Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)

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).

Timeline

Start

2003-06

Primary completion

2008-10

Completion

2009-01

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Results 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.
• Results 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.

Drugs

Indications