Lasix for the Prevention of De Novo Postpartum Hypertension

Study Overview
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Brief Summary
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Primary objective: To evaluate whether oral furosemide can help prevent de novo postpartum hypertension (new-onset high blood pressure after delivery) by reducing blood pressure after delivery in high-risk women. Secondary objectives: To evaluate whether oral furosemide administered to high-risk women after delivery can reduce the frequency of postpartum hypertensive episodes, the need for antihypertensive therapy, the risk of postpartum preeclampsia, and the incidence of severe maternal morbidity.

Detailed Description
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Hypertensive disorders of pregnancy are one of the leading causes of maternal morbidity and mortality worldwide. The majority of clinical research has focused on pregnancy-related hypertension that develops in the antenatal period, while studies of the incidence, risk factors, and prevention of postpartum hypertension are limited. In particular, there is a paucity of data about the clinical entity known as de novo postpartum hypertension, in which women who are normotensive throughout pregnancy and delivery subsequently go on to develop high blood pressure in the immediate to late postpartum period. Of those with postpartum preeclampsia, 33-69% were normotensive antepartum. Early identification and treatment of antepartum preeclampsia has been shown to decrease some severe maternal outcomes. Conversely, women with de novo postpartum hypertensive disorders remain among the highest risk for severe maternal morbidity due to decreased surveillance and lack of data regarding preventive therapies and interventions. Evidence from multiple randomized controlled trials have demonstrated a benefit in the use of oral loop-diuretics in decreasing postpartum systolic blood pressure, promoting faster normalization of blood pressure, and decreasing the need for antihypertensive therapy in women with an antenatal diagnosis of preeclampsia. Biological plausibility suggests that loop-diuretic therapy may similarly mitigate the normal physiologic mechanism that has been implicated in the pathogenesis of hypertensive complications after delivery in women at risk for de novo postpartum hypertension. This study is a double-blind randomized placebo-controlled trial of 82 high-risk women to assess whether treatment with oral Lasix (furosemide) after delivery reduces blood pressure at the time of discharge. Women at high risk for de novo postpartum hypertension will be randomized to a five-day course of either 20 mg oral Lasix (furosemide) or placebo once daily initiated after delivery. Women will be monitored through their routine 2-week and 6-week postpartum visits, during which times hypertensive complications and adverse effects of therapy will be assessed.

Official Title
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Lasix for the Prevention of De Novo Postpartum Hypertension: A Randomized Controlled Trial (LAPP Trial)

Conditions
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Postpartum Pregnancy-Induced Hypertension, Postpartum Preeclampsia, Hypertension, Pregnancy-Induced, Hypertension

Intervention / Treatment
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* Drug: Furosemide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postpartum women No antenatal diagnosis of hypertensive disorder of pregnancy at the time of admission for delivery, defined as existing chronic hypertension diagnosis or documented blood pressure of ≥140 systolic OR ≥90 diastolic on at least 2 occasions at least 4 hours apart prior to delivery admission who do not go on to get magnesium for seizure prophylaxis by the time of delivery At least 18 years of age English or Spanish speakers One or more high risk factors for development of de novo postpartum hypertension Exclusion Criteria: Non-English or Spanish speakers Women with a contraindication to diuretic therapy Women who have used diuretics in the two weeks prior to delivery

Ages Eligible for Study
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Minimum Age: 18 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: The study is a randomized controlled clinical trial of 82 women with one or more high-risk factors for de novo postpartum hypertension, randomized to one of two arms: 20 mg PO Lasix (furosemide) daily for 5 days or identical-appearing daily placebo for 5 days.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lasix (furosemide)<br>Furosemide 20 mg, oral, once daily for 5 days | Drug: Furosemide<br>* Furosemide 20 mg pill taken daily for 5 days<br>* Other names: Lasix;|
| Placebo Comparator: Placebo<br>Identical-appearing placebo, oral, once daily for 5 days | Other: Placebo<br>* Identical-appearing placebo pill taken daily for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Arterial Blood Pressure (MAP) | Difference in MAP averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation (whichever occurs first) | 24 hours prior to discharge through discharge, up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of de Novo Postpartum Preeclampsia | Proportion of participants who develop de novo postpartum hypertension | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | 
| Frequency of Hypertensive Episodes | Mean frequency of recorded blood pressures that are elevated (>140 systolic OR >90 diastolic) | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | 
| Rate of Magnesium Sulfate Administration | Proportion of participants who receive intravenous magnesium sulfate for seizure prophylaxis | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | 
| Rate of Initiation of Antihypertensives | Proportion of participants receiving intravenous antihypertensive therapy and initiated on oral hypertensive therapy | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | 
| Time to Discharge | Time until discharge from the hospital | Randomization through discharge, up to 7 days | 
| Rate of Severe Maternal Morbidity | Proportion of participants experiencing severe maternal morbidity (e.g. seizure, stroke, Posterior reversible encephalopathy syndrome (PRES), death, etc.) | Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum | 
| Frequency of Triage or Emergency Department (ED) Presentation/Readmission | Mean frequency of triage or ED presentation/readmission for hypertensive-related complaints | 2 weeks postpartum, 6 weeks postpartum | 
| Breastfeeding Continuation Rate | Proportion of participants continuing to breastfeed of those who initiated breastfeeding after delivery | 2 weeks postpartum, 6 weeks postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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De novo postpartum hypertension, New-onset postpartum hypertension, Lasix, Furosemide