who have learning disabilities and attention disorders, traumatic brain injuries, lead exposure, pervasive developmental disorders, depression, and other developmental, neurological, psychiatric, and medical conditions.
Raw scores are converted to T-scores. Higher T-scores indicate greater impairment.
For all BRIEF2 clinical scales and indexes, T-scores from 60 to 64 are considered mildly elevated, and T-scores from 65 to 69 are considered potentially clinically elevated. T-scores at or above 70 are considered clinically elevated.
Vineland Adaptive Behavior Scales - Adaptive Behavior Composite Score at 5 years
Adaptive Behavior Composite score and domain (communication, daily living skills, socialization and motor skills) scores from the Vineland Adaptive Behavior Scale at 5 years of age. Higher scores indicate better functioning.
Domain and ABC Standard Score Ranges High 130 to 140 Moderately High 115 to 129 Adequate 86 to 114 Moderately Low 71 to 85 Low 20 to 70
Visual acuity and strabismus at 5 years
Visual acuity and strabismus from visual assessment at 5 years
Full Information
NCT ID
NCT03944512
First Posted
May 7, 2019
Last Updated
September 13, 2023
Sponsor
The George Washington University Biostatistics Center
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT03944512
Brief Title
Pravastatin to Prevent Preeclampsia
Acronym
Pravastatin
Official Title
A Randomized Controlled Trial of Pravastatin to Prevent Preeclampsia in High Risk Women
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 17, 2019 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Washington University Biostatistics Center
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preeclampsia, Obstetric Labor Complications, Hypertension in Pregnancy
Keywords
Pregnancy, Preeclampsia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
The study is a randomized controlled multi-center clinical trial of 1,550 women with a prior history of preeclampsia that required delivery at less than or equal to 34 weeks 0 days gestation, randomized to one of two arms at participating Maternal Fetal Medicine Units Network clinical centers.
20 mg pravastatin daily
Identical appearing daily placebo
Masking
ParticipantInvestigator
Masking Description
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.
Allocation
Randomized
Enrollment
1550 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pravastatin
Arm Type
Experimental
Arm Description
20 mg pravastatin daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Identical appearing daily placebo
Intervention Type
Drug
Intervention Name(s)
Pravastatin
Intervention Description
20 mg Pravastatin taken daily
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Identical appearing placebo pill
Primary Outcome Measure Information:
Title
Proportion of participants with composite of preeclampsia, fetal loss and maternal death
Description
Proportion of participants demonstrating a composite of preeclampsia, fetall
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
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.
HELLP a) Hemolysis AND b)Thrombocytopenia AND c) AST/ALT ≥ 70 IU/L
Atypical HELLP an occurrence of 2 of the 3: a) Hemolysis, b)Thrombocytopenia, OR c) AST/ALT ≥ 70 IU/L
Eclampsia
Competing outcomes: maternal death before delivery or fetal loss < 20wks, 0 days
Time Frame
48 hours postpartum
Secondary Outcome Measure Information:
Title
Proportion of participants with preterm birth < 37 weeks
Description
Preterm birth before 37 weeks gestation
Time Frame
Delivery before 37 weeks
Title
Proportion of participants with indicated preterm birth < 37 weeks
Description
Indicated preterm birth less than 37 weeks
Time Frame
Delivery before 37 weeks
Title
Proportion of participants with preterm birth < 34 weeks
Description
Preterm birth before 34 weeks gestation
Time Frame
Delivery before 34 weeks
Title
Proportion of participants with preeclampsia with severe features
Description
Preeclampsia with severe features as defined by the American College of Obstetricians and Gynecologists (ACOG) diagnostic criteria (i.e., severe hypertension, thrombocytopenia, impaired liver function, progressive renal insufficiency, pulmonary edema, new-onset and persistent cerebral or visual symptoms)
Time Frame
48 hours postpartum
Title
Proportion of participants with Postpartum Preeclampsia
Description
Preeclampsia that occurs 48 hours or more after birth
Time Frame
48 hours postpartum through 6 weeks post partum
Title
Proportion of participants with Gestational hypertension
Description
Defined as new onset hypertension in the absence of accompanying proteinuria or other features of preeclampsia
Time Frame
48 hours postpartum
Title
Proportion of participants with pregnancy associated hypertension
Description
Defined as gestational hypertension or preeclampsia
Time Frame
48 hours postpartum
Title
Proportion of participants with Gestational diabetes
Description
Gestational diabetes mellitus
Time Frame
At any time during pregnancy through delivery (up to 30 weeks)
Title
Rate of Adherence to study medication
Description
Adherence to the medication regimen for the study (daily pill)
Time Frame
Randomization to delivery (up to 30 weeks)
Title
Rate of Adverse Events of Special Interest (AESI)
Description
Adverse events of Special Interest (AESI) including myalgia and muscle weakness, and serious AESI defined as maternal myositis, myopathy, rhabdomyolysis, or serious liver injury
Time Frame
Randomization through 48 hours postpartum
Title
Gestational age at delivery
Description
Gestational age at the time of delivery
Time Frame
Delivery
Title
