Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS) (CAPPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00135707
Recruitment Status : Completed
First Posted : August 26, 2005
Results First Posted : November 20, 2018
Last Update Posted : February 21, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center

Tracking Information
First Submitted Date  ICMJE August 24, 2005
First Posted Date  ICMJE August 26, 2005
Results First Submitted Date  ICMJE November 1, 2012
Results First Posted Date  ICMJE November 20, 2018
Last Update Posted Date February 21, 2019
Study Start Date  ICMJE June 2003
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
  • Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate [ Time Frame: 20 weeks through discharge following delivery ]
    Severe hypertension (blood pressure [BP]>= 160/110) or mild hypertension (BP>= 140/90) >= 20 weeks gestation in conjunction with one of the following: elevated liver enzymes, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, an indicated preterm birth before 32 weeks of gestation owing to hypertension-related disorders, a fetus that was small for gestational age (below 3rd percentile) adjusted for sex and race or ethnic group, fetal death after 20 weeks of gestation, or neonatal death
  • Severe Hypertension [ Time Frame: 20 weeks through discharge following delivery ]
    Included here are women who had severe hypertension only and those who had severe hypertension with elevated liver enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or fetal death after 20 weeks of gestation, or neonatal death.
  • Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels [ Time Frame: 20 weeks through discharge following delivery ]
    Elevated liver enzyme levels are specified as an aspartate aminotransferase level of >= 100 U per liter. Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
  • Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia [ Time Frame: 20 weeks through discharge following delivery ]
    Thrombocytopenia defined as a platelet count of <100,000 per cubic millimeter. Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
  • Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level [ Time Frame: 20 weeks through discharge following delivery ]
    Elevated serum creatinine defined as ≥1.5 mg per deciliter or 132.6 μmol per liter. Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
  • Severe or Mild Pregnancy-associated Hypertension With an Eclamptic Seizure [ Time Frame: 20 weeks through discharge following delivery ]
    Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
  • Severe or Mild Pregnancy-associated Hypertension With an Indicated Preterm Birth Before 32 Weeks of Gestation Owing to Hypertension-related Disorders [ Time Frame: 20 weeks through discharge following delivery ]
    Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
  • 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 [ Time Frame: 20 weeks through discharge following delivery ]
    Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
  • Severe or Mild Pregnancy-associated Hypertension With a Fetal Death After 20 Weeks of Gestation or Neonatal Death [ Time Frame: 20 weeks through discharge or prior to discharge following delivery admission ]
    Women who met more than one component of the primary outcome were counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Original Primary Outcome Measures  ICMJE
 (submitted: August 24, 2005)
  • 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
Change History Complete list of historical versions of study NCT00135707 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
  • Preeclampsia (Mild, Severe, HELLP Syndrome, Eclampsia) [ Time Frame: 20 weeks through discharge following delivery ]
    HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.
  • Pregnancy Associated Hypertension [ Time Frame: 20 weeks through discharge following delivery ]
  • Medically Indicated Delivery Because of Hypertension [ Time Frame: 20 weeks through discharge following delivery ]
  • Aspartate Aminotransferase ≥100 U/Liter [ Time Frame: 20 weeks through discharge ]
  • Creatinine ≥1.5 mg/dl (133 μmol/Liter) [ Time Frame: 20 weeks through discharge ]
  • Antepartum Bleeding [ Time Frame: During pregnancy ]
  • Premature Rupture of Membranes [ Time Frame: During pregnancy ]
  • Placental Abruption [ Time Frame: During pregnancy ]
  • Cesarean Delivery [ Time Frame: Delivery ]
  • Maternal Death [ Time Frame: Delivery through hospital discharge ]
  • Postpartum Pulmonary Edema [ Time Frame: After delivery through discharge ]
  • Hematocrit ≤24% With Transfusion [ Time Frame: Delivery admission to discharge ]
  • Maternal Hospital Stay [ Time Frame: Delivery through discharge ]
  • Gestational Age at Delivery [ Time Frame: Delivery ]
  • Preterm Birth [ Time Frame: Delivery ]
  • Fetal or Neonatal Death [ Time Frame: During pregnancy or thorugh discharge ]
  • Birth Weight [ Time Frame: At birth ]
  • Small for Gestational Age [ Time Frame: At birth ]
    A baby whose birth weight is less than the 3rd percentile is considered to be small for gestational age (adjusted for sex and race or ethnic group)
  • Birth Weight <2500 Grams [ Time Frame: At birth ]
  • Admission to NICU [ Time Frame: Delivery through discharge ]
    NICU denotes neonatal intensive care unit.
