RCT of Antioxidant Therapy to Prevent Preeclampsia in Brazil

The perinatal morbidity and mortality rates for Brazil are five to ten-fold higher than those reported for upper income countries. This study tests the likelihood that the joint administration of antioxidants vitamin C (1000 mg) and vitamin E (400 IU) will reduce the incidence of preeclampsia among chronically hypertensive pregnant patients and patients with a past history of preeclampsia/eclampsia.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Eclampsia; Preeclampsia; HELLP Syndrome
• Intervention / Treatment: Drug: Vitamin C and E

Detailed Description

The maternal, perinatal and neonatal morbidity and mortality rates for Brazil are five to ten-fold higher than those reported for upper income countries. In Sao Paulo, 22 percent of maternal deaths are attributable to hypertensive complications of pregnancy, which ranks as the number one cause of maternal death. Recent advances in the understanding of the pathophysiology of preeclampsia suggest the possibility of antioxidant therapy for the prevention of preeclampsia. The primary hypothesis is that the joint administration of the antioxidants vitamin C (1000 mg) and vitamin E (400 IU) will reduce the incidence of preeclampsia among chronically hypertensive pregnant patients and patients with a past history of preeclampsia/eclampsia. Secondary outcomes include severity of preeclampsia; incidence of gestational hypertension; incidence of premature rupture of the membranes; incidence of preterm birth; incidence of low birth weight infants; biomarker level correlation with preeclampsia.

Study sites are high-risk obstetrical clinics in the Brazilian cities of Recife, Botucatu, Campinas, and Porto Alegre. The sample size was based on an estimated risk of preeclampsia/eclampsia of 21-25% in the control group. The study hypothesizes a 40% absolute reduction of risk of preeclampsia; early treatment withdrawal of 3%; withdrawal of consent or loss to follow-up of 10%; calculated at a 0.05 significance level with 80% power. Seven hundred thirty-four obstetric patients with chronic hypertension or preeclampsia in the prior pregnancy presenting for care between 12 weeks and 19 weeks', 6 days gestation will be randomized to a double-blinded placebo controlled trial to receive a daily dose of either vitamin E (400 International Units) and vitamin C (1000 mg) or placebo from the time of enrollment to delivery. The use of MEMS caps enables researchers to accurately track compliance.

• Study Type: Interventional
• Enrollment: 734
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Pernambuco
    • Recife, Pernambuco, Brazil
      • Federal University of Pernambuco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Gestational age between 12 weeks and 19 weeks, 6 days, inclusive
• Chronic hypertension
• History of preeclampsia/eclampsia
• Attendance at a participating hospital (Recife, Botucatu, Campinas and Porto Alegre, Brazil)

Exclusion Criteria:

• Planned delivery elsewhere.
• Multifetal gestation.
• Allergy to vitamin C or vitamin E.
• Requirement for aspirin or anticoagulant medication.
• Proteinuria ≥ 2+ on dipstick urine test; or proteinuria = 1+ on dipstick and ≥ 300 mg/24 hours.
• Pre-pregnancy diabetes mellitus.
• Known fetal anomaly incompatible with life.
• Prior participation in the study.
• Unwillingness to take the study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Incidence of preeclampsia

Secondary Outcome Measures

Outcome Measure
Severity of preeclampsia
Incidence of gestational hypertension or preeclampsia
Frequency of abruptio placentae
Incidence of preterm birth
Incidence of small for gestational age
Incidence of low birth weight infants
Biomarker level correlation with preeclampsia

Collaborators and Investigators

• Sponsor: NICHD Global Network for Women's and Children's Health
• Collaborators: National Cancer Institute (NCI); Hospital de Clinicas de Porto Alegre; National Institute of Dental and Craniofacial Research (NIDCR); Bill and Melinda Gates Foundation; National Center for Complementary and Integrative Health (NCCIH); University of Campinas, Brazil; Universidade Federal de Pernambuco; University of Cincinnati; Fogarty International Center of the National Institute of Health; RTI International; Global Network for Women's and Children's Health Research; Faculdade de Medicina de Botucatu, UNESP, Botucatu, Brasil; Feculdade de Medicina da Universidade de Sao Paulo - Brasil
• Investigators: Principal Investigator: Joseph A. Spinnato, M.D., University of Cincinnati

Publications and helpful links

General Publications

• Spinnato JA 2nd, Freire S, Pinto e Silva JL, Rudge MV, Martins-Costa S, Koch MA, Goco N, Santos Cde B, Cecatti JG, Costa R, Ramos JG, Moss N, Sibai BM. Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis. Am J Obstet Gynecol. 2008 Oct;199(4):433.e1-8. doi: 10.1016/j.ajog.2008.07.011.
• Spinnato JA 2nd, Freire S, Pinto E Silva JL, Cunha Rudge MV, Martins-Costa S, Koch MA, Goco N, Santos Cde B, Cecatti JG, Costa R, Ramos JG, Moss N, Sibai BM. Antioxidant therapy to prevent preeclampsia: a randomized controlled trial. Obstet Gynecol. 2007 Dec;110(6):1311-8. doi: 10.1097/01.AOG.0000289576.43441.1f.

Helpful Links

• Global Network for Women's and Children's Health Research
• RTI International

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Study Completion (ACTUAL): December 1, 2006

Study Registration Dates

• First Submitted: November 17, 2004
• First Submitted That Met QC Criteria: November 17, 2004
• First Posted (ESTIMATE): November 18, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2013
• Last Update Submitted That Met QC Criteria: November 22, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Antioxidants; Vitamin E; Vitamin C; International; Maternal and child health; Preeclampsia; Brazil; Preterm birth; Global Network; Low birth weight infants; Women's health; Brasil
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia; HELLP Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: GN 05; U01HD040565 (NIH)