This is a phase-III multi-center open-label randomized clinical trial of 4,120 individuals between 23 weeks, 0 days and 35 weeks, 6 days gestation with gestational hypertension or preeclampsia without severe features randomized to antihypertensive medication to a target blood pressure (BP) of \<140/90 mmHg or to no treatment for non-severe hypertension \< 160/110 mmHg (usual care). The primary endpoint is an adverse pregnancy composite comprised of preeclampsia with end-organ damage, medically indicated preterm delivery \<37 weeks 0 days gestation, fetal/neonatal/infant death, or placental abruption.
Singleton or di-chorionic twin gestation.
Gestational age at randomization from 23 weeks 0 days through 35 weeks 6 days based on clinical information and evaluation of the earliest ultrasound
Diagnosis of gestational hypertension or preeclampsia without severe features within 10 days prior to randomization.
Gestational hypertension or preeclampsia is defined as new onset systolic blood pressure 140-159 or diastolic blood pressure 90-109 (or both) on two occasions at least four hours apart on or after 20 weeks 0 days gestation with normal end-organ labs, with or without proteinuria.
Known allergy or hypersensitivity to both labetalol and nifedipine ER
Two blood pressure measurements ≥ 140/90 at least 4 hours apart prior to 20 weeks 0 days in the current pregnancy
Prescribed anti-HTN medication for the indication of lowering blood pressure within 12 months prior to conception or prior to 20 weeks 0 days in the current pregnancy. Use during a prior pregnancy and through 12 weeks postpartum, or use for stage 1 chronic hypertension is not an exclusion.
Current use of anti-HTN medication. Participants on anti-HTN medication for the purpose of treating non-severe hypertensive disorders of pregnancy, or for indications other than hypertension, who are willing to go through a 48 hour washout before randomization would be eligible.
Parallel
Anti-hypertensive medication titrated to a BP goal of <140/90 mmHg
DrugAntihypertensive medication titrated to a BP goal of \< 140/90 mmHg initiated on labetalol or nifedipine ER following standard dosing guidelines. For first line treatment with labetalol, 200 mg twice daily will be initiated and escalated to a BP goal of \<140/90 mmHg to a maximum dose of 2,400 mg/day (1,200 mg twice daily or 800 mg three times daily). If a maximum daily dose of 2,400 mg or maximal tolerated dose of labetalol is reached without achieving goal BP \<140/90 mmHg, or at provider discretion, nifedipine ER can be added as a second agent and titrated as per the nifedipine ER algorithm outlined below. For first line treatment with nifedipine ER, dosing will be initiated at 30 mg daily and escalated to a goal BP \<140/90 mmHg to a maximum dose of 120 mg/day (120 mg daily or 60 mg twice daily). If the maximum daily dose or maximal tolerated dose of nifedipine ER is reached without achieving goal BP \<140/90, or at provider discretion, labetalol can be added as described above.
Usual Care: Anti-hypertensive medication for BP ≥160/110 mmHg titrated to a goal of < 160/110 mmHg
Other interventionUsual care will not receive anti-hypertensive medication upon randomization. Participants will only be prescribed antihypertensive medication if their BP increases to ≥160/110 mmHg and titrated to a BP goal of \<160/110 mmHg. They will receive IV and/or oral anti-hypertensive medication as per local institutional protocols for management of severe range BP.
Number of participants with the adverse pregnancy composite
Number of participants with preeclampsia with severe features (excluding severe hypertension), medically indicated preterm birth less than 37 weeks 0 days, fetal or neonatal death, placental abruption.
Number of participants with the adverse perinatal composite outcome
Adverse perinatal composite defined as any one of the following: respiratory distress syndrome, 5-minute Apgar score less than or equal to 3, seizure, confirmed sepsis, Intraventricular hemorrhage (Grade 3-4), Bronchopulmonary dysplasia (Grade 3 or higher), necrotizing enterocolitis (Bell Stage greater than or equal to 2A), treated hyperbilirubinemia, treated hypoglycemia, hypoxic ischemic encephalopathy, fetal/neonatal/infant death
Number of participants with preeclampsia with severe features
Number of participants with preeclampsia with severe features defined using American College of Obstetricians and Gynecologists 2020 criteria through 6 weeks postpartum.
Number of perinatal deaths
Number of fetal or neonatal deaths through 28 days of life
Number of neonates who were small for gestational age <3rd percentile
Number of neonates who were small for gestational age (SGA) defined as a birth weight \<3rd and \<10th percentile for gestational age as defined by Aris et al.
Number of participants with adverse pregnancy composite by race/ethnicity
NIH-required analysis. Number of participants with preeclampsia with severe features (excluding severe hypertension), medically indicated preterm birth less than 37 weeks 0 days, fetal or neonatal death, placental abruption.
Click on the lead sponsor to view all of their trials.
The George Washington University Biostatistics Center
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
University of Alabama at Birmingham
Collaborator
University of Utah
Collaborator
Brown University
Collaborator
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