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Postpartum Management of Gestational Hypertensive Disorders Using Furosemide

Postpartum Management of Gestational Hypertensive Disorders Using Furosemide: A Randomized Controlled Trial

Status
Terminated
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04343235
Enrollment
13
Registered
2020-04-13
Start date
2020-05-01
Completion date
2022-06-30
Last updated
2023-10-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension, Pregnancy-Induced

Keywords

pregnancy induced hypertension, preeclampsia, furosemide

Brief summary

* The main purpose of this study is to learn if incorporating a loop diuretic such as furosemide along with labetalol in the routine management of postpartum gestational hypertensive disorders could lower the need for additional anti-hypertensive agents to control blood pressures, improve blood pressures (as measured by systolic blood pressure, diastolic blood pressure and mean arterial blood pressures), shorten hospital stays and decrease readmissions for patients with gestational hypertensive disorders. * Based on a study by Veena et al1, there is reason to believe that the addition of furosemide to other anti-hypertensives may help decrease the need to add or increase the dose of medication to control blood pressures. There may be potential to shorten hospital stays and decrease readmissions, as well. Collecting data will be done using a prospective, randomized 1:1 controlled study assigning postpartum patients with a gestational hypertensive diagnosis to either labetalol alone or labetalol plus furosemide. * The study will be performed in the postpartum wing of Miami Valley Hospital Main Campus and would use patients who have consented to participate in the study with enrollees coming from the OB Staff population.

Detailed description

Background and Literature Review * There have been four documented studies investigating loop diuretics in the management of postpartum hypertensive disorders- Matthews et al2, Ascarelli et al3, Amorim et al4, and Veena et al. Of these studies, only Amorim and Veena were able to show statistical significance on any parameters. Amorim was able to show that there was an improvement of SBP, DBP and MAP, but the research was only presented as an abstract at a conference and not published, thereby making it impossible to draw any conclusions or practice guidelines. Veena demonstrated that by using furosemide and nifedipine in combination, the need for additional antihypertensive medication in severe pre-eclampsia in the postpartum period was reduced when compared to nifedipine alone. * A systematic review5 of postpartum hypertensive disorder management suggested that there was insufficient data to recommend any single pharmacological intervention at this time in the management of gestational hypertensive disorders. The review emphasized the need for further studies to be conducted to help guide management of patients affected by gestational hypertensive disorders in the future. Objectives ● Main Question * Does the use of furosemide plus labetalol improve blood pressures in the postpartum period of patients with gestational hypertensive disorders versus labetalol alone? * Primary ■ Will there be a requirement to escalate antihypertensive therapy to control blood pressures * Secondary * Improvement of gestational hypertensive disorders by measurement of systolic blood pressure, diastolic blood pressure and mean arterial pressure * Shortened hospital stay in patients with hypertensive disorders * Breastfeeding status at 1 week postpartum visit in mothers planning to breastfeed * Readmission for postpartum hypertensive disorders Significance to patient, institution, and profession * As a referral center and being the region's leader, Miami Valley is very accustomed to accepting transfers of high acuity patients often times with hypertensive disorders being the root cause of the transport * The majority of the OB staff population being served at Miami Valley Hospital is African American. According to Myatt6, the incidence of pre-eclampsia in the African American population is greater than double the Caucasian population (11% to 5%) thereby making this study very applicable to the patient population served at Miami Valley Hospital. * With the construct of the study, costs abe kept low by utilizing already established resources and practices (blood pressure cuffs, nurses, routine one week blood pressure checks) while only adding on the unit cost of furosemide. * If treatment with labetalol and furosemide is found to be useful, it would be not only a very inexpensive, cost effective way of improving patient outcomes and possibly decreasing lengths of stay stateside, but in improving global practice in places that are lacking in resources privy to first world countries. Methods * The study would be designed as: * A prospective randomized 1:1 controlled trial including postpartum women with gestational hypertension or preeclampsia * Patients with chronic hypertension would be excluded from the study * One arm receiving 200mg labetalol BID alone on PPD#1 or 24 hours after magnesium sulfate * One arm receiving 200mg labetalol BID and a five day course of furosemide 20mg QD on PPD#1 or 24 hours after magnesium sulfate * Recording any occurrence when an increased amount of labetalol is needed to maintain blood pressures below 150 SBP and/or 100 DBP per ACOG recommendations.7 ■ In the event of persistently elevated blood pressures, labetalol will be increased to 400mg TID and escalated to 600mg TID and finally 800mg TID as indicated * Measurement of blood pressure every four hours after administration until patient discharge * Measurement of urine output every 12 hours until discharge * Compare average systolic, diastolic and mean arterial pressures between the two groups during admission and at one week postpartum * Data will be collected using the OB Staff population at Miami Valley Hospital Main Campus. * The research will be analyzed and interpreted by the research team conducting the study. * Potential difficulties and limitations include compliance concerns of mandatory one week blood pressure follow up appointment. * Using the Veena et al paper as a frame of reference, a sample size of 140 divided evenly across the two treatment arms would achieve statistical significance in determining the need to escalate anti-hypertensive therapy. * The unit cost of one tablet of labetalol 200mg and furosemide 20mg is currently $0.32 and $1.23, respectively. 8,9 * The study would use already readily available automated blood pressure cuff machines on the postpartum wing.

