A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia and An Observational Cohort Study to Predict Preeclampsia
Overview
- Phase
- Phase 3
- Intervention
- Dietary Supplement/Vitamins
- Conditions
- Preeclampsia
- Sponsor
- The George Washington University Biostatistics Center
- Enrollment
- 10154
- Locations
- 16
- Primary Endpoint
- Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
Preeclampsia is one of the most common complications of pregnancy and is characterized by high blood pressure and protein in the urine. This can cause problems in the second half of pregnancy for both the mother and fetus. This study of preeclampsia consists of two parts: 1) a randomized, placebo controlled, multicenter clinical trial of 10,000 low-risk nulliparous women between 9 and 16 weeks gestation and 2) an observational, cohort study of 4,000 patients between 9 and 12 weeks gestation who are also enrolled in the trial.
Subjects in both parts will receive either 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo daily. The purpose of the randomized, clinical trial is to find out if high doses of vitamin C and E will reduce the risk of preeclampsia and other problems associated with the disease. The study will also evaluate the safety of antioxidant therapy for mother and infant. Patients will be seen monthly to receive their supply of study drug, to have weight and blood pressure recorded, to have urine protein measured, and to assess any side effects. At two visits, blood and urine will be collected.
The observational, cohort study will prospectively measure potential biochemical and biophysical markers that might predict preeclampsia. These patients will have additional procedures including uterine artery Doppler and blood drawn for a complete blood count (CBC).
Detailed Description
A Randomized, Clinical Trial of Antioxidants to Prevent Preeclampsia: Preeclampsia is the leading cause of maternal morbidity, as well as perinatal morbidity and mortality. Once the diagnosis has been established, therapy other than delivery has not been successful except to prolong pregnancy minimally (at some risk to mother and infant). Prevention efforts to reduce or eliminate preeclampsia are directed at the pathophysiology of the disorder prior to clinically evident preeclampsia and before irreversible changes have occurred. This double-masked, placebo-controlled trial of 10,000 subjects is designed to evaluate the effects of antioxidant therapy in preventing serious complications associated with pregnancy-related hypertension in low risk, nulliparous women who begin treatment at 9-16 weeks gestation. The hypothesis being tested is that antioxidant therapy initiated prior to 16 weeks gestation will reduce the frequency of serious maternal and infant complications associated with pregnancy-related hypertension. After randomization, subjects will receive either 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo daily. They will be seen for monthly pill counts and to assess side effects, weight, blood pressure, and urine for protein. Blood and urine are collected at 24 and 32 weeks' gestation. An Observational Cohort Study to Predict Preeclampsia: A prospective, cohort study has been designed to complement the randomized, controlled, trial (RCT) and will test various biochemical and biophysical markers for ability to predict preeclampsia in 4,000 of the women who are enrolled in the RCT and are between 9 and 12 weeks gestation. These subjects will have additional procedures including a CBC and uterine artery Doppler.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Gestational age 9 -16 weeks
- •Singleton pregnancy
- •Nulliparous
- •Observational Inclusion Criteria:
- •Women randomized to the RCT
- •Gestational age 9 - 12 wks
- •Exclusion Criteria RCT and Observational:
- •BP \>= 135/85
- •Proteinuria
- •History or current use of anti-hypertensive medication or diuretics
Exclusion Criteria
- Not provided
Arms & Interventions
Dietary Supplement/Vitamins
1000mg of Vitamin C and 400IU of Vitamin E per capsule, twice daily between randomization (at 9 to 16 weeks) up to delivery.
Intervention: Dietary Supplement/Vitamins
Placebo for Vitamin C and Vitamin E
Placebo capsules consisting of Mineral Oil, Hydrogenated Vegetable Oil, Lecithin, Yellow wax, Soft Gelatin Shell, twice daily between randomization (at 9 to 16 weks) up to delivery.
Intervention: Placebo for Vitamin C and Vitamin E
Outcomes
Primary Outcomes
Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels
Time Frame: 20 weeks through discharge following delivery
Elevated liver enzyme levels are specified as an aspartate aminotransferase level of \>= 100 U per liter. Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia
Time Frame: 20 weeks through discharge following delivery
Thrombocytopenia defined as a platelet count of \<100,000 per cubic millimeter. Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level
Time Frame: 20 weeks through discharge following delivery
Elevated serum creatinine defined as ≥1.5 mg per deciliter or 132.6 μmol per liter. Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With an Indicated Preterm Birth Before 32 Weeks of Gestation Owing to Hypertension-related Disorders
Time Frame: 20 weeks through discharge following delivery
Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate
Time Frame: 20 weeks through discharge following delivery
Severe hypertension (blood pressure \[BP\]\>= 160/110) or mild hypertension (BP\>= 140/90) \>= 20 weeks gestation in conjunction with one of the following: elevated liver enzymes, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, an indicated preterm birth before 32 weeks of gestation owing to hypertension-related disorders, a fetus that was small for gestational age (below 3rd percentile) adjusted for sex and race or ethnic group, fetal death after 20 weeks of gestation, or neonatal death
Severe or Mild Pregnancy-associated Hypertension With an Eclamptic Seizure
Time Frame: 20 weeks through discharge following delivery
Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe Hypertension
Time Frame: 20 weeks through discharge following delivery
Included here are women who had severe hypertension only and those who had severe hypertension with elevated liver enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or fetal death after 20 weeks of gestation, or neonatal death.
Severe or Mild Pregnancy-associated Hypertension With a Fetal Death After 20 Weeks of Gestation or Neonatal Death
Time Frame: 20 weeks through discharge or prior to discharge following delivery admission
Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With a Fetus That Was Small for Gestational Age (Below the 3rd Percentile) Adjusted for Sex and Race or Ethnic Group
Time Frame: 20 weeks through discharge following delivery
Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Secondary Outcomes
- Retinopathy of Prematurity(Within 1 month of birth)
- Preeclampsia (Mild, Severe, HELLP Syndrome, Eclampsia)(20 weeks through discharge following delivery)
- Pregnancy Associated Hypertension(20 weeks through discharge following delivery)
- Medically Indicated Delivery Because of Hypertension(20 weeks through discharge following delivery)
- Cesarean Delivery(Delivery)
- Creatinine ≥1.5 mg/dl (133 μmol/Liter)(20 weeks through discharge)
- Placental Abruption(During pregnancy)
- Hematocrit ≤24% With Transfusion(Delivery admission to discharge)
- Preterm Birth(Delivery)
- Respiratory Distress Syndrome(Delivery through discharge)
- Sepsis(Delivery through discharge)
- Apgar Score <=3 at 5 Minutes(At birth)
- Maternal Hospital Stay(Delivery through discharge)
- Birth Weight(At birth)
- Admission to NICU(Delivery through discharge)
- Necrotizing Enterocolitis(Delivery through discharge)
- Aspartate Aminotransferase ≥100 U/Liter(20 weeks through discharge)
- Premature Rupture of Membranes(During pregnancy)
- Gestational Age at Delivery(Delivery)
- Fetal or Neonatal Death(During pregnancy or thorugh discharge)
- Antepartum Bleeding(During pregnancy)
- Maternal Death(Delivery through hospital discharge)
- Postpartum Pulmonary Edema(After delivery through discharge)
- Small for Gestational Age(At birth)
- Birth Weight <2500 Grams(At birth)
- Intraventricular Hemorrhage, Grade III or IV(Delivery through discharge)
- Neonatal Hospital Stay(Birth through discharge from hospital)