Length of maternal hospital stay
Description
Length of maternal hospital stay for the delivery admission and number and length of maternal hypertension related and overall hospitalizations during the pregnancy
Time Frame
Randomization through discharge from the hospital (through study completion)
Title
Concentrations of angiogenic factors
Description
Concentrations of angiogenic factors (sFlt-1, sEng, and PlGF)
Time Frame
Between 12-16 weeks, 23-28 weeks, and 33-37 weeks gestation
Title
Concentrations of cholesterol and triglycerides
Description
Concentrations of cholesterol (total, low density lipoprotein, high density lipoprotein) and triglycerides
Time Frame
Between 12-16 weeks, 23-28 weeks, and 33-37 weeks gestation
Title
Proportion of participants with Severe maternal morbidity composite
Description
A composite of severe maternal morbidity of either maternal death, eclampsia, HELLP syndrome, cerebral vascular accident, heart failure, myocardial infarction, acute respiratory distress syndrome requiring mechanical ventilation, disseminated intravascular coagulopathy, pulmonary edema, renal failure, liver rupture, or placental abruption
Time Frame
Randomization through 6 weeks postpartum
Title
Percentage of Fetal or neonatal deaths
Description
Death of the fetus or neonate
Time Frame
randomization through hospital discharge
Title
Birth weight
Description
Birth weight and rate of "small for gestational age" as measured by birth weight: a) < 5th percentile and b) < 10th percentile for gestational age
Time Frame
Birth
Title
NICU/intermediate nursery admission
Description
Admission to the neonatal intensive care unit (NICU) or intermediate nursery
Time Frame
Birth through hospital discharge (through study completion)
Title
NICU/intermediate nursery length of stay
Description
Length of stay in the neonatal intensive care unit (NICU) and/or intermediate nursery
Time Frame
NICU or intermediate nursery admission to NICU or intermediate nursery discharge (through study completion)
Title
Proportion of neonates needing Mechanical ventilation
Description
Mechanical ventilation in the first 72 hours of life and duration
Time Frame
72 hours post birth
Title
Proportion of neonates needing oxygen support
Description
Provision of oxygen support for the neonate and duration
Time Frame
Birth through hospital discharge (through study completion)
Title
Proportion of neonates with Respiratory Distress Syndrome
Description
Respiratory distress syndrome (RDS), defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with an oxygen requirement and confirmed by a chest x-ray
Time Frame
Birth through hospital discharge (through study completion)
Title
Proportion of neonates with Bronchopulmonary Dysplasia
Description
Bronchopulmonary dysplasia (BPD), defined as oxygen requirement at 28 days of life and at 36 weeks corrected gestational age
Time Frame
28 days of life and 36 weeks corrected gestational age
Title
Proportion of neonates with Necrotizing Enterocolitis
Description
Necrotizing enterocolitis (NEC), defined as modified Bell Stage 2 (clinical signs and symptoms with pneumatosis intestinalis on radiographs) or Stage 3 (advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation)
Time Frame
Birth through hospital discharge (through study completion)
Title
Proportion of neonates with Intraventricular Hemorrhage
Description
Intraventricular hemorrhage (IVH) grade III-IV
Time Frame
Birth through hospital discharge (through study completion)
Title
Proportion of neonates with Periventricular leukomalacia (PVL)
Description
Periventricular leukomalacia (PVL), diagnosed by neuroimaging
Time Frame
Diagnosed at Birth through hospital discharge (through study completion)
Title
Proportion of neonates with Retinopathy of prematurity
Description
Retinopathy of prematurity (ROP) stage III or higher
Time Frame
Birth through hospital discharge (through study completion)
Title
Proportion of neonates experiencing sepsis
Description
Neonatal sepsis (within 72 hours and > 72 hours after birth). The diagnosis of sepsis will require the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebral spinal fluid (CSF), or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection.
Time Frame
within 72 hours of birth and greater than 72 hours after birth
Title
Proportion of neonates with Composite Neonatal Outcome
Description
Fetal or neonatal death, RDS, Grade III-IV IVH, PVL, Stage 2 or 3 NEC, BPD, Stage III or higher ROP, or early onset sepsis
Time Frame
Birth through hospital discharge (through study completion)
Title
Proportion of neonates experiencing seizures
Description
Neonatal seizure activity
Time Frame
Birth through hospital discharge (through study completion)
Title
Proportion of neonates with a Congenital anomaly / birth defect
Description
Congenital anomaly or birth defect excluding any conditions that must have been present before randomization
Time Frame
Post randomization through hospital discharge (through study completion)
Title
Neonatal auditory brain stem response (ABR)/Otoacoustic Emissions (OAE)
Description
Neonatal auditory brain stem response (ABR)/Otoacoustic Emissions (OAE)
Time Frame
Delivery through 6 weeks of age
Title
BMI for age at 24 corrected months and 5 years
Description
Body mass index for age at 24 corrected months and 5 years using Centers for Disease Control (CDC) pediatric growth charts
Time Frame
24 months of age and 5 years of age
Title
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
Description
Bayley Certified Scales of Infant Development III Edition scores for cognitive, motor and language abilities at 24 months of age.
Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160. Results can also be expressed as percentile ranks relative to the standardization sample, with a mean and median of 50 and range from 1 to 99
Time Frame
24 months of age
Title
Gross Motor Function at 24 months
Description
Level from the Gross Motor Function Classification System at 24 months of age
Time Frame
24 months of age
Title
Proportion of children with Hearing loss or vision problems at 24 months of age
Description
Hearing loss or vision problems (severe nearsightedness or farsightedness, and eye movement problems) at 24 months of age
Time Frame
24 months of age
Title
Child Behavior Checklist Total Problems Score and Syndrome Scale at 24 months and 5 years
Description
Total problems score and syndrome scale (emotionally reactive, anxious/depressed, somatic complaints, withdrawn, attention problems, aggressive behavior) scores from the Child Behavior Checklist at 24 months and 5 years of age
The CBCL is filled out by the caregiver. Each of the 100 questions indicates a behavior for which the caregiver scores as Not True (0), Sometimes True (1), or Often True (2). The scores for all the questions are then summed and evaluated against the normative data/T-scores. A T-score of less than 60 is considered to be in the normal range. A T-score of 60-63 is a borderline, and a T-score of more than 63 is in the clinical range. Lower scores represent better outcomes.
Time Frame
24 months and 5 years of age
Title
Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)
Description
Overall general conceptual ability score (GCA)and subscale (verbal ability, non-verbal reasoning ability, and spatial ability) scores from the Differential Ability Scales at 5 years of age
Classification:
≥ 130 Very high;120-129 High;110-119 Above average; 90-109 Average; 80-89 Below average;70-79 Low; ≤ 69 Very low
Time Frame
5 years of age
Title
Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite score at 5 years
Description
Assess executive function behaviors in the school and home environments with the BRIEF, a questionnaire developed for parents and teachers of school-age children. Designed to assess the abilities of a broad range of children and adolescents, the BRIEF is useful when working with children who have learning disabilities and attention disorders, traumatic brain injuries, lead exposure, pervasive developmental disorders, depression, and other developmental, neurological, psychiatric, and medical conditions.
Raw scores are converted to T-scores. Higher T-scores indicate greater impairment.
For all BRIEF2 clinical scales and indexes, T-scores from 60 to 64 are considered mildly elevated, and T-scores from 65 to 69 are considered potentially clinically elevated. T-scores at or above 70 are considered clinically elevated.
Time Frame
5 years of age
Title
Vineland Adaptive Behavior Scales - Adaptive Behavior Composite Score at 5 years
Description
Adaptive Behavior Composite score and domain (communication, daily living skills, socialization and motor skills) scores from the Vineland Adaptive Behavior Scale at 5 years of age. Higher scores indicate better functioning.
Domain and ABC Standard Score Ranges High 130 to 140 Moderately High 115 to 129 Adequate 86 to 114 Moderately Low 71 to 85 Low 20 to 70
Time Frame
5 years of age
Title
Visual acuity and strabismus at 5 years
Description
Visual acuity and strabismus from visual assessment at 5 years
Time Frame
5 years of age
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maged Costantine, MD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Monica Longo, MD, PHD
Organizational Affiliation
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Rebecca Clifton, PhD
Organizational Affiliation
The George Washington University Biostatistics Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Victoria Pemberton, RNC, MS, CCRC
Organizational Affiliation
National Heart, Lung, and Blood Institute (NHLBI)
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama - Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Case Western Reserve-Metro Health
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Ohio State University Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Magee Women's Hospital of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Facility Name
University of Texas - Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The dataset will be shared per NIH policy after the completion and publication of the main analyses. The limited access data set will be submitted to NICHD (Data and Specimen Hub - DASH) and NHLBI (Biologic Specimen and Data Repository Information Coordinating Center - BioLINCC).
Citations:
PubMed Identifier
26723196
Citation
Costantine MM, Cleary K, Hebert MF, Ahmed MS, Brown LM, Ren Z, Easterling TR, Haas DM, Haneline LS, Caritis SN, Venkataramanan R, West H, D'Alton M, Hankins G; Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Units Network. Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. Am J Obstet Gynecol. 2016 Jun;214(6):720.e1-720.e17. doi: 10.1016/j.ajog.2015.12.038. Epub 2015 Dec 23.
Results Reference
background
Learn more about this trial
Pravastatin to Prevent Preeclampsia
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