Lasix for the Prevention of De Novo Postpartum Hypertension

Overview

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.

Full Title of Study: “Lasix for the Prevention of De Novo Postpartum Hypertension: A Randomized Controlled Trial (LAPP Trial)”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Prevention
  • Masking: Triple (Participant, Care Provider, Investigator)
• Study Primary Completion Date: April 18, 2022

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.

Interventions

• Drug: Furosemide
  • Furosemide 20 mg pill taken daily for 5 days
• Other: Placebo
  • Identical-appearing placebo pill taken daily for 5 days

Arms, Groups and Cohorts

• Experimental: Lasix (furosemide)
  • Furosemide 20 mg, oral, once daily for 5 days
• Placebo Comparator: Placebo
  • Identical-appearing placebo, oral, once daily for 5 days

Clinical Trial Outcome Measures

Primary Measures

• Mean arterial blood pressure (MAP)
  • Time Frame: 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 Measures

• Rate of de novo postpartum preeclampsia
  • Time Frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
  • Proportion of participants who develop de novo postpartum hypertension
• Frequency of hypertensive episodes
  • Time Frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
  • Mean frequency of recorded blood pressures that are elevated (>140 systolic OR >90 diastolic)
• Rate of magnesium sulfate administration
  • Time Frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
  • Proportion of participants who receive intravenous magnesium sulfate for seizure prophylaxis
• Rate of initiation of antihypertensives
  • Time Frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
  • Proportion of participants receiving intravenous antihypertensive therapy and initiated on oral hypertensive therapy
• Time to discharge
  • Time Frame: Randomization through discharge, up to 7 days
  • Time until discharge from the hospital
• Rate of severe maternal morbidity
  • Time Frame: Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum
  • Proportion of participants experiencing severe maternal morbidity (e.g. seizure, stroke, Posterior reversible encephalopathy syndrome (PRES), death, etc.)
• Frequency of triage or Emergency Department (ED) presentation/readmission
  • Time Frame: 2 weeks postpartum, 6 weeks postpartum
  • Mean frequency of triage or ED presentation/readmission for hypertensive-related complaints
• Breastfeeding continuation rate
  • Time Frame: 2 weeks postpartum, 6 weeks postpartum
  • Proportion of participants continuing to breastfeed of those who initiated breastfeeding after delivery

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Columbia University
• Provider of Information About this Clinical Study
  • Principal Investigator: Russell Miller, Sloane Hospital for Women Associate Professor of Prenatal Pediatrics (in Obstetrics and Gynecology) – Columbia University
• Overall Official(s)
  • Russell S. Miller, MD, Principal Investigator, Columbia University

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