EPPI Trial Information
Preeclampsia and small-for-gestational-age pregnancy are major causes of maternal and perinatal morbidity and mortality. Women with a previous pregnancy affected by these conditions are at an increased risk of recurrence in a future pregnancy. Past trials evaluating the effect of low-molecular-weight heparin for the prevention of recurrence of preeclampsia and small-for-gestational-age pregnancy have shown conflicting results with high levels of heterogeneity displayed when trials were compared.
We sought to assess the effectiveness of enoxaparin in addition to high-risk care for the prevention of preeclampsia and small for gestational age pregnancy in women with a history of these conditions.
This was an open-label randomized controlled trial in 5 tertiary care centers in 3 countries.
Women with a viable singleton pregnancy were invited to participate between 6 and 16 weeks if deemed to be at high risk of preeclampsia and/or small for gestational age based on their obstetric history.
Participants received either standard high-risk care or standard high-risk care plus enoxaparin 40 mg (4000 IU) by subcutaneous injection daily from recruitment until 36 weeks or delivery, whichever occurred sooner. Standard high-risk care was defined as care coordinated by a high-risk antenatal clinic service, aspirin 100 mg daily until 36 weeks, and for women with prior preeclampsia calcium 1000-1500 mg daily until 36 weeks.
The primary outcome was a composite of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile.
Secondary outcomes include:
Secondary outcomes included preeclampsia, severe preeclampsia, HELLP syndrome (hemolysis, elevated liver enzyme, and low platelet count), eclampsia, gestational hypertension, SGA <10th percentile, SGA <5th percentile, SGA <3rd percentile, placental abruption and antepartum hemorrhage, thrombocytopenia (platelet count <100 x 109/L) while on LMWH, stillbirth, induction of labor, caesarean delivery, postpartum hemorrhage, gestational age at birth, preterm birth, mean birthweight and mean birthweight percentile, neonatal death, neonatal intensive care admission and duration of admission, a composite outcome of severe neonatal morbidity (evidence of 1: intraventricular hemorrhage [grade 3 and4], cystic periventricular leukomalacia, chronic lung disease, retinopathy of prematurity requiring treatment, or necrotizing enterocolitis requiring surgery), and maternal serum levels of sFlt-1, sEng, PlGF, sVCAM-1, and ET-1.
We planned for a sample size of 160 participants (80 participants in each group, including a 5% dropout/early miscarriage rate) to achieve 80% power at a 2-sided significance level of .05 to detect a difference between 25-7%. All data were analyzed on an intention-to-treat basis.
Statistical models were adjusted for thrombophilia status, recruitment center, inclusion criteria, and number of previous preeclampsia/SGA events. Multiple logistic regression was used to analyze the binary primary and secondary outcomes. Multiple linear regression was used to analyze the continuous secondary outcomes.
Investigators and Primary Contacts
Chief Investigator: Katie Groom, University of Auckland, firstname.lastname@example.org
ClinicalTrialManager: Laura Mackay, University of Auckland, email@example.com
Australia New Zealand Clinical Trials Registry
(ANZCTR) Trial Registry Number: ACTRN12609000699268
University of Auckland Faculty Research Development Fund
Auckland District Health Board Charitable Trust
Australasian Society of Thrombosis and Hemostasis Scientific and Education Trust
University of Auckland School of Medicine Performance based Research Fund