The PIPSCKLE Trial Outcomes: What Low-Dose Aspirin Means for Pregnancy in Women with Sickle Cell Disease.

What is PIPSICKLE trial?

The PIPSCKLE trial is a TETFund (Nigeria)-funded research study that stands for “Preventing Intrauterine Growth Restriction and Pre-eclampsia in Sickle Cell Pregnancy.” Its objective is to evaluate preventive strategies to reduce key pregnancy complications—including intrauterine growth restriction (IUGR), stillbirth, miscarriage, and pre-eclampsia (a dangerous pregnancy condition involving new high blood pressure and organ damage) —in women with sickle cell disease.

About the research study

We conducted a randomized, double-blind, parallel-group, superiority trial. Eligible participants were pregnant women (aged ≥18 years) with HbSS or HbSC genotype, carrying a singleton fetus at 12–28 weeks gestation. A total of 476 consenting participants were recruited from 16 healthcare facilities across Lagos and Osun States, Nigeria. They were randomly assigned (1:1) to receive either 100 mg of low-dose aspirin (LDA) or an identical-looking placebo daily. Active participants’ recruitment and follow up was from July 1, 2020, to December 11, 2024, when the last participant completed six weeks postpartum follow up visit.

What did we find out?

This study represents the largest clinical trial to date on pregnancy in sickle cell disease (SCD) globally, providing essential evidence for a population traditionally excluded from research. Our findings diverge from data in the general obstetric population; we observed no significant benefit of low-dose aspirin (LDA) in preventing a composite of adverse pregnancy outcomes (IUGR, miscarriage, perinatal death, preeclampsia, preterm birth) or in reducing common medical complications (UTIs, pneumonia, sepsis, transfusion need). Notably, analysis of sickle cell specific complications revealed that LDA did not reduce the risk of vaso-occlusive crises, hemolytic crisis or acute chest syndrome, and may actually increase these risk.

Implication of the findings

This study provides pivotal clinical evidence, demonstrating that low-dose aspirin (LDA) confers no benefit in preventing major adverse pregnancy outcomes including intrauterine growth restriction, preeclampsia, and perinatal death among pregnant women with sickle cell disease. These results directly counter established guidelines for the general obstetric population.

Crucially, the findings raise significant safety considerations, indicating a need for caution in prescribing LDA to this cohort. They suggest that a routine intervention may inadvertently exacerbate specific sickle cell related complications.

Ultimately, this research underscores a fundamental imperative: to achieve equitable and effective care, pregnant women with SCD must be intentionally included in clinical trials. Population-specific evidence is essential to develop safe, relatable guidelines that genuinely improve maternal and fetal health outcomes.

What next

The full details and findings from this study will be published in The Lancet Global Health and will be available to the general public on the 17^th of February, 2026.  In addition, several studies within the trial are currently in the publication pipeline and will provide further insights into other findings from the study.

For further enquiries, questions, or if you would like to be notified when the papers are published, please contact the Centre for Clinical Trials Research and Implementation Science (CCTRIS) University of Lagos, the coordinating centre for the PIPSICKLE Trial on the following numbers: 08033966882 or 08188339571. You may also send an email to info@pipsickletrial.com  or info@cctris.org  or visit our website www.cctris.org . Also, you can follow CCTRIS across all social media platforms for updates using this link www.linktr.ee/CCTRIS

Acknowledgement

This research is supported by Tertiary Education Trust Fund (TETFund), Abuja, Nigeria.

We are grateful to all the women who participated in the study, the Sickle Cell Clubs across Lagos State for collaborating with us and spreading the messages concerning this research. We appreciate all Site Coordinators, Research Nurses, Haematologists, Data Officer and all other collaborators for their support.