PreeclampsiaPhase 3CAPPSNCT00135707
Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)
A Phase 3 study testing Dietary Supplement/Vitamins in people with Preeclampsia, run by The George Washington University Biostatistics Center at 16 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preeclampsia
- What is being tested?
- Dietary Supplement/Vitamins
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10,154 participants
- Where
- 16 sitesUnited States
- Study dates
- Jun 2003to Jan 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 14Show fewer
- 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 locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
University of Alabama - Birmingham
Birmingham, Alabama, 35233
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Case Western University
Cleveland, Ohio, 44109
Ohio State University
Columbus, Ohio, 43210
University of Texas - Southwest
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
University of Texas Medical Branch
Galveston, Texas, 77555
University of Texas - Houston
Houston, Texas, 77030
Columbia University
New York, New York, 10032
Drexel University
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
Oregon Health and Sciences University
Portland, Oregon, 97239
Brown University
Providence, Rhode Island, 02905
University of Utah Medical Center
Salt Lake City, Utah, 84132
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Official title: A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia and An Observational Cohort Study to Predict Preeclampsia
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).
Read the 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.
- Conditions
- Preeclampsia
- Being tested
- Dietary Supplement/Vitamins, Placebo for Vitamin C and Vitamin E
- Keywords
- Antioxidants, Preeclampsia, Pregnancy, Hypertension
- Medical subject headings
- Pre-Eclampsia, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary Supplement/VitaminsDrug
Also called Ascorbic Acid and d-alpha-Tocopheryl Acetate
Vitamin C (1000 mg) and Vitamin E (400 IU) per capsule, two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery.
Placebo for Vitamin C and Vitamin EDrug
Placebo two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo for Vitamin C and Vitamin E |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 20 weeks through discharge or prior to discharge following delivery admission
Secondary outcomes (27)
Preeclampsia (Mild, Severe, HELLP Syndrome, Eclampsia)
HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.
Measured: 20 weeks through discharge following delivery
Pregnancy Associated Hypertension
Measured: 20 weeks through discharge following delivery
Medically Indicated Delivery Because of Hypertension
Measured: 20 weeks through discharge following delivery
Aspartate Aminotransferase ≥100 U/Liter
Measured: 20 weeks through discharge
Creatinine ≥1.5 mg/dl (133 μmol/Liter)
Measured: 20 weeks through discharge
Antepartum Bleeding
Measured: During pregnancy
Premature Rupture of Membranes
Measured: During pregnancy
Placental Abruption
Measured: During pregnancy
Cesarean Delivery
Measured: Delivery
Maternal Death
Measured: Delivery through hospital discharge
Postpartum Pulmonary Edema
Measured: After delivery through discharge
Hematocrit ≤24% With Transfusion
Measured: Delivery admission to discharge
Maternal Hospital Stay
Measured: Delivery through discharge
Gestational Age at Delivery
Measured: Delivery
Preterm Birth
Measured: Delivery
Fetal or Neonatal Death
Measured: During pregnancy or thorugh discharge
Birth Weight
Measured: At birth
Small for Gestational Age
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)
Measured: At birth
Birth Weight <2500 Grams
Measured: At birth
Admission to NICU
NICU denotes neonatal intensive care unit.
Measured: Delivery through discharge
Respiratory Distress Syndrome
Measured: Delivery through discharge
Intraventricular Hemorrhage, Grade III or IV
Measured: Delivery through discharge
Sepsis
Measured: Delivery through discharge
Necrotizing Enterocolitis
Measured: Delivery through discharge
Retinopathy of Prematurity
Measured: Within 1 month of birth
Apgar Score <=3 at 5 Minutes
Measured: At birth
Neonatal Hospital Stay
Measured: Birth through discharge from hospital
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2005 (estimated)
- Study startJun 2003
- Primary completionOct 2008
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for PreeclampsiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 10,154 participants (actual)
Sponsor and investigators
- Lead sponsor
- The George Washington University Biostatistics Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Menachem Miodovnik, MD, Study director, NICHD Project ScientistRebecca Clifton, Ph.D., Principal investigator, George Washington University Biostatistics CenterJames M Roberts, MD, Study chair, University of Pittsburgh - Magee Womens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00135707
- Sponsor's protocol ID
- HD36801-CAPPS
- Other IDs
- U10HD021410, U10HD027869, U10HD027917, U10HD027860, U10HD027915, U10HD034116, U10HD034208, U10HD034136
- Acronym
- CAPPS
- Status last verified
- Feb 2019
- First submitted
- 24 Aug 2005
- Last updated
- 21 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 21458622Carreno 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.
