Trial of calcium for preeclampsia prevention (CPEP): Rationale, design, and methods

• Published in: Controlled clinical trials 1996-10, Vol.17 (5), p.442-469
• Main Authors: Levine, Richard J., Esterlitz, Joy R., Raymond, Elizabeth G., DerSimonian, Rebecca, Hauth, John C., Curet, L.Ben, Sibai, Baha M., Catalano, Patrick M., Morris, Cynthia D., Clemens, John D., Ewell, Marian G., Friedman, Steven A., Goldenberg, Robert L., Jacobson, Sig-Linda, Joffe, Gary M., Klebanoff, Mark A., Petrulis, Alice S., Rigau-Perez, Jose G.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; calcium; Calcium - adverse effects; Calcium - therapeutic use; Clinical trial; Double-Blind Method; Female; Genital system. Reproduction; Humans; hypertension; Hypertension - diagnosis; Management Information Systems; Medical sciences; Multicenter Studies as Topic - methods; Multicenter Studies as Topic - statistics & numerical data; Nutrition Assessment; Patient Compliance; Patient Selection; Pharmacology. Drug treatments; Placebos; Pre-Eclampsia - diagnosis; Pre-Eclampsia - prevention & control; preeclampsia; Pregnancy; Pregnancy Complications, Cardiovascular - diagnosis; proteinuria; Quality Control; Random Allocation; Randomized Controlled Trials as Topic - methods; Randomized Controlled Trials as Topic - statistics & numerical data; Research Design; Sample Size; Severity of Illness Index; Statistics as Topic; United States; Urinary Calculi - diagnosis; Urinary Calculi - etiology; Urinary Calculi - prevention & control
• ISSN: 0197-2456; 1879-050X
• DOI: 10.1016/S0197-2456(96)00106-7

The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily ( n = 2295) or placebo ( n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32–33 weeks gestation. This report describes the study rationale, design, and methods.