Clinical trial NCT00097110: RCT of Antioxidant Therapy to Prevent Preeclampsia in Brazil
Official title: RCT of Antioxidant Therapy to Prevent Preeclampsia in Brazil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preeclampsia
Eclampsia
HELLP Syndrome
Pregnancy
Keywords: Vitamin C
Vitamin E
Preeclampsia
Antioxidants
Global Network
Preterm birth
Low birth weight infants
Brazil
Brasil
Maternal and child health
International
Women's health
Lead sponsor: NICHD Global Network for Women's and Children's Health
Sponsor class: NETWORK
Collaborators: name: Global Network for Women's and Children's Health Research
name: Bill and Melinda Gates Foundation
name: Fogarty International Center of the National Institute of Health
name: National Center for Complementary and Integrative Health (NCCIH)
name: National Institute of Dental and Craniofacial Research (NIDCR)
name: National Cancer Institute (NCI)
name: RTI International
name: University of Cincinnati
name: Universidade Federal de Pernambuco
name: Feculdade de Medicina da Universidade de Sao Paulo - Brasil
name: Faculdade de Medicina de Botucatu, UNESP, Botucatu, Brasil
name: University of Campinas, Brazil
name: Hospital de Clinicas de Porto Alegre
First posted: 2004-11-18
Enrollment: 734
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of preeclampsia
Secondary outcomes:
measure: Severity of preeclampsia
measure: Incidence of gestational hypertension or preeclampsia
measure: Frequency of abruptio placentae
measure: Incidence of preterm birth
measure: Incidence of small for gestational age
measure: Incidence of low birth weight infants
measure: Biomarker level correlation with preeclampsia
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: Federal University of Pernambuco
state: Pernambuco
Study officials:
affiliation: University of Cincinnati
name: Joseph A. Spinnato, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.