Early prediction and aspirin for prevention of pre-eclampsia (EPAPP) study: a randomized controlled trial.
OBJECTIVE
To estimate the effect of early administration of aspirin on the prevention of pre-eclampsia in high-risk women.


METHODS
This was planned as a randomized, double-blind, placebo-controlled trial of aspirin for women with risk factors for pre-eclampsia. Participants were randomized to start either aspirin (81 mg/day) or placebo at 11 + 0 to 13 + 6 weeks of gestation. The primary outcome was pre-eclampsia and secondary outcomes included gestational hypertension and small-for-gestational age at birth.


RESULTS
The trial suffered from slow recruitment, leading to a protocol change to broaden the inclusion criteria (from a minimum score of multiple risk factors to at least one risk factor for pre-eclampsia). The trial was then terminated prematurely due to continuing slow recruitment and a lack of equipoise given a change in national guidelines to administer aspirin to high-risk women. From the 53 women who were randomized, 30 were included in the final analysis. There was no evidence that the primary outcome of pre-eclampsia was prevented by low-dose aspirin (relative risk (RR) 0.88, 95% CI 0.21-3.66). Gestational hypertension was seen in two women, both in the aspirin group. There was no evidence that the occurrence of small-for-gestational age was reduced by aspirin (RR 0.88, 95% CI 0.06-12.72).


CONCLUSIONS
Although this study was underpowered to show effectiveness of aspirin compared to placebo due to the premature termination and difficulties encountered, it highlights practical issues to inform future studies.
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL, USA.
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Odibo
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO, USA.
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KR
Goetzinger
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL, USA.
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L
Odibo
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO, USA.
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MG
Tuuli
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005865:Gestational Age; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011225:Pre-Eclampsia / Q000517:prevention & control*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D047928:Premature Birth / Q000517:prevention & control; D012307:Risk Factors; D016216:Ultrasonography, Prenatal
D010975:Platelet Aggregation Inhibitors; D001241:Aspirin
ASA; acetylsalicylic acid; aspirin; high-risk; pre-eclampsia