Interventions

DRUGfurosemide

five day course of furosemide 20mg QD

DRUGlabetalol

200mg labetalol BID

Sponsors

Wright State University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Masking description

randomized open label

Intervention model description

Randomized controlled trial

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No

Inclusion criteria

* Postpartum women delivering at Miami Valley Hospital * Diagnosis of gestational hypertension or preeclampsia * Able to provide written informed consent

Exclusion criteria

* Diagnosis of chronic hypertension * Allergy to study medications * Unable to understand English

Design outcomes

Primary

MeasureTime frameDescription
Change of Dose for Antihypertensive TherapyChange in dose of hypertensive therapy from randomization until hospital discharge (up to 7 days)number of patients who require a change in the dose of labetalol to control BP

Secondary

MeasureTime frameDescription
Change of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)Average mean arterial pressure on Day 0, Day 1, and Day 2average mean arterial pressure reading on Day 0, Day 1, and Day 2
Change of Gestational Hypertensive Disorder Symptoms (Diastolic BP)Average diastolic blood pressure on Day 0, Day 1, and Day 2average diastolic blood pressure reading on Day 0, Day 1, and Day 2
Change of Gestational Hypertensive Disorder Symptoms (Systolic BP)Average systolic blood pressure for Day 0, Day 1, and Day 2average systolic blood pressure reading on Day 0, Day 1, and Day 2
Breastfeeding Statusat 1 week postpartum visitbreastfeeding continuation after discharge
Hospital Readmissionup to 14 days after dischargereadmission for hypertension management
Hospital Length of StayNumber of days of hospital stay from randomization to dischargedays in hospital after delivery

Countries

United States

Participant flow

Participants by arm

ArmCount
Labetalol + Furosemide
labetalol + furosemide furosemide: five day course of furosemide 20mg QD labetalol: 200mg labetalol BID
6
Labetalol Only
labetalol only labetalol: 200mg labetalol BID
7
Total13

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyLost to Follow-up32

Baseline characteristics

CharacteristicLabetalol + FurosemideLabetalol OnlyTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
6 Participants7 Participants13 Participants
Age, Continuous28.0 years
STANDARD_DEVIATION 2.7
27.0 years
STANDARD_DEVIATION 5.4
27.5 years
STANDARD_DEVIATION 4.3
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants1 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants6 Participants12 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
3 Participants3 Participants6 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
3 Participants4 Participants7 Participants
Region of Enrollment
United States
6 participants7 participants13 participants
Sex: Female, Male
Female
6 Participants7 Participants13 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 60 / 7
other
Total, other adverse events
0 / 60 / 7
serious
Total, serious adverse events
0 / 60 / 7

