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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Prospective Randomized Double-Blind, Placebo Controlled Evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia

Brief Summary: The purpose of the study is to assess the efficacy, safety and pharmacokinetics (PK) of recombinant human antithrombin (ATryn) in addition to expectant management for the treatment of preterm preeclampsia (PPE). Efficacy will be assessed by comparing the difference in extension of gestational age from the time of randomization into the study until delivery between ATryn and placebo treated subjects. In addition, the effect of ATryn on fetal and neonatal clinical outcomes will be assessed. The PK characteristics of ATryn in the subjects will be investigated by measuring AT activity levels in the mother during treatment and in cord blood.

Detailed Summary:

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 wee
Sponsor: rEVO Biologics

Current Primary Outcome: The primary outcome measure is the increase in gestational age. [ Time Frame: 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. ]

Increase in gestational age is defined as the gestational age at delivery minus the gestational age at randomization.


Original Primary Outcome: Same as current

Current Secondary Outcome: The secondary outcome measure is a composite measure of specific fetal and neonatal outcomes. [ Time Frame: 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 and for the neonate until 36 weeks post menstrual age. ]

The specific fetal and neonatal outcomes include bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leucomalacia, retinopathy of prematurity, late Sepsis, necrotizing enterocolitis and mortality (fetal and neonatal). The outcome is measured on a 5 point scale.


Original Secondary Outcome: Same as current

Information By: rEVO Biologics

Dates:
Date Received: February 6, 2014
Date Started: July 11, 2014
Date Completion:
Last Updated: February 7, 2017
Last Verified: February 2017