Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)

NCT00135707 | Completed Phase 3 Results DMC

• 18 other identifiers: HD36801-CAPPSU10HD021410U10HD027869U10HD027917U10HD027860U10HD027915U10HD034116U10HD034208U10HD034136U10HD040500U10HD040485U10HD040544U10HD040545U10HD040560U10HD040512U01HD036801U10HD053097U10HD053118
• Study Type: interventional
• Target: 10,154
• Locations: 1 country
• Sites: 16

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).

Conditions

Preeclampsia

Keywords

Antioxidants; Preeclampsia; Pregnancy; Hypertension

Outcome Measures

Primary Outcomes (9)

• Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate

  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

  20 weeks through discharge following delivery

• Severe Hypertension

  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.

  20 weeks through discharge following delivery

• Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels

  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.

  20 weeks through discharge following delivery

• Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia

  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.

  20 weeks through discharge following delivery

• Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level

  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.

  20 weeks through discharge following delivery

• Severe or Mild Pregnancy-associated Hypertension With an Eclamptic Seizure

  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.

  20 weeks through discharge following delivery

• Severe or Mild Pregnancy-associated Hypertension With an Indicated Preterm Birth Before 32 Weeks of Gestation Owing to Hypertension-related Disorders

  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.

  20 weeks through discharge following delivery

• 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

  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.

  20 weeks through discharge following delivery

• Severe or Mild Pregnancy-associated Hypertension With a Fetal Death After 20 Weeks of Gestation or Neonatal Death

  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.

  20 weeks through discharge or prior to discharge following delivery admission

Secondary Outcomes (27)

• Preeclampsia (Mild, Severe, HELLP Syndrome, Eclampsia)

  20 weeks through discharge following delivery

• Pregnancy Associated Hypertension

  20 weeks through discharge following delivery

• Medically Indicated Delivery Because of Hypertension

  20 weeks through discharge following delivery

• Aspartate Aminotransferase ≥100 U/Liter

  20 weeks through discharge

• Creatinine ≥1.5 mg/dl (133 μmol/Liter)

  20 weeks through discharge

Study Arms (2)

Dietary Supplement/Vitamins

EXPERIMENTAL

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

Placebo for Vitamin C and Vitamin E

PLACEBO COMPARATOR

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

Interventions

Dietary Supplement/Vitamins DRUG

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

Also known as: Ascorbic Acid and d-alpha-Tocopheryl Acetate

Dietary Supplement/Vitamins

Placebo for Vitamin C and Vitamin E DRUG

Placebo two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery.

Placebo for Vitamin C and Vitamin E

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gestational age 9 -16 weeks
• Singleton pregnancy
• Nulliparous
• Women randomized to the RCT
• Gestational age 9 - 12 wks

You may not qualify if:

• 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

Sponsors & Collaborators

• The George Washington University Biostatistics Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (16)

University of Alabama - Birmingham

Birmingham, Alabama, 35233, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Case Western University

Cleveland, Ohio, 44109, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Drexel University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown University

Providence, Rhode Island, 02905, United States

Location

University of Texas - Southwest

Dallas, Texas, 75235, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Texas - Houston

Houston, Texas, 77030, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

Related Publications (18)

• Hauth JC, Clifton RG, Roberts JM, Myatt L, Spong CY, Leveno KJ, Varner MW, Wapner RJ, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Samuels P, Sciscione A, Tolosa JE, Saade G, Sorokin Y, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Maternal insulin resistance and preeclampsia. Am J Obstet Gynecol. 2011 Apr;204(4):327.e1-6. doi: 10.1016/j.ajog.2011.02.024.

  PMID: 21458622 BACKGROUND

• Carreno CA, Clifton RG, Hauth JC, Myatt L, Roberts JM, Spong CY, Varner MW, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Sciscione A, Tolosa JE, Saade GR, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Excessive early gestational weight gain and risk of gestational diabetes mellitus in nulliparous women. Obstet Gynecol. 2012 Jun;119(6):1227-33. doi: 10.1097/AOG.0b013e318256cf1a. Erratum In: Obstet Gynecol. 2012 Sep;120(3):710. Saade, George R [added].

