Testing the use of a biomarker (PlGF) to evaluate superimposed preeclampsia in pregnant women with chronic hypertension (B.I.P.E.S.): a randomized clinical trial study protocol

Placental growth factor (PlGF) is a promising biomarker for differential diagnosis between worsening chronic hypertension (CH) and superimposed preeclampsia (SPE) after 20 weeks of gestation. The aim of this study is to compare maternal and perinatal outcomes and costs in suspected cases of SPE, evaluated with and without the use of PlGF, for clinical management in women with CH. Randomized Clinical Trial (RCT). Pregnant women with CH and suspected SPE (due to worsening blood pressure control, excessive weight gain, onset or worsening of proteinuria, or signs of placental insufficiency after 20 weeks of gestation) will be eligible. Exclusion criteria: diagnosis of severe disease (HELLP syndrome, eclampsia, signs of imminent eclampsia, hypertensive crisis, or acute fetal distress). The calculated sample size is 140 women with an estimated inclusion period of 12 months. Eligible women will be invited to participate and will be randomly selected for standard follow-up or intervention (rapid PlGF test) in addition to the routine laboratory protocol for investigating SPE. The test result will be made available to the healthcare professionals within 30 min. When PlGF is considered normal (value ≥ 100 pg/ml), woman will be discharged for outpatient follow-up scheduled in 7 or 14 days (depending on gestational age (GA)). Cases with abnormal PlGF (between 12 and 100 pg/ml) will be evaluated as probable SPE, with hospitalization or early follow-up, and cases with suggestive severe placental insufficiency (PlGF < 12 pg/ml) will be hospitalized for strict maternal–fetal surveillance. Primary outcome will be the frequency of preterm childbirth. Maternal and perinatal outcomes, length of hospital stay, outpatient follow-up visits, serial collection of exams and costs of suspected cases of SPE, with and without the use of the rapid PlGF test (Quidel-Triage) will be compared. The use of PlGF may contribute to better distinguishing between SPE and CH and therefore avoiding medically indicated preterm delivery and other surveillance interventions during follow-up. This protocol was registered on REBEC (The Brazilian Registry of Clinical Trials) platform under the code RBR-2zx5y9r in 07/09/2024.