Furosemide for Accelerated Recovery of Blood Pressure Postpartum

Study Overview
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Brief Summary
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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
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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.

Official Title
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Furosemide for Accelerated Recovery of Blood Pressure Postpartum

Conditions
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Hypertension, Pregnancy-Induced

Intervention / Treatment
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* Drug: Oral furosemide
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind, randomized, placebo control design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral furosemide<br>Oral furosemide 20 mg/day for a total of 5 consecutive doses. | Drug: Oral furosemide<br>* Furosemide (Lasix), 20 milligram, PO, PO, daily<br>|
| Placebo Comparator: Placebo Oral Tablet<br>Placebo once per day for a total of 5 consecutive doses. | Drug: Placebo Oral Tablet<br>* Placebo, PO, daily<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Furosemide, Postpartum, Hypertension