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

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ClinicalTrials.gov Identifier: NCT00135707
Recruitment Status : Completed
First Posted : August 26, 2005
Results First Posted : November 20, 2018
Last Update Posted : November 20, 2018
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

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).


Condition or disease Intervention/treatment Phase
Preeclampsia Drug: Dietary Supplement/Vitamins Drug: Placebo for Vitamin C and Vitamin E Phase 3

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 : Interventional  (Clinical Trial)
Actual Enrollment : 10154 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia and An Observational Cohort Study to Predict Preeclampsia
Study Start Date : June 2003
Actual Primary Completion Date : October 2008
Actual Study Completion Date : January 2009


Arm Intervention/treatment
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.
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

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.
Drug: Placebo for Vitamin C and Vitamin E
Placebo two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery.




Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.


Secondary Outcome Measures :
  1. 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.

  2. Pregnancy Associated Hypertension [ Time Frame: 20 weeks through discharge following delivery ]
  3. Medically Indicated Delivery Because of Hypertension [ Time Frame: 20 weeks through discharge following delivery ]
  4. Aspartate Aminotransferase ≥100 U/Liter [ Time Frame: 20 weeks through discharge ]
  5. Creatinine ≥1.5 mg/dl (133 μmol/Liter) [ Time Frame: 20 weeks through discharge ]
  6. Antepartum Bleeding [ Time Frame: During pregnancy ]
  7. Premature Rupture of Membranes [ Time Frame: During pregnancy ]
  8. Placental Abruption [ Time Frame: During pregnancy ]
  9. Cesarean Delivery [ Time Frame: Delivery ]
  10. Maternal Death [ Time Frame: Delivery through hospital discharge ]
  11. Postpartum Pulmonary Edema [ Time Frame: After delivery through discharge ]
  12. Hematocrit ≤24% With Transfusion [ Time Frame: Delivery admission to discharge ]
  13. Maternal Hospital Stay [ Time Frame: Delivery through discharge ]
  14. Gestational Age at Delivery [ Time Frame: Delivery ]
  15. Preterm Birth [ Time Frame: Delivery ]
  16. Fetal or Neonatal Death [ Time Frame: During pregnancy or thorugh discharge ]
  17. Birth Weight [ Time Frame: At birth ]
  18. 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)

  19. Birth Weight <2500 Grams [ Time Frame: At birth ]
  20. Admission to NICU [ Time Frame: Delivery through discharge ]
    NICU denotes neonatal intensive care unit.

  21. Respiratory Distress Syndrome [ Time Frame: Delivery through discharge ]
  22. Intraventricular Hemorrhage, Grade III or IV [ Time Frame: Delivery through discharge ]
  23. Sepsis [ Time Frame: Delivery through discharge ]
  24. Necrotizing Enterocolitis [ Time Frame: Delivery through discharge ]
  25. Retinopathy of Prematurity [ Time Frame: Within 1 month of birth ]
  26. Apgar Score <=3 at 5 Minutes [ Time Frame: At birth ]
  27. Neonatal Hospital Stay [ Time Frame: Birth through discharge from hospital ]


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00135707


Locations
United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States, 35233
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Case Western University
Cleveland, Ohio, United States, 44109
Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health and Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Drexel University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas - Southwest
Dallas, Texas, United States, 75235
University of Texas Medical Branch
Galveston, Texas, United States, 77555
University of Texas - Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
The George Washington University Biostatistics Center
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Study Director: Uma Reddy, MD, MPH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Elizabeth A Thom, Ph.D. George Washington University Biostatistics Center
Study Chair: James M Roberts, MD University of Pittsburgh - Magee Womens

Additional Information:
Publications of Results:
Other Publications:

Responsible Party: The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier: NCT00135707     History of Changes
Other Study ID Numbers: 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 )
First Posted: August 26, 2005    Key Record Dates
Results First Posted: November 20, 2018
Last Update Posted: November 20, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
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.

Keywords provided by The George Washington University Biostatistics Center:
Antioxidants
Preeclampsia
Pregnancy
Hypertension

Additional relevant MeSH terms:
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications
Vitamins
Ascorbic Acid
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Antioxidants
Micronutrients
Growth Substances
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Protective Agents