Outcome results

Primary

Change of Dose for Antihypertensive Therapy

number of patients who require a change in the dose of labetalol to control BP

Time frame: Change in dose of hypertensive therapy from randomization until hospital discharge (up to 7 days)

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Labetalol + FurosemideChange of Dose for Antihypertensive Therapy3 Participants
Labetalol OnlyChange of Dose for Antihypertensive Therapy0 Participants
p-value: 0.21Fisher Exact
Secondary

Breastfeeding Status

breastfeeding continuation after discharge

Time frame: at 1 week postpartum visit

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Labetalol + FurosemideBreastfeeding Status1 Participants
Labetalol OnlyBreastfeeding Status3 Participants
p-value: 0.57Fisher Exact
Secondary

Change of Gestational Hypertensive Disorder Symptoms (Diastolic BP)

average diastolic blood pressure reading on Day 0, Day 1, and Day 2

Time frame: Average diastolic blood pressure on Day 0, Day 1, and Day 2

ArmMeasureGroupValue (MEAN)Dispersion
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Diastolic BP)Day 084.1 mm of mercuryStandard Deviation 11.8
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Diastolic BP)Day 181.8 mm of mercuryStandard Deviation 4.5
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Diastolic BP)Day 278.8 mm of mercuryStandard Deviation 7.1
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Diastolic BP)Day 080.1 mm of mercuryStandard Deviation 10.4
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Diastolic BP)Day 180.7 mm of mercuryStandard Deviation 8.4
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Diastolic BP)Day 275.5 mm of mercuryStandard Deviation 7.9
p-value: 0.54ANOVA
Secondary

Change of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)

average mean arterial pressure reading on Day 0, Day 1, and Day 2

Time frame: Average mean arterial pressure on Day 0, Day 1, and Day 2

ArmMeasureGroupValue (MEAN)Dispersion
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)Day 298.0 mm of mercuryStandard Deviation 8.7
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)Day 0102.4 mm of mercuryStandard Deviation 10.7
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)Day 199.5 mm of mercuryStandard Deviation 4.7
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)Day 296.0 mm of mercuryStandard Deviation 6.3
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)Day 0100.0 mm of mercuryStandard Deviation 9.2
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)Day 1100.1 mm of mercuryStandard Deviation 7.7
p-value: 0.77ANOVA
Secondary

Change of Gestational Hypertensive Disorder Symptoms (Systolic BP)

average systolic blood pressure reading on Day 0, Day 1, and Day 2

Time frame: Average systolic blood pressure for Day 0, Day 1, and Day 2

ArmMeasureGroupValue (MEAN)Dispersion
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Systolic BP)Day 0138.4 mm of mercuryStandard Deviation 11.2
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Systolic BP)Day 1134.9 mm of mercuryStandard Deviation 5.4
Labetalol + FurosemideChange of Gestational Hypertensive Disorder Symptoms (Systolic BP)Day 2135.2 mm of mercuryStandard Deviation 13.7
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Systolic BP)Day 0138.1 mm of mercuryStandard Deviation 9.4
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Systolic BP)Day 1138.2 mm of mercuryStandard Deviation 8.5
Labetalol OnlyChange of Gestational Hypertensive Disorder Symptoms (Systolic BP)Day 2136.7 mm of mercuryStandard Deviation 6
p-value: 0.7ANOVA
Secondary

Hospital Length of Stay

days in hospital after delivery

Time frame: Number of days of hospital stay from randomization to discharge

ArmMeasureValue (MEAN)Dispersion
Labetalol + FurosemideHospital Length of Stay3.5 daysStandard Deviation 1.3
Labetalol OnlyHospital Length of Stay4.3 daysStandard Deviation 1.8
p-value: 0.4795% CI: [-1.5, 3.1]t-test, 2 sided
Secondary

Hospital Readmission

readmission for hypertension management

Time frame: up to 14 days after discharge

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Labetalol + FurosemideHospital Readmission1 Participants
Labetalol OnlyHospital Readmission2 Participants
p-value: >0.99Fisher Exact

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026