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: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Lagos, Nigeria
• Treatments: Aspirin

Criteria

Inclusion Criteria:

• Age 18 years and above

• Singleton fetus

• Women whose genotypes are Haemoglobin SS or SC.

• 28 weeks gestation or less at recruitment, estimated from the last menstrual period or by an early ultrasound scan.

Exclusion Criteria:

• Women with associated medical conditions in pregnancy e.g., HIV infection, diabetes mellitus, hypertension, renal disease, sickle nephropathy

• Multiple pregnancy

• Hypersensitivity to aspirin

• History of blood transfusion in the last 3 months