Pharmacokinetics, Safety and Efficacy Study of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia (PRESERVE-1)
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.
Biological: Recombinant human antithrombin (ATryn)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Prospective Randomized Double-Blind, Placebo Controlled Evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia (PRESERVE-1)|
- 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. ] [ Designated as safety issue: No ]Increase in gestational age is defined as the gestational age at delivery minus the gestational age at randomization.
- 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. ] [ Designated as safety issue: Yes ]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.
- Other outcomes include individual maternal, perinatal and neonatal outcomes.In addition, a second neonatal composite outcome score, the avoidance of all morbidity and mortality will be examined [ 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 post menstrual age. ] [ Designated as safety issue: Yes ]These outcomes will be summarized using counts and percentages, and exact (Clopper-Pearson) 95% confidence intervals for the true proportions will be calculated for each treatment.
|Study Start Date:||May 2014|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Recombinant Human Antithrombin (ATryn)
ATryn 250 mg loading dose over 15 minutes, immediately followed by continuous infusion of 2000 mg per 24 hours. Total daily dose is 2250 mg for the first day and 2000 mg on subsequent days
Biological: Recombinant human antithrombin (ATryn)
Atryn 250 mg loading dose over 15 minutes, immediately followed by continuous infusion of 2000 mg per 24 hours. Total daily dose is 2250 mg for the first day and 2000 mg on subsequent days
Other Name: Recombinant human antithrombin (rhAT)
Placebo Comparator: Normal Saline 0.9%
Placebo (Normal Saline 0.9%, matched for volume of active treatment) consisting of a loading dose over 15 minutes followed by continuous infusion.
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. A 12/24-hour urine collection for protein or protein/creatinine ratio will be collected if not available at the time of screening. 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 approximately 4-6 weeks after delivery of the neonate. Information on the neonates will be collected until they reach a post-menstrual age of 36 weeks (and a minimum of 28 days post delivery).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02059135
|Contact: Laura Massey, BSemail@example.com|
|Contact: Denise Tilton, RN, MHAfirstname.lastname@example.org|
|United States, Alabama|
|University of Alabama||Recruiting|
|Birmingham, Alabama, United States, 35210|
|United States, Connecticut|
|Yale New Haven Hospital||Not yet recruiting|
|New Haven, Connecticut, United States, 06519|
|United States, Tennessee|
|Erlanger Medical Center||Recruiting|
|Chattanooga, Tennessee, United States, 347403|
|Principal Investigator:||Michael Paidas, MD||Yale New Haven Health System Center for Healthcare Solutions|