PubMed 22617588Myatt 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.
PubMed 22617589Myatt 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.
PubMed 22996099Weissgerber 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.
PubMed 23573260Johnson 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.
PubMed 23635732Myatt 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.
PubMed 23331974Makhlouf 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.
PubMed 24347257Cantu 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.
PubMed 25437721Weissgerber 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.
PubMed 24345080Abramovici 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.
PubMed 25516497Basraon 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.
PubMed 26352680McDonnold 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.
PubMed 26788786Hughes 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.
PubMed 27120478Silver 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.
PubMed 27398706
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of Antioxidants to Prevent Preeclampsia and An Observational Cohort Study to Predict Preeclampsia
- ClinicalTrials.gov ID
- NCT00135707
- Acronym / sponsor ID
- CAPPS / HD36801-CAPPS
- Conditions
- Preeclampsia
- Keywords
- Antioxidants, Preeclampsia, Pregnancy, Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10,154 participants (actual)
- Lead sponsor
- The George Washington University Biostatistics CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jun 2003
- Primary completion
- Oct 2008 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 26 Aug 2005 (estimated)
- Results
- Posted 20 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dietary Supplement/Vitamins | Experimental | Drug: Dietary Supplement/Vitamins1000mg of Vitamin C and 400IU of Vitamin E per capsule, twice daily between randomization (at 9 to 16 weeks) up to delivery. |
| Placebo for Vitamin C and Vitamin E | Placebo comparator | Drug: Placebo for Vitamin C and Vitamin EPlacebo 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. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dietary Supplement/VitaminsAlso: Ascorbic Acid and d-alpha-Tocopheryl AcetateVitamin C (1000 mg) and Vitamin E (400 IU) per capsule, two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery. | Drug | Dietary Supplement/Vitamins |
| Placebo for Vitamin C and Vitamin EPlacebo two capsules daily between randomization (at 9 - 16 weeks gestation) up to delivery. | Drug | Placebo for Vitamin C and Vitamin E |
Primary outcome
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.
27 secondary outcomes
Preeclampsia (Mild, Severe, HELLP Syndrome, Eclampsia)
Time frame: 20 weeks through discharge following delivery
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
Birth Weight <2500 Grams
Time frame: At birth
Admission to NICU
Time frame: Delivery through discharge
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21458622Hauth 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.
- Background: PubMed 22617588Carreno 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.
- Background: PubMed 22617589Myatt 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.
- Background: PubMed 22996099Myatt 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.
- Background: PubMed 23573260Weissgerber 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.
- Background: PubMed 23635732Johnson 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.
- Background: PubMed 23331974Myatt 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.
- Background: PubMed 24347257Makhlouf 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.
- Background: PubMed 25437721Cantu 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.
- Background: PubMed 24345080Weissgerber 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.
- Background: PubMed 25516497Abramovici 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.
- Background: PubMed 26352680Basraon 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.
- The public website of the NICHD Maternal-Fetal Medicine Units (MFMU) NetworkLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Menachem Miodovnik, MD study director
NICHD Project Scientist
Rebecca Clifton, Ph.D. principal investigator
George Washington University Biostatistics Center
James M Roberts, MD study chair
University of Pittsburgh - Magee Womens
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dietary Supplement/Vitamins in people with Preeclampsia, run by The George Washington University Biostatistics Center at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate (time frame: 20 weeks through discharge following delivery). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00135707, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2019.