PREPARE II trial protocol aims to assess sFlt-1/PlGF ratio and telemonitoring for reducing pre-eclampsia healthcare utilization

Pre-eclampsia is a severe hypertensive disorder of pregnancy, a leading cause of maternal and perinatal morbidity, driven by placental dysfunction and angiogenic imbalance. Current diagnostic and management strategies often lead to high rates of hospital admissions and outpatient visits. The sFlt-1/PlGF ratio has shown strong predictive characteristics for pre-eclampsia, but its impact on reducing healthcare utilization and overall costs remains unproven. This trial addresses the critical gap in understanding the real-world cost-effectiveness and clinical utility of integrating this biomarker with digital self-monitoring.

This is a randomized controlled trial protocol across six centers enrolling 470 women (≥16 years old) between 20 and 37 weeks of gestation with suspected pre-eclampsia due to one or more symptoms. Participants will be randomized to either standard care or an intervention arm. The intervention involves an algorithm based on the urine protein/creatinine ratio (PCr) and the sFlt-1/PlGF ratio, coupled with a telemonitoring strategy. The algorithm uses a PCr cut-off of 30 mg/mmol and an sFlt-1/PlGF ratio cut-off of 38 for risk stratification. Low-risk cases return to routine care, intermediate-risk receive telemonitoring, and high-risk require immediate admission. The primary endpoint is pre-eclampsia-related healthcare utilization in the first week post-testing.

As a trial protocol, no actual findings are reported; however, the power calculation for the study is based on specific hypotheses regarding the intervention's efficacy. The trial assumes that the integrated sFlt-1/PlGF ratio and telemonitoring strategy will lead to a significant de-escalation of care. Specifically, the intervention is hypothesized to reduce the frequency of pre-eclampsia-related hospital admissions and/or outpatient visits in the first week from 50% in the control group to 35% in the intervention group. This represents a 15% absolute reduction in healthcare utilization. The study is powered to detect this difference with 90% power and an alpha of 5%, accounting for a 5% loss to follow-up, requiring 235 women per arm. The risk stratification algorithm uses specific cut-offs: PCr of 30 mg/mmol and sFlt-1/PlGF ratio of 38 to guide clinical decisions, aiming to optimize resource allocation and patient management. This structured approach is designed to validate whether advanced biomarker testing can translate into tangible reductions in healthcare burden.

The trial hypothesizes a 15% absolute reduction in pre-eclampsia-related healthcare utilization in the first week, from 50% in controls to 35% in the intervention group.