Labetalol or Nifedipine for Control of Postpartum Hypertension: A Randomized Controlled Trial

Randomized trial comparing risk of hospital readmission and hypertensive complications between patients managed on Labetalol compared to Nifedipine.

Study Overview

• Status: Recruiting
• Conditions: Hypertension in Pregnancy; Postpartum Preeclampsia
• Intervention / Treatment: Drug: NIFEdipine ER; Drug: Labetalol Oral Tablet

Detailed Description

Enrollment:

Patients will be identified daily using an EMR screening tool. Those that meet inclusion criteria will then be approached by the investigators or research RN for enrollment. Patients consenting to be involved in the study will then be randomly assigned to the nifedipine or labetalol arms of the study. Block randomization will be performed in blocks of 50 with goal of 600 total patients (300 in each arm).

Treatment Protocols

Nifedipine Study Arm:

Patients randomized to Nifedipine will be started on Nifedipine XR 30mg BID. Escalation in therapy to be determined by primary provider. Maximum dose of Nifedipine is 120mg daily. All patients will be monitored for signs and symptoms of hypotension or medication side effect- severe HA, orthostasis, syncope. Patients with further hypertension will then be started on Labetalol as a second agent at 200mg TID and escalated as needed with the goal of being normotensive for at least 12 hours before discharge. Patients will not be kept hospitalized for purposes of the study.

Labetalol Study Arm:

Patients randomized to Labetalol will be started on 200mg TID. Escalation in therapy to be determined by primary provider. Maximum dose is 2400mg in a day. All patients will be monitored for signs and symptoms of hypotension or medication side effect- orthostasis, syncope, bradycardia. Patient's that reach 800mg TID or cannot escalate therapy due to bradycardia will then be started on Nifedipine 30mg BID and escalated as needed with the goal of normotension for at least 12 hours before discharge. Patients will not be kept hospitalized for purposes of the study.

All Patients:

Outpatient follow up to be dictated by the discharging provider. Patients will be called at 6 months to determine if they were readmitted and their MRN will be used to query the EMR for readmission or ER evaluation.

Power Calculation Anticipated incidence in Nifedipine arm is 1%. Pilot study indicated a readmission risk of 0.2% in patients discharge normotensive on nifedipine. We anticipate this will be higher as some patients will likely be discharged with HTN. Anticipated incidence in the Labetalol arm is 7%. This number was based on a 5.8% risk of readmission in the normotensive group and 12.6% in the hypertensive group. As with the nifedipine arm, we anticipate there will be some patients discharged hypertensive increasing this risk above that of patients discharged normotensive.

With alpha set at 0.05 and power of 80%, we anticipate we will need at least 332 total patients, 166 in each arm. The original pilot data included patients with both physician identified hypertensive disease as well as those patients only identified by the EMR screening tool. Those patients identified by the screening tool had an increased risk of readmission compared to the overall population based risk of readmission (3.6% vs 1%). Their risk is lower than those patients identified by their provider 5.2%. Our plan is to enroll 600 patients, 300 in each arm as some patients will require multiple medications and due to the dilution of including a lower risk group we feel the initial power calculation does not take these factors into account. All data will be analyzed by intention to treat and crossover between groups for side effects or primary physician change in management will be reported/monitored.

Data Safety Monitoring Data will be reviewed q 6 months for statistical significance once at least 100 patients have been enrolled in each arm. If the effect is statistically significant to a p of 0.05 the study will be terminated for safety reasons. The DSMB will also monitor patient crossover and medication side effects as part of their evaluation. Data safety monitoring board will be comprised of 2 maternal fetal medicine physicians, 1 general obstetrician and the study research RN. Data will be analyzed as each block in the randomization is completed.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Todd Lovgren, MD; Phone Number: 4028151970; Email: todd.lovgren@nmhs.org
• Study Contact Backup: Name: Joshua Dahlke, MD; Phone Number: 4028151970; Email: joshua.dahlke@nmhs.org

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68022
      • Recruiting
      • Nebraska Methodist Women's Hospital
      • Contact: Todd Lovgren; Phone Number: 402-815-1970; Email: todd.lovgren@nmhs.org
      • Contact: Josh Dahlke; Phone Number: 4028151970; Email: joshua.dahlke@nmhs.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Any patient admitted for delivery by cesarean or vaginal delivery at 24 weeks gestation or greater with hypertension(HTN). Hypertension will be defined during the study as either a systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg on two occasions at least 4 hours apart. This definition is consistent with the ACOG definition for pregnancy related HTN. Following enrollment, treatment will be escalated at discretion of primary provider with the goal of normotension.

Exclusion Criteria:

History of moderate persistent asthma, coronary artery disease, heart failure, AV heart block, pulmonary edema

• Contraindication to either Nifedipine or Labetalol
• HR <60 or >110
• Native language other than English or Spanish

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
Active Comparator: Nifedipine; Patients randomized to Nifedipine will be started on Nifedipine XR 30mg BID. Escalation in therapy to be determined by primary provider. Maximum dose of Nifedipine is 120mg daily. All patients will be monitored for signs and symptoms of hypotension or medication side effect- severe HA, orthostasis, syncope.	Drug: NIFEdipine ER; See Nifedipine arm.; Other Names: Procardia XL
Active Comparator: Labetalol; Patients randomized to Labetalol will be started on 200mg TID. Escalation in therapy to be determined by primary provider. Maximum dose is 2400mg in a day. All patients will be monitored for signs and symptoms of hypotension or medication side effect- orthostasis, syncope, bradycardia.	Drug: Labetalol Oral Tablet; See Labetalol arm.; Other Names: Trandate; Normodyne

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Readmission	Patients will be monitored following delivery for readmission to the hospital. To improve patient capture, all patients will be called at 6 months to identify complications or if hospital admission occured in the 6 months following delivery	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication failure	Need for additional antihypertensive medication	Any time during the 6 months following delivery
Medication change or discontinuation	Need to change medication or discontinue medication due to side effects or complications of medication.	Any time during the 6 months following delivery

Collaborators and Investigators

• Sponsor: Nebraska Methodist Health System
• Investigators: Principal Investigator: Todd Lovgren, MD, Nebraska Methodist Health System

Publications and helpful links

General Publications

• Lovgren T, Connealy B, Yao R, Dahlke JD. Postpartum management of hypertension and effect on readmission rates. Am J Obstet Gynecol MFM. 2022 Jan;4(1):100517. doi: 10.1016/j.ajogmf.2021.100517. Epub 2021 Oct 30.
• Lovgren T, Connealy B, Yao R, D Dahlke J. Postpartum medical management of hypertension and risk of readmission for hypertensive complications. J Hypertens. 2023 Feb 1;41(2):351-355. doi: 10.1097/HJH.0000000000003340. Epub 2022 Dec 13.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hypertension; Pregnancy; Postpartum; Labetalol; Preeclampsia; Nifedipine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Sympathomimetics; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Nifedipine; Labetalol
• Other Study ID Numbers: NebraskaMethodistHS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Yes, deidentified data will be shared on a case by case basis.
• IPD Sharing Time Frame: On completion of study for 12 months.
• IPD Sharing Access Criteria: TBD by primary author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes