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 17 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 CBC.

Condition	Intervention	Phase
Pregnancy	Drug: Vitamins C and E or placebo	Phase III

Further Study Details: 

Primary Outcomes: Severe hypertension (BP> 160/110) or mild hypertension (BP> 140/90) >= 20 weeks gestation in conjunction with one of the following:; SGOT >= 100 U/L; platelet count < 100,000 mm3; serum creatinine >= 1.5 mg/dL; eclamptic seizure; growth restriction (<3rd %tile); indicated preterm birth (<32 weeks) for hypertension related disorders; fetal/neonatal death
Secondary Outcomes: preeclampsia (mild, severe, HELLP, eclampsia); gestational hypertension; serious maternal morbidity; neonatal morbidity and mortality
Expected Total Enrollment:  10000

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 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 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.

Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

RCT inclusion criteria:

• Gestational age 9 -16 weeks
• Singleton pregnancy
• Nulliparous

Observational inclusion criteria:

• Women randomized to the RCT
• Gestational age 9 - 12 wks
• Singleton pregnancy
• Nulliparous

Exclusion criteria RCT and Observational:

• BP > 135/85
• Proteinuria
• History or current use of anti-hypertensive medication or diuretics
• Use of vitamins C > 150 mg and/or E > 75 IU per day
• Pregestational diabetes
• Current pregnancy is a result of in vitro fertilization
• Regular use of platelet active drugs or NSAIDS
• Known fetal abnormalities
• Documented uterine bleeding within a week of screening
• Uterine malformations
• History of medical complications
• Illicit drug or alcohol abuse during current pregnancy
• Intent to deliver elsewhere
• Participating in another invention study

Please refer to this study by ClinicalTrials.gov identifier  NCT00135707

James M. Roberts, MD      412-641-1426    RSIJMR@mwri.magee.edu

Alabama
      University of Alabama - Birmingham, Birmingham,  Alabama,  35233,  United States; Recruiting
Illinois
      Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
Michigan
      Wayne State University, Detroit,  Michigan,  48201,  United States; Recruiting
New York
      Columbia University, New York,  New York,  10032,  United States; Recruiting
North Carolina
      Wake Forest University School of Medicine, Winston Salem,  North Carolina,  27157,  United States; Recruiting
      University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599,  United States; Recruiting
Ohio
      Ohio State University, Columbus,  Ohio,  43210,  United States; Recruiting
      Case Western University, Cleveland,  Ohio,  44109,  United States; Recruiting
Pennsylvania
      University of Pittsburgh Magee Womens Hospital, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
      Drexel University, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting
Rhode Island
      Brown University, Providence,  Rhode Island,  02905,  United States; Recruiting
Texas
      University of Texas - Southwest, Dallas,  Texas,  75235,  United States; Recruiting
      University of Texas - Houston, Houston,  Texas,  77030,  United States; Recruiting
Utah
      University of Utah Medical Center, Salt Lake City,  Utah,  84132,  United States; Recruiting

Study chairs or principal investigators

Catherine Spong, MD,  Study Director,  National Institute of Child Health and Human Development (NICHD)   
Elizabeth A Thom, Ph.D.,  Principal Investigator,  George Washington University Biostatistics Center   

Study ID Numbers:  HD36801-CAPPS; IRB#
Last Updated:  August 25, 2005
Record first received:  August 24, 2005
ClinicalTrials.gov Identifier:  NCT00135707
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-30