| Protocol No: | ECCT/24/04/07 | Date of Protocol: | 22-11-2023 |
| Study Title: | PEARLS FORMATIVE (Preventing pre-eclampsia: Evaluating AspiRin Low-dose regimens following risk Screening) |
| Study Objectives: | Objective 1: We aim to implement and optimize pre-eclampsia risk screening in Ghana, Kenya, and South Africa by adapting The Tommy's App for these settings. Healthcare providers will be trained to use the app for screening pregnant women attending antenatal care before 20 weeks' gestation. We will collect quantitative data on training, facility-level information, and individual women's data on pre-eclampsia risk indicators. To address implementation challenges, we will conduct rapid stakeholder interviews at selected health facilities, analyzing data concurrently and using a combined approach for the analysis of anonymized focus group discussion transcripts.
Objective 2: We will evaluate the prevalence of trial primary outcomes by conducting a retrospective review of medical records at key hospitals in Ghana, Kenya, and South Africa, where the majority of trial participants will give birth. Trained research staff will enter non-identifiable data from the retrospective review.
Objective 3: We aim to assess and align current clinical practices for pre-eclampsia screening, prevention, and management in study sites. This involves a desk review of guidelines and clinical protocols from all countries and study sites, organized in an analysis matrix and compared to WHO guidelines. Maternity healthcare providers in study facilities will complete an electronic survey to gather self-reported data on their current clinical care practices and views on potential barriers to pre-eclampsia risk screening and the upcoming randomized trial.
Objective 4: We will assess the willingness and potential barriers for women and care providers to participate in the main trial. Focus group discussions (FGDs) with high-risk women identified through the screening algorithm and healthcare providers will explore barriers and facilitators to pre-eclampsia risk screening and trial participation, communication needs of women regarding risk screening, and potential obstacles and facilitators for the use of low-dose aspirin or low-dose calcium. Analysis of anonymized FGD transcripts will use a combined approach of inductive thematic and deductive framework analysis. |
| Laymans Summary: | PEARLS trial is a multi-country, multi-centre, placebo-controlled, randomised trial in Ghana, Kenya and South Africa, comparing efficacy and safety of two doses of aspirin to prevent pre-eclampsia in women at increased risk pre-eclampsia. An app-based system will be used to screen pregnant women for risk of pre-eclampsia in participating sites. Women identified as high risk and who are otherwise eligible will be invited to provide informed consent for a randomised trial of 75mg or 150 mg/day of aspirin. The trial will assess the effects of different aspirin on preventing preterm pre-eclampsia. We will also assess whether aspirin dosing affects management of postpartum haemorrhage. Through this study, this international collaboration will generate critical evidence to align clinical guidelines globally on the optimal dose of aspirin for the prevention of pre-eclampsia.
The assessment of various national and international recommendations clearly indicates uncertainty around which dose is the safest and most efficacious in low-, middle- and high-income countries. Heterogeneity across risk screening and profile of trial populations, gestational age at recruitment, outcomes reported, different doses used and how the different doses are grouped in meta-analyses make it difficult to agree to a single recommended dose.
The need for a trial of 75 mg versus 150mg dose was identified as a research priority in the 2021 WHO recommendations. Since the evidence suggests that when compared to placebo, low dose aspirin of various doses between 50 to 182 mg /day reduce pre-eclampsia and is associated with as-yet-unquantified risk of haemorrhage, we ask the question: Is 150 mg/day aspirin more efficacious and sufficiently safe compared to 75 mg/day aspirin to make a definitive policy decision to use a higher dose? |
| Abstract of Study: | This study protocol describes formative research activities – the findings of these activities will be used to inform a multi-country randomized trial comparing two doses of aspirin to prevent pre-eclampsia in pregnant women at increased risk of developing pre-eclampsia. In this formative research, we aim to implement and optimise pre-eclampsia risk screening and clinical care of women at high-risk of pre-eclampsia, measure the baseline prevalence of key outcomes for the randomised trial, and identify potential barriers to the trial. |