Nifedipine and Enalapril vs Nifedipine and Labetalol for the Treatment of Postpartum Hypertension Study (NEPHRON)

Nifedipine and Enalapril vs Nifedipine and Labetalol for the Treatment of Postpartum Hypertension Study (NEPHRON)

To determine if nifedipine and enalapril will have better blood pressure control in the postpartum setting compared to nifedipine and labetalol.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension; Postpartum Preeclampsia
• Intervention / Treatment: Drug: Nifedipine and Enalapril; Drug: Nifedipine and Labetalol

Detailed Description

The primary objective is to assess the efficacy of enalapril on hypertension as a second line agent compared to labetalol in the postpartum period. This is a pragmatic, unblinded, randomized trial of postnatal patients with hypertension who are on nifedipine postpartum and require a second oral agent. Patients will be evaluated for eligibility and consented when they require initiation of a single oral antihypertension agent, if they require IV antihypertensive therapy, or if they are on a single oral antihypertensive medication intrapartum. After consenting for the study, patients will be initiated on extended release nifedipine 30 mg daily as the primary drug for treatment and increased to a maximum dose of 60 mg twice daily prior to starting a second agent. Nifedipine was chosen as the universal first line agent due to its longevity and diuretic properties. Medication up titration and initiation of a second antihypertensive agent will occur at the discretion of the treatment team. Medication adjustments are recommended when the majority (>50%) of recorded blood pressures are greater than 140 mm Hg systolic or 90 mm Hg diastolic during a 24-hour time period. This threshold was chosen based on our knowledge that higher systolic blood pressures are associated with increased cardiovascular outcomes. Women requiring an additional medication for treatment of hypertension will be randomly assigned to receive enalapril 5 mg twice daily or labetalol 200 mg twice daily for concomitant therapy.

Blood pressures will be analyzed at 24 hours after initiation of a second oral agent, 3 days following hospital discharge, 2 weeks postpartum and 6 weeks postpartum. Need for IV antihypertensive agents and an additional third oral agent will be reviewed. As per standard of care, participants will be asked to monitor their blood pressure (BP) at home twice daily and keep their own blood pressure log to share with their outpatient provider. Patients are instructed to notify their outpatient provider of elevated blood pressure readings according to the Postpartum Hypertension Information Sheet that will be provided to all study participants.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amol Malshe, M.D.; Phone Number: 216 903-9646; Email: malshea@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Postpartum women aged 18 years or older
• Clinical diagnosis of hypertensive disorder in pregnancy (gestational hypertension, chronic hypertension, preeclampsia with or without severe features)
• Taking Nifedipine 60 mg every 12 hours for blood pressure control
• Persistently elevated blood pressure at/above 140/90 mmHg in a 24-hour time period or have one or more severe range blood pressure at/above 160/110 mmHg requiring a second antihypertensive medication
• English speaking

Exclusion Criteria:

• Taking ≥2 antihypertensive agents during pregnancy
• Heart block
• Heart rate <60 or >120 beats per minute
• Heart failure
• Creatinine >1.5 mg/dL
• Renal artery stenosis
• Active connective tissue disease
• Cerebrovascular accident
• Failed treatment or contraindications to nifedipine, enalapril or labetalol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nifedipine and Enalapril; Nifedipine 60mg by mouth every twelve hours plus Enalapril 5mg by mouth every twelve hours	Drug: Nifedipine and Enalapril; Nifedipine 60mg by mouth every twelve hours plus Enalapril 5mg by mouth every twelve hours; Other Names: Procardia and Vasotec
Active Comparator: Nifedipine and Labetalol; Nifedipine 60mg by mouth every twelve hours plus Labetalol 200mg by mouth every twelve hours	Drug: Nifedipine and Labetalol; Nifedipine 60mg by mouth every twelve hours plus Labetalol 200mg by mouth every twelve hours; Other Names: Procardia and Trandete

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite postpartum hypertension treatment failure within 6 weeks postpartum	The primary outcome is a binary composite outcome, defined as the occurrence of any one or more of the following events within 6 weeks postpartum: Prolonged hospitalization, Hospital readmission for hypertension, Persistence of hypertension beyond 14 days postpartum, Requirement for acute treatment of severe-range hypertension. Participants experiencing at least one component will be classified as having met the composite outcome.	6-weeks postpartum

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Amol Malshe, M.D., The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amides; Amines; Alcohols; Amino Alcohols; Ethanolamines; Dihydropyridines; Dipeptides; Salicylamides; Nifedipine; Enalapril; Labetalol; Enalaprilat
• Other Study ID Numbers: 24-918

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No