Prospective Randomized Double-Blind, Placebo Controlled Evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia (PRESERVE-1)

ABSTRACT Background Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin displays anti-inflammatory and anticoagulant properties and thus may have a therapeutic role treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation and activation of the coagulation system. Study Design and Objectives We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks, and expectant management was planned. In addition to standard therapy, patients were randomized to receive either recombinant antithrombin 250 mg loading dose followed by a continuous infusion 2000mg/24hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. Secondary outcome was composite neonatal morbidity score. 120 women were randomized. Results There was no difference in median gestational age at enrollment (27.3 weeks for the recombinant antithrombin group [range 23.1-30.0] and 27.6 weeks for the placebo group, [range 23.0-30.0], respectively, p value 0.67. There were no differences in median increase in days gained (5.0 in the recombinant antithrombin group [range 0-75] and 6.0 for the placebo group [range 0-85], p value 0.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiologic antithrombin concentrations. Conclusions Administration of recombinant antithrombin in preterm preeclampsia was not associated with pregnancy prolongation, nor in improved neonatal or maternal outcomes.