Pharmacokinetics, Safety and Efficacy Study of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia

Hospitalized PPE patients who are being expectantly managed, after initial assessment and stabilization period, will be considered for the study. After informed consent has been obtained subjects will be screened for eligibility. Screening includes obtaining the subject's medical/obstetric history and a physical examination which includes an assessment of maternal and fetal status. Blood samples for hematology, clinical chemistries, biomarkers, coagulation, immunogenicity and AT activity levels will be drawn. Urine will be collected for baseline urinalysis, protein/creatinine ratio and biomarkers. Eligible subjects who meet inclusion/exclusion criteria will be randomized in a 1:1 ratio to receive a continuous infusion of either ATryn or placebo. Sampling for AT activity will be performed immediately prior to the first dose of study drug and at specified times thereafter. Subjects will continue on study drug until maternal and/or fetal indications for delivery necessitate cessation of expectant management or until 34 0/7 weeks of gestation. The average extension of pregnancy with standard of care expectant management in this patient population is approximately 7 days. It is assumed that treatment with ATryn will provide an additional increase in gestational age of 5-7 days as compared to this standard of care. Total duration on study drug is therefore estimated to be approximately 7 to 14 days on average. Post treatment assessments of the mother will be performed at hospital discharge and approximately 4-6 weeks after delivery of the neonate. Information on the neonates will be collected until they reach a post-menstrual age (PMA) of 36 weeks. If the neonate reaches 36 weeks PMA \< 28 days following delivery, the final neonatal follow-up visit should be done at the 4-6 week post-delivery visit. After the primary study completion and follow-up period, the neonate total number of days in the Neonatal Intensive Care Unit (NICU), days on a ventilator, days requiring supplemental oxygen (FiO2 ≥21%),the neonate hospital discharge date and whether the neonate is discharged from the hospital with a requirement for supplemental home oxygen therapy will be collected to help assess health care utilization. In addition, the date of death will be collected if the neonate expires before hospital discharge. These data will be considered supplemental to the primary study data set.