High dose antithrombin supplementation in early preeclampsia: A randomized, double blind, placebo-controlled study

Area of Science:

• Obstetrics and Gynecology
• Maternal-Fetal Medicine
• Pharmacology

Background:

• Reduced antithrombin levels are observed in preeclampsia.
• Antithrombin concentrate infusion may prolong gestation in severe preeclampsia.

Purpose of the Study:

• To evaluate the efficacy and safety of high-dose antithrombin (ATIII) supplementation.
• To assess its impact on maternal and fetal/neonatal outcomes in early preeclampsia (before 30 weeks gestation).

Main Methods:

• A double-blind, placebo-controlled trial (KB033) involving 13 Italian centers.
• Randomization of 38 evaluable patients to high-dose AT (3000 IU/daily) or placebo for up to 7 days.
• Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted.

Main Results:

• The trial was terminated early due to low enrollment (38 patients vs. planned 240).
• No significant difference in composite perinatal morbidity between AT and placebo groups (ITT: RR 0.85, PP: RR 0.79).
• Maternal AT supplementation was linked to reduced blood loss and improved laboratory markers (LDH, d-dimer).

Conclusions:

• The trial was markedly underpowered to detect significant differences in perinatal outcomes.
• Suggestive evidence of potential maternal benefits from AT supplementation.
• Results do not support high-dose AT supplementation for improving fetal/neonatal outcomes in early preeclampsia.