Furosemide for Accelerated Recovery of Blood Pressure Postpartum (ForBP)

A randomized, double-blind, placebo-controlled single center investigation of furosemide's effect on postpartum blood pressure control in pregnancies affected by hypertensive disorders of pregnancy

Study Overview

• Status: Completed
• Conditions: Hypertension, Pregnancy-Induced
• Intervention / Treatment: Drug: Oral furosemide; Drug: Placebo Oral Tablet

Detailed Description

Hypertensive disorders of pregnancy are recognized causes of significant maternal/fetal morbidity and mortality, accounting for approximately 18% of maternal deaths worldwide. While significant research has been done on the evaluation and management of hypertension during pregnancy, studies of postpartum hypertension (PPHTN) are usually limited by their retrospective design and focus on inpatients in the immediate postpartum period (2-6 days), or patients who were readmitted due to complications related to hypertension. Few studies have investigated the incidence and proper management of hypertension in the postpartum period. Furthermore, in the United Kingdom, a review of maternal deaths determined that 10% were related to hypertensive disorders in pregnancy (HDP) in the postpartum period. Postpartum hypertension is also the cause of approximately 27% of readmissions to the hospital. These studies clearly show that PPHTN is associated with significant morbidity and that it is important to develop interventions that can reduce its effects.

In patients with HDP, postpartum blood pressure has been shown to decrease in the first 48 hours postpartum only to then increase in days 3-6 postpartum. This phenomenon is thought to be secondary to large fluid shifts, both secondary from fluid retention during the pregnant state as well as from fluids given intrapartum. Furthermore, large volumes of sodium are also mobilized into the intravascular compartment at this time. Given the latter, furosemide, a loop diuretic that mobilizes sodium and fluid excretion has been posed as a method to prevent severe range blood pressures and their associated maternal morbidity in the postpartum period.

• Study Type: Interventional
• Enrollment (Actual): 384
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Hypertensive disorder of pregnancy diagnosed antepartum or intrapartum
• Gestational hypertension
• Pre-eclampsia with or without severe features
• Superimposed pre-eclampsia with or without severe features
• New diagnosis of HDP within 24 hours from delivery
• Postpartum, delivery ≥ 20 weeks estimated gestational age
• Age ≥18 years old

Exclusion Criteria:

• History of allergic reaction to furosemide
• High risk comorbidities for which treatment may be indicated or contraindicated: class C or higher diabetes mellitus, chronic kidney disease or baseline creatinine >1.2, cardiac disorders including cardiomyopathy, congenital heart disease, angina or coronary heart disease, rheumatic disease (lupus), sickle cell disease
• Baseline labs with K <3
• Use of furosemide or other diuretics antepartum or intrapartum
• Use of ototoxic agents including aminoglycosides (ie, Gentamicin for >1 dose), cephalosporins (ie Ancef >1 dose),
• Patient unstable for protocol per investigator's judgement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Oral furosemide; Oral furosemide 20 mg/day for a total of 5 consecutive doses.	Drug: Oral furosemide; Furosemide (Lasix), 20 milligram, PO, PO, daily
PLACEBO_COMPARATOR: Placebo Oral Tablet; Placebo once per day for a total of 5 consecutive doses.	Drug: Placebo Oral Tablet; Placebo, PO, daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistently Elevated Blood Pressures 7 Days Postpartum	To compare the rate of persistently elevated blood pressures (>140/90) in women that receive a five day furosemide course compared to those that receive placebo.	0-7 days postpartum
Time to Resolution	To compare the time (days) required to achieve a resolution of elevated blood pressure, adjusted for mode of delivery.	0-14 days postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postpartum Readmission	Number of subjects with one or more readmission/ER visit that were hypertension related	0-6 weeks postpartum
Number of Subjects Who Had Severe Hypertension Postpartum	Number of women who had severe hypertension (systolic blood pressure>160 millimeters of mercury or diastolic blood pressure>110 millimeters of mercury) postpartum	0-6 weeks postpartum
Postpartum Length of Stay	Number of days postpartum participants stayed in the hospital	0-6 weeks postpartum
Subjects With Complications During Hospitalization	Subjects with complications during hospitalization related to hypertensive disorders of pregnancy.	0-6 weeks postpartum
Number of Subjects Experiencing One or More Adverse Effects	Number of subjects experiencing one or more adverse effects secondary to furosemide	0-6 weeks postpartum
Number of Subjects That Required for Additional Antihypertensives	Number of subjects that required additional hypertensive medication after discharge	0 to 6 weeks post-partum

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Lisa Levine, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Lopes Perdigao J, Lewey J, Hirshberg A, Koelper N, Srinivas SK, Elovitz MA, Levine LD. Furosemide for Accelerated Recovery of Blood Pressure Postpartum in women with a hypertensive disorder of pregnancy: A Randomized Controlled Trial. Hypertension. 2021 May 5;77(5):1517-1524. doi: 10.1161/HYPERTENSIONAHA.120.16133. Epub 2021 Feb 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 20, 2018
• Primary Completion (ACTUAL): December 4, 2019
• Study Completion (ACTUAL): February 5, 2020

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (ACTUAL): June 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Hypertension; Postpartum; Furosemide
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Hypertension; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 829444

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