Clinical trial NCT03556761: Furosemide for Accelerated Recovery of Blood Pressure Postpartum
Official title: Furosemide for Accelerated Recovery of Blood Pressure Postpartum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension, Pregnancy-Induced
Keywords: Furosemide
Postpartum
Hypertension
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2018-06-14
Enrollment: 384
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind, randomized, placebo control design
Primary purpose: PREVENTION

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Persistently Elevated Blood Pressures 7 Days Postpartum
timeFrame: 0-7 days postpartum
measure: Time to Resolution
timeFrame: 0-14 days postpartum
Secondary outcomes:
measure: Postpartum Readmission
timeFrame: 0-6 weeks postpartum
measure: Number of Subjects Who Had Severe Hypertension Postpartum
timeFrame: 0-6 weeks postpartum
measure: Postpartum Length of Stay
timeFrame: 0-6 weeks postpartum
measure: Subjects With Complications During Hospitalization
timeFrame: 0-6 weeks postpartum
measure: Number of Subjects Experiencing One or More Adverse Effects
timeFrame: 0-6 weeks postpartum
measure: Number of Subjects That Required for Additional Antihypertensives
timeFrame: 0 to 6 weeks post-partum
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Lisa Levine, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.