Randomized Study of Antithrombin in Early-Onset Preeclampsia: KOUNO-TORI Study.

BACKGROUND

In preeclampsia, prolonging pregnancy decreases the risks of fetal morbidity and death. This study aimed to evaluate the efficacy and safety of antithrombin in prolonging pregnancy early-onset severe preeclampsia.

METHODS

This was a randomized, double-blind, placebo-controlled study involving women with early-onset preeclampsia from 61 institutions. Participants developed early-onset severe preeclampsia from 24+0 to 31+6 weeks' gestation and had ≤100% antithrombin activity. Two groups were created, with random and blinded assignment of the participants 1:1 to a placebo (saline) group (n=92) or a recombinant human antithrombin-gamma (rhAT-gamma) group (n=90). The number of days from treatment initiation to delivery was recorded in each group, as the primary end point.

RESULTS

Pregnancy was prolonged by 13 days (95% CI, 10.4-15.6) in the placebo group and 16.9 days (95% CI, 13.8-20.0) in the rhAT-gamma group (P=0.07). Compared with the placebo group, hemorrhage-related adverse events occurred at a 19.0% higher rate in the rhAT-gamma group (mean difference [95% CI, 4.3%-32.7%]), and anemia occurred at a 16.8% higher rate (mean difference [95% CI, 2.0%-30.6%]).

CONCLUSIONS

No significant difference in pregnancy prolongation was found between the placebo and rhAT-gamma participants with early-onset severe preeclampsia. However, compared with the placebo group, the rhAT-gamma group appeared to have higher rates of hemorrhage-related adverse events and anemia.

REGISTRATION: URL: https://jrct.niph.go.jp/en-top; Unique identifier: jRCT2080224912. URL: https://clinicaltrials.gov/; Unique identifier: NCT04182373.