  PMID: 22617588 BACKGROUND

• Myatt L, Clifton RG, Roberts JM, Spong CY, Hauth JC, Varner MW, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Iams JD, Sciscione A, Harper M, Tolosa JE, Saade G, Sorokin Y, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. First-trimester prediction of preeclampsia in nulliparous women at low risk. Obstet Gynecol. 2012 Jun;119(6):1234-42. doi: 10.1097/AOG.0b013e3182571669.

  PMID: 22617589 BACKGROUND

• Myatt L, Clifton RG, Roberts JM, Spong CY, Hauth JC, Varner MW, Wapner RJ, Thorp JM Jr, Mercer BM, Grobman WA, Ramin SM, Carpenter MW, Samuels P, Sciscione A, Harper M, Tolosa JE, Saade G, Sorokin Y, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). The utility of uterine artery Doppler velocimetry in prediction of preeclampsia in a low-risk population. Obstet Gynecol. 2012 Oct;120(4):815-22. doi: 10.1097/AOG.0b013e31826af7fb.

  PMID: 22996099 BACKGROUND

• Weissgerber TL, Gandley RE, McGee PL, Spong CY, Myatt L, Leveno KJ, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Samuels P, Sciscione A, Harper M, Tolosa JE, Saade G, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population. PLoS One. 2013;8(4):e60479. doi: 10.1371/journal.pone.0060479. Epub 2013 Apr 3.

  PMID: 23573260 BACKGROUND

• Johnson J, Clifton RG, Roberts JM, Myatt L, Hauth JC, Spong CY, Varner MW, Wapner RJ, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Samuels P, Sciscione A, Harper M, Tolosa JE, Saade G, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*. Pregnancy outcomes with weight gain above or below the 2009 Institute of Medicine guidelines. Obstet Gynecol. 2013 May;121(5):969-975. doi: 10.1097/AOG.0b013e31828aea03.

  PMID: 23635732 BACKGROUND

• Myatt L, Clifton RG, Roberts JM, Spong CY, Wapner RJ, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Sciscione A, Tolosa JE, Saade G, Sorokin Y, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population? BJOG. 2013 Sep;120(10):1183-91. doi: 10.1111/1471-0528.12128. Epub 2013 Jan 18.

  PMID: 23331974 BACKGROUND

• Makhlouf MA, Clifton RG, Roberts JM, Myatt L, Hauth JC, Leveno KJ, Varner MW, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Iams JD, Sciscione A, Tolosa JE, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network. Adverse pregnancy outcomes among women with prior spontaneous or induced abortions. Am J Perinatol. 2014 Oct;31(9):765-72. doi: 10.1055/s-0033-1358771. Epub 2013 Dec 17.

  PMID: 24347257 BACKGROUND

• Cantu J, Clifton RG, Roberts JM, Leveno KJ, Myatt L, Reddy UM, Varner MW, Wapner RJ, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Samuels P, Sciscione A, Saade G, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Laboratory abnormalities in pregnancy-associated hypertension: frequency and association with pregnancy outcomes. Obstet Gynecol. 2014 Nov;124(5):933-940. doi: 10.1097/AOG.0000000000000509.

  PMID: 25437721 BACKGROUND

• Weissgerber TL, McGee PL, Myatt L, Hauth JC, Varner MW, Wapner RJ, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Samuels P, Sciscione AC, Harper M, Saade G, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Haptoglobin phenotype and abnormal uterine artery Doppler in a racially diverse cohort. J Matern Fetal Neonatal Med. 2014 Nov;27(17):1728-33. doi: 10.3109/14767058.2013.876622. Epub 2014 Jan 13.

  PMID: 24345080 BACKGROUND

• Abramovici A, Gandley RE, Clifton RG, Leveno KJ, Myatt L, Wapner RJ, Thorp JM Jr, Mercer BM, Peaceman AM, Samuels P, Sciscione A, Harper M, Saade G, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network. Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis. BJOG. 2015 Dec;122(13):1740-7. doi: 10.1111/1471-0528.13201. Epub 2014 Dec 17.

  PMID: 25516497 BACKGROUND

• Basraon SK, Mele L, Myatt L, Roberts JM, Hauth JC, Leveno KJ, Varner MW, Wapner RJ, Thorp JM Jr, Peaceman AM, Ramin SM, Sciscione A, Tolosa JE, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Relationship of Early Pregnancy Waist-to-Hip Ratio versus Body Mass Index with Gestational Diabetes Mellitus and Insulin Resistance. Am J Perinatol. 2016 Jan;33(1):114-21. doi: 10.1055/s-0035-1562928. Epub 2015 Sep 9.

