Tadalafil treatment for preeclampsia (medication in preeclampsia; MIE): a multicenter phase II clinical trial

概要

INTRODUCTION:
Hypertensive disorder of pregnancy (HDP) is a disease that affects prognosis in mothers and fetuses. In industrialized countries, the incidence of preeclampsia is approximately 3-5 per 100 births. Both morbidity and mortality are high for mothers and fetuses; there-fore, it is an important disease for both parties.

OBJECTIVE:
To evaluate the effectiveness of tadalafil treatment for HDP.

METHODS:
In an open-label, randomized c_linical trial, singleton pregnancies with HDP between 20 and 33 weeks of gestation were randomized to take 20 mg oral tadalafil every day (tadalafil treatment group) or no drug (conventional~reatment group). The primary outcome w.as prolongation of pregnancy from randomization to delivery.

RESULTS:
From October 2016 to March 2018, 28 patients were randomized to each group and 2 cases were excluded (tadalafil treatment group: 12 cases; conventional treatment group: 14 cases). There was no difference in the prolongation period of pregnancy that served as primary outcomes in both the groups (17.5 days in tadalafil group vs. 16.5 days in conventional group, p=0.96). The significant adverse events related to tadalafil occurred in the tadalafil treatment group. Among maternal adverse events, specifically with regard to headaches, there were significant differences between the two groups (0% in tadalafil group vs. 43% in c.onventional treatment group; p=0.02).

CONSIDERATION:
In this study, tadalafil did not prolong the gestational period for pregnant women with HDP. However, it did decrease maternal headache which is one of adverse events in HDP. This study had the three limitations. First, it had a small number of participants. Second, this study was an open-label trial. Third, it was interrupted by recom-mendations from the PMDA and could not be accomplished. Based only on these results, it should not be deduced that tadalafil has no efficacy for HDP treatment in humans.

CONCLUSION:
Tadalafil did not prolong the gestational period in pregnant women with HDP. However, maternal headache decreased significantly in the tadalafil treatment group. The timing of administering tadalafil is crucial for HDP prevention and forms the basis for future studies. We aim to conduct tadalafil treatment.trials to prevent HDP in pregnant women with high risk of the disease while incorporating appropriate medication adminis-tration time into the study protocols.