LAS VEGAS (Jan. 23, 2017)--In a study to be presented Friday, Jan. 27, in the late breaking oral session at 10 a.m. PST, at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting™, researchers with The PRESERVE-1 Study Group University of Texas Health Science Center at Houston--McGovern Medical School, Houston, Texas, and Yale School of Medicine, New Haven, Connecticut, present findings of a study titled Randomized double-blind placebo controlled evaluation of the safety and efficacy of recombinant Antithrombin versus placebo in preterm preeclampsia. The study was sponsored by rEVO Biologics, Inc.
Preeclampsia is a major cause of maternal and perinatal mortality and morbidity. In addition, women who develop early onset preeclampsia have markedly increased rate of complications both acute and long term such as cardiovascular disease, stroke, renal injury and metabolic syndrome. Infants born at less than 30 weeks have significant neonatal complications with prolonged stays in the neonatal intensive care unit. In addition, they are at increased risk for chronic lung disease, cerebral palsy and other neurologic deficits. There are approximately 8,000 cases of early onset preeclampsia each year in the U.S. The estimated maternal and neonatal cost of these pregnancies is almost $1.5 billion.
This trial investigated the effects of recombinant antithrombin (ATryn®), a man-made version of antithrombin, a protein molecule found in blood that is produced by the liver, regulates the coagulation system, and has anti-inflammatory properties. It was studied to determine its potential to prolong gestation and improve maternal and neonatal outcomes. The study's design was remarkable in that it was the largest randomized, controlled trial ever to be completed in patients who developed preeclampsia very early in pregnancy, 23-30 weeks' gestational age.
Baha Sibai, M.D. with the University of Texas Health Science Center at Houston and the presenter of the study at the SMFM annual meeting, reported "The results found no improvement in outcomes with such therapy. There were no reported safety events related to Recombinant Antithrombin" Future studies should investigate different novel targeted therapies to improve outcome in such pregnancies."
About the Society for Maternal-Fetal Medicine
The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine. The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed. For more information visit http://www.smfm.org.
Abstract LB02 Randomized double-blind placebo controlled evaluation of the safety and efficacy of recombinant Antithrombin versus placebo in preterm preeclampsia Baha Sibai¹ , Michael J. Paidas² , The PRESERVE Study Group ¹University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, ²Yale School of Medicine, New Haven, CT
OBJECTIVE: Antithrombin's (AT) anti-inflammatory and anticoagulant properties along with prior clinical evidence support AT as a potential therapy for preeclampsia (PreE). We studied recombinant AT (rhAT) in a multi-center study to determine if rhAT could extend the duration of pregnancy and decrease neonatal morbidity in expectantly managed patients with early onset PreE.
STUDY DESIGN: We performed a double-blind, placebo controlled trial at 23 tertiary hospitals. Women were eligible if they had a singleton pregnancy, early onset PreE/superimposed PreE at 23 0/7 to 30 0/7 wks, and deemed stable for expectant management. Antihypertensives, magnesium sulfate and steroids were used as indicated. Patients were randomized 1:1 to receive either rhAT 250 mg loading dose followed by a continuous infusion 2000mg/24hours or an identical saline infusion. The infusion was continued until delivery. Specific predefined outcomes of interest were assessed in both mother and neonate (through 36 weeks post menstrual age). The primary efficacy endpoint was median increase in gestational age (GA) from randomization until delivery. The secondary efficacy endpoint was a composite neonatal outcome score (Image 1). Safety was assessed through laboratory and adverse event review. A sample size of 120 was required.
RESULTS: 120 were randomized: 62 rhAT and 58 placebo. There were no differences between groups in median GA at enrollment (27.6 vs 27.3 for placebo vs rhAT respectively), demographics, or rate of superimposed PreE. Mean baseline % AT activity was similar between groups and much higher than anticipated (93% vs 95% for placebo vs rhAT respectively). There were no differences between groups in primary outcome or composite neonatal score (Table). Results remained the same in pre-specified subgroups: GA at enrollment (<27 vs > 27), PreE vs superimposed PreE. Finally, there were no significant differences in maternal complications such as pulmonary edema, eclampsia, or HELLP syndrome. There were no reported safety events related to rhAT.
CONCLUSION: Administration of rhAT in early onset PreE was not associated with pregnancy prolongation nor improved maternal/ neonatal outcomes.