Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)

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 six weeks postpartum. 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.

Conditions

• Intrauterine Growth Restriction
• Preeclampsia
• Sickle Cell Disease
• Pregnancy Complications

Interventions

DRUG

Low-dose aspirin

Low dose aspirin (LDA) group will receive 100mg aspirin daily taken at once just before bedtime from 12 weeks gestational age or enrollment till 36 weeks gestational age.

OTHER

Placebo

Placebo group will receive one tablet of the placebo which has same shape, size, thickness and colour as the LDA daily taken at once just before bedtime from 12 weeks gestational age or enrollment till 36 weeks gestational age.

Sponsors & Collaborators

• University of Lagos, Nigeria

  lead OTHER

Principal Investigators

• Bosede B Afolabi, DM (Nott) · College of Medicine, University of Lagos

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-07-01

Primary Completion

2024-10-29

Completion

2024-11-21

Countries

• Nigeria

Study Locations