  • Respiratory Distress Syndrome [ Time Frame: Delivery through discharge ]
  • Intraventricular Hemorrhage, Grade III or IV [ Time Frame: Delivery through discharge ]
  • Sepsis [ Time Frame: Delivery through discharge ]
  • Necrotizing Enterocolitis [ Time Frame: Delivery through discharge ]
  • Retinopathy of Prematurity [ Time Frame: Within 1 month of birth ]
  • Apgar Score <=3 at 5 Minutes [ Time Frame: At birth ]
  • Neonatal Hospital Stay [ Time Frame: Birth through discharge from hospital ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2005)
  • preeclampsia (mild, severe, HELLP, eclampsia)
  • gestational hypertension
  • serious maternal morbidity
  • neonatal morbidity and mortality
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)
Official Title  ICMJE A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia and An Observational Cohort Study to Predict Preeclampsia
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Preeclampsia
Intervention  ICMJE
  • Drug: Dietary Supplement/Vitamins
    Vitamin C (1000 mg) and Vitamin E (400 IU) per capsule, two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery.
    Other Name: Ascorbic Acid and d-alpha-Tocopheryl Acetate
  • Drug: Placebo for Vitamin C and Vitamin E
    Placebo two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery.
Study Arms  ICMJE
  • Experimental: Dietary Supplement/Vitamins
    1000mg of Vitamin C and 400IU of Vitamin E per capsule, twice daily between randomization (at 9 to 16 weeks) up to delivery.
    Intervention: Drug: Dietary Supplement/Vitamins
  • Placebo Comparator: Placebo for Vitamin C and Vitamin E
    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.
    Intervention: Drug: Placebo for Vitamin C and Vitamin E
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 20, 2008)
10154
Original Enrollment  ICMJE
 (submitted: August 24, 2005)
10000
Actual Study Completion Date  ICMJE January 2009
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00135707
Other Study ID Numbers  ICMJE HD36801-CAPPS
U10HD021410 ( U.S. NIH Grant/Contract )
U10HD027869 ( U.S. NIH Grant/Contract )
U10HD027917 ( U.S. NIH Grant/Contract )
U10HD027860 ( U.S. NIH Grant/Contract )
U10HD027915 ( U.S. NIH Grant/Contract )
U10HD034116 ( U.S. NIH Grant/Contract )
U10HD034208 ( U.S. NIH Grant/Contract )
U10HD034136 ( U.S. NIH Grant/Contract )
U10HD040500 ( U.S. NIH Grant/Contract )
U10HD040485 ( U.S. NIH Grant/Contract )
U10HD040544 ( U.S. NIH Grant/Contract )
U10HD040545 ( U.S. NIH Grant/Contract )
U10HD040560 ( U.S. NIH Grant/Contract )
U10HD040512 ( U.S. NIH Grant/Contract )
U01HD036801 ( U.S. NIH Grant/Contract )
U10HD053097 ( U.S. NIH Grant/Contract )
U10HD053118 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data will be shared after completion of the trial an publication of the main analyses per NIH Policy. Requests should be emailed to mfmudatasets@bsc.gwu.edu.
Responsible Party The George Washington University Biostatistics Center
Study Sponsor  ICMJE The George Washington University Biostatistics Center
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Study Director: Menachem Miodovnik, MD NICHD Project Scientist
Principal Investigator: Rebecca Clifton, Ph.D. George Washington University Biostatistics Center
Study Chair: James M Roberts, MD University of Pittsburgh - Magee Womens
PRS Account The George Washington University Biostatistics Center
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP