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

Hypertension in Pregnancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05309460
• Other study ID #: NebraskaMethodistHS
• Status: Recruiting
• Phase: Phase 4
• Start date: June 20, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: April 2024
• Source: Nebraska Methodist Health System
• Contact: Todd Lovgren, MD
• Phone: 4028151970
• Email: todd.lovgren[@]nmhs.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension in Pregnancy
• Hypertension, Pregnancy-Induced
• Postpartum Preeclampsia
• Pre-Eclampsia

Intervention

Drug:
• Labetalol Oral Tablet
See Labetalol arm.
• NIFEdipine ER
See Nifedipine arm.

Locations

Country	Name	City	State
United States	Nebraska Methodist Women's Hospital	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Nebraska Methodist Health System

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Medication failure	Need for additional antihypertensive medication	Any time during the 6 months following delivery
Secondary	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