Lasix for the Prevention of De Novo Postpartum Hypertension

Phase 3

Completed

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

Interventions: Other: Placebo
Drug: Furosemide

Registration Number: NCT04752475

Lead Sponsor: Columbia University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 82

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Identical-appearing placebo, oral, once daily for 5 days
Lasix (furosemide)	Furosemide	Furosemide 20 mg, oral, once daily for 5 days

Primary Outcome Measures

Name	Time	Method
Mean Arterial Blood Pressure (MAP)	24 hours prior to discharge through discharge, up to 7 days	Difference in MAP averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation (whichever occurs first)

Secondary Outcome Measures

Name	Time	Method
Time to Discharge	Randomization through discharge, up to 7 days	Time until discharge from the hospital
Rate of de Novo Postpartum Preeclampsia	Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum	Number of participants who develop de novo postpartum hypertension. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Percent of Recorded Blood Pressures That Are Elevated	Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum	Percent of recorded blood pressures that are elevated (\>140 systolic OR \>90 diastolic).
Rate of Magnesium Sulfate Administration	Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum	Number of participants who receive intravenous magnesium sulfate for seizure prophylaxis. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Rate of Initiation of Antihypertensives	Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum	Number of participants receiving intravenous antihypertensive therapy and initiated on oral hypertensive therapy. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Rate of Severe Maternal Morbidity	Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum	Number of participants experiencing severe maternal morbidity (e.g. seizure, stroke, Posterior reversible encephalopathy syndrome (PRES), death, etc.) This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Rate of Triage or Emergency Department (ED) Presentation/Readmission	2 weeks postpartum, 6 weeks postpartum	Number of participants who experienced triage or ED presentation/readmission for hypertensive-related complaints. This outcome was assessed at 2 weeks postpartum and 6 weeks postpartum. Data is reported at 6 weeks postpartum.
Breastfeeding Continuation Rate	2 weeks postpartum, 6 weeks postpartum	Number of participants continuing to breastfeed of those who initiated breastfeeding after delivery. This outcome was assessed at Discharge (up to 7 days), 2 weeks postpartum, and 6 weeks postpartum. Data is reported at 2 weeks and 6 weeks postpartum.