Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)
Status:
Recruiting
Trial end date:
2023-06-30
Target enrollment:
Participant gender:
Summary
Pregnancy in sickle cell disease (SCD) is fraught with many complications including
preeclampsia (PE) and intrauterine growth restriction (IUGR). Previously, the investigators
found an abnormality in prostacyclin-thromboxane ratio in sickle cell pregnant women, a
situation that is also found in non-sickle pregnancies with PE and unexplained IUGR. Low dose
aspirin (LDA) has been found to reduce the incidence of PE and IUGR in high-risk women due to
its reduction of vasoconstrictor thromboxane whilst sparing prostacyclin, in effect
"correcting" the ratio. It has been found to be safe for use in pregnancy and is recommended
in obstetric guidelines for this use but has not been tested in sickle cell pregnancy. The
investigators hypothesize that LDA would reduce the incidence of IUGR and PE in pregnant
haemoglobin (Hb)SS women. The investigators also plan to build a machine-learning model to
predict severe maternal outcomes in them.
The investigators propose a multi-site, randomized, controlled, double blind trial comparing
a daily dose of 100mg aspirin with placebo, from 12 - 28 weeks gestation until 36 weeks. The
study sites are three teaching hospitals in Lagos and Ile-Ife, and twelve general hospitals
and one federal medical centre within Lagos state, with the coordinating centre at the
College of Medicine, University of Lagos (CMUL), Idi-Araba, Lagos. A total of 476 eligible
pregnant HbSS and HbSC women will be recruited consecutively and randomly assigned to either
group using a web-based app, sealed envelope. Each study group will comprise 238 pregnant
women with SCD.
All participants will be followed from recruitment till delivery. They will have their body
weight, blood pressure and haematocrit checked at each antenatal visit. Their full blood
count, vital signs and oxygen saturation will be checked and recorded at each visit. Primary
outcome measure will be birth weight below 10th centile for gestational age on INTERGROWTH 21
birthweight charts, and incidence of miscarriage or perinatal death. Analysis will be by
intention to treat, and the main treatment effects will be quantified by relative risk with
95% confidence intervals, at a 5% significance level. The investigators plan to develop a
prediction model to predict the risk of complications in these women using machine learning.
The prediction outcome will be severe maternal outcomes comprising maternal near miss or
death.