Clinical trial NCT00135707: Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)
Official title: A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia and An Observational Cohort Study to Predict Preeclampsia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preeclampsia
Keywords: Antioxidants
Preeclampsia
Pregnancy
Hypertension
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2005-08-26
Enrollment: 10154
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

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 non-steroidal anti-inflammatory drugs (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 interventional study

Primary outcomes:
measure: Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate
timeFrame: 20 weeks through discharge following delivery
measure: Severe Hypertension
timeFrame: 20 weeks through discharge following delivery
measure: Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels
timeFrame: 20 weeks through discharge following delivery
measure: Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia
timeFrame: 20 weeks through discharge following delivery
measure: Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level
timeFrame: 20 weeks through discharge following delivery
measure: Severe or Mild Pregnancy-associated Hypertension With an Eclamptic Seizure
timeFrame: 20 weeks through discharge following delivery
measure: Severe or Mild Pregnancy-associated Hypertension With an Indicated Preterm Birth Before 32 Weeks of Gestation Owing to Hypertension-related Disorders
timeFrame: 20 weeks through discharge following delivery
measure: 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
timeFrame: 20 weeks through discharge following delivery
measure: Severe or Mild Pregnancy-associated Hypertension With a Fetal Death After 20 Weeks of Gestation or Neonatal Death
timeFrame: 20 weeks through discharge or prior to discharge following delivery admission
Secondary outcomes:
measure: Preeclampsia (Mild, Severe, HELLP Syndrome, Eclampsia)
timeFrame: 20 weeks through discharge following delivery
measure: Pregnancy Associated Hypertension
timeFrame: 20 weeks through discharge following delivery
measure: Medically Indicated Delivery Because of Hypertension
timeFrame: 20 weeks through discharge following delivery
measure: Aspartate Aminotransferase ≥100 U/Liter
timeFrame: 20 weeks through discharge
measure: Creatinine ≥1.5 mg/dl (133 μmol/Liter)
timeFrame: 20 weeks through discharge
measure: Antepartum Bleeding
timeFrame: During pregnancy
measure: Premature Rupture of Membranes
timeFrame: During pregnancy
measure: Placental Abruption
timeFrame: During pregnancy
measure: Cesarean Delivery
timeFrame: Delivery
measure: Maternal Death
timeFrame: Delivery through hospital discharge
measure: Postpartum Pulmonary Edema
timeFrame: After delivery through discharge
measure: Hematocrit ≤24% With Transfusion
timeFrame: Delivery admission to discharge
measure: Maternal Hospital Stay
timeFrame: Delivery through discharge
measure: Gestational Age at Delivery
timeFrame: Delivery
measure: Preterm Birth
timeFrame: Delivery
measure: Fetal or Neonatal Death
timeFrame: During pregnancy or thorugh discharge
measure: Birth Weight
timeFrame: At birth
measure: Small for Gestational Age
timeFrame: At birth
measure: Birth Weight <2500 Grams
timeFrame: At birth
measure: Admission to NICU
timeFrame: Delivery through discharge
measure: Respiratory Distress Syndrome
timeFrame: Delivery through discharge
measure: Intraventricular Hemorrhage, Grade III or IV
timeFrame: Delivery through discharge
measure: Sepsis
timeFrame: Delivery through discharge
measure: Necrotizing Enterocolitis
timeFrame: Delivery through discharge
measure: Retinopathy of Prematurity
timeFrame: Within 1 month of birth
measure: Apgar Score <=3 at 5 Minutes
timeFrame: At birth
measure: Neonatal Hospital Stay
timeFrame: Birth through discharge from hospital
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Case Western University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Magee Womens Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas - Southwest
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: NICHD Project Scientist
name: Menachem Miodovnik, MD
role: STUDY_DIRECTOR
affiliation: George Washington University Biostatistics Center
name: Rebecca Clifton, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh - Magee Womens
name: James M Roberts, MD
role: STUDY_CHAIR
References:
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