Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)

The George Washington University Biostatistics Center

Status and phase: Completed; Phase 3

Conditions: Preeclampsia

Treatments: Drug: Placebo for Vitamin C and Vitamin E; Drug: Dietary Supplement/Vitamins

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00135707

U10HD053097 (U.S. NIH Grant/Contract)

U10HD034116 (U.S. NIH Grant/Contract)

U10HD040544 (U.S. NIH Grant/Contract)

U10HD027860 (U.S. NIH Grant/Contract)

U10HD053118 (U.S. NIH Grant/Contract)

U10HD040545 (U.S. NIH Grant/Contract)

U10HD034136 (U.S. NIH Grant/Contract)

U10HD040500 (U.S. NIH Grant/Contract)

U01HD036801 (U.S. NIH Grant/Contract)

U10HD027915 (U.S. NIH Grant/Contract)

U10HD027917 (U.S. NIH Grant/Contract)

U10HD027869 (U.S. NIH Grant/Contract)

U10HD034208 (U.S. NIH Grant/Contract)

HD36801-CAPPS

U10HD040560 (U.S. NIH Grant/Contract)

U10HD040512 (U.S. NIH Grant/Contract)

U10HD040485 (U.S. NIH Grant/Contract)

U10HD021410 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 10,154 patients

Sex: Female

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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10,154 participants in 2 patient groups, including a placebo group

Dietary Supplement/Vitamins

Experimental group

Description:

1000mg of Vitamin C and 400IU of Vitamin E per capsule, twice daily between randomization (at 9 to 16 weeks) up to delivery.

Treatment:

Drug: Dietary Supplement/Vitamins

Placebo for Vitamin C and Vitamin E

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo for Vitamin C and Vitamin E