  PMID: 26352680 BACKGROUND

• McDonnold M, Mele LM, Myatt L, Hauth JC, Leveno KJ, Reddy UM, Mercer BM; Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units (MFMU) Network. Waist-to-Hip Ratio versus Body Mass Index as Predictor of Obesity-Related Pregnancy Outcomes. Am J Perinatol. 2016 May;33(6):618-24. doi: 10.1055/s-0035-1569986. Epub 2016 Jan 20.

  PMID: 26788786 BACKGROUND

• Hughes BL, Clifton RG, Hauth JC, Leveno KJ, Myatt L, Reddy UM, Varner MW, Wapner RJ, Mercer BM, Peaceman AM, Ramin SM, Tolosa JE, Saade G, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Is Mid-trimester Insulin Resistance Predictive of Subsequent Puerperal Infection? A Secondary Analysis of Randomized Trial Data. Am J Perinatol. 2016 Aug;33(10):983-90. doi: 10.1055/s-0036-1583188. Epub 2016 Apr 27.

  PMID: 27120478 BACKGROUND

• Silver RM, Myatt L, Hauth JC, Leveno KJ, Peaceman AM, Ramin SM, Samuels P, Saade G, Sorokin Y, Clifton RG, Reddy UM. Cell-Free Total and Fetal DNA in First Trimester Maternal Serum and Subsequent Development of Preeclampsia. Am J Perinatol. 2017 Jan;34(2):191-198. doi: 10.1055/s-0035-1570383. Epub 2016 Jul 11.

  PMID: 27398706 BACKGROUND

• Tita AT, Doherty L, Roberts JM, Myatt L, Leveno KJ, Varner MW, Wapner RJ, Thorp JM Jr, Mercer BM, Peaceman A, Ramin SM, Carpenter MW, Iams J, Sciscione A, Harper M, Tolosa JE, Saade GR, Sorokin Y; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Adverse Maternal and Neonatal Outcomes in Indicated Compared with Spontaneous Preterm Birth in Healthy Nulliparas: A Secondary Analysis of a Randomized Trial. Am J Perinatol. 2018 Jun;35(7):624-631. doi: 10.1055/s-0037-1608787. Epub 2017 Nov 30.

  PMID: 29190847 BACKGROUND

• Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, Pearson GD, Wapner RJ, Varner MW, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Samuels P, Sciscione A, Harper M, Smith WJ, Saade G, Sorokin Y, Anderson GB; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010 Apr 8;362(14):1282-91. doi: 10.1056/NEJMoa0908056.

  PMID: 20375405 RESULT

• Hauth JC, Clifton RG, Roberts JM, Spong CY, Myatt L, Leveno KJ, Pearson GD, Varner MW, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Sciscione A, Harper M, Tolosa JE, Saade G, Sorokin Y, Anderson GB; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Vitamin C and E supplementation to prevent spontaneous preterm birth: a randomized controlled trial. Obstet Gynecol. 2010 Sep;116(3):653-658. doi: 10.1097/AOG.0b013e3181ed721d.

  PMID: 20733448 RESULT

Related Links

• The public website of the NICHD Maternal-Fetal Medicine Units (MFMU) Network

MeSH Terms

Conditions

Pre-Eclampsia; Hypertension

Interventions

Dietary Supplements; Vitamins; Ascorbic Acid; alpha-Tocopherol; Vitamin E

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Micronutrients; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Nutrients; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Tocopherols; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. James Roberts
• Organization: Dept of Obstetrics and Gynecology, University of Pittsburgh

RSIJMR@mwri.magee.edu

412-641-1427

Study Officials

• Menachem Miodovnik, MD

  NICHD Project Scientist

  STUDY DIRECTOR

• Rebecca Clifton, Ph.D.

  George Washington University Biostatistics Center

  PRINCIPAL INVESTIGATOR

• James M Roberts, MD

  University of Pittsburgh - Magee Womens

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2005
• First Posted: August 26, 2005
• Study Start: June 1, 2003
• Primary Completion: October 1, 2008
• Study Completion: January 1, 2009
• Last Updated: February 21, 2019
• Results First Posted: November 20, 2018

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share

Locations

US (16)