Lasix for the Prevention of De Novo Postpartum Hypertension

Hypertension Clinical Trial

— LAPP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04752475
• Other study ID #: AAAT2525
• Status: Completed
• Phase: Phase 3
• Start date: October 20, 2021
• Est. completion date: May 28, 2022

Study information

• Verified date: April 2023
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: May 28, 2022
• Est. primary completion date: April 18, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pregnancy-Induced
• Postpartum Preeclampsia
• Postpartum Pregnancy-Induced Hypertension
• Pre-Eclampsia

Intervention

Drug:
• Furosemide
Furosemide 20 mg pill taken daily for 5 days

Other:
• Placebo
Identical-appearing placebo pill taken daily for 5 days

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

References & Publications (14)

ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019 Jan;133(1):1. doi: 10.1097/AOG.0000000000003018. — View Citation

Al-Safi Z, Imudia AN, Filetti LC, Hobson DT, Bahado-Singh RO, Awonuga AO. Delayed postpartum preeclampsia and eclampsia: demographics, clinical course, and complications. Obstet Gynecol. 2011 Nov;118(5):1102-1107. doi: 10.1097/AOG.0b013e318231934c. — View Citation

Ascarelli MH, Johnson V, McCreary H, Cushman J, May WL, Martin JN Jr. Postpartum preeclampsia management with furosemide: a randomized clinical trial. Obstet Gynecol. 2005 Jan;105(1):29-33. doi: 10.1097/01.AOG.0000148270.53433.66. — View Citation

Atterbury JL, Groome LJ, Hoff C. Blood pressure changes in normotensive women readmitted in the postpartum period with severe preeclampsia/eclampsia. J Matern Fetal Med. 1996 Jul-Aug;5(4):201-5. doi: 10.1002/(SICI)1520-6661(199607/08)5:43.0.CO;2-O. — View Citation

Bigelow CA, Pereira GA, Warmsley A, Cohen J, Getrajdman C, Moshier E, Paris J, Bianco A, Factor SH, Stone J. Risk factors for new-onset late postpartum preeclampsia in women without a history of preeclampsia. Am J Obstet Gynecol. 2014 Apr;210(4):338.e1-338.e8. doi: 10.1016/j.ajog.2013.11.004. Epub 2013 Nov 7. — View Citation

Chames MC, Livingston JC, Ivester TS, Barton JR, Sibai BM. Late postpartum eclampsia: a preventable disease? Am J Obstet Gynecol. 2002 Jun;186(6):1174-7. doi: 10.1067/mob.2002.123824. — View Citation

Clark SL, Belfort MA, Dildy GA, Herbst MA, Meyers JA, Hankins GD. Maternal death in the 21st century: causes, prevention, and relationship to cesarean delivery. Am J Obstet Gynecol. 2008 Jul;199(1):36.e1-5; discussion 91-2. e7-11. doi: 10.1016/j.ajog.2008.03.007. Epub 2008 May 2. — View Citation

Filetti LC, Imudia AN, Al-Safi Z, Hobson DT, Awonuga AO, Bahado-Singh RO. New onset delayed postpartum preeclampsia: different disorders? J Matern Fetal Neonatal Med. 2012 Jul;25(7):957-60. doi: 10.3109/14767058.2011.601365. Epub 2011 Aug 16. — View Citation

Hirshberg A, Downes K, Srinivas S. Comparing standard office-based follow-up with text-based remote monitoring in the management of postpartum hypertension: a randomised clinical trial. BMJ Qual Saf. 2018 Nov;27(11):871-877. doi: 10.1136/bmjqs-2018-007837. Epub 2018 Apr 27. — View Citation

Lubarsky SL, Barton JR, Friedman SA, Nasreddine S, Ramadan MK, Sibai BM. Late postpartum eclampsia revisited. Obstet Gynecol. 1994 Apr;83(4):502-5. doi: 10.1097/00006250-199404000-00003. — View Citation

Matthys LA, Coppage KH, Lambers DS, Barton JR, Sibai BM. Delayed postpartum preeclampsia: an experience of 151 cases. Am J Obstet Gynecol. 2004 May;190(5):1464-6. doi: 10.1016/j.ajog.2004.02.037. — View Citation

Perdigao JL, Lewey J, Hirshberg A, et al. LB 4: Furosemide for Accelerated Recovery of Blood Pressure Postpartum: a randomized placebo controlled trial (FoR BP). American Journal of Obstetrics & Gynecology. 2020;222(1):S759-S760.

Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005 Feb;105(2):402-10. doi: 10.1097/01.AOG.0000152351.13671.99. — View Citation

Veena P, Perivela L, Raghavan SS. Furosemide in postpartum management of severe preeclampsia: A randomized controlled trial. Hypertens Pregnancy. 2017 Feb;36(1):84-89. doi: 10.1080/10641955.2016.1239735. Epub 2016 Nov 11. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to Discharge	Time until discharge from the hospital	Randomization through discharge, up to 7 days
Secondary	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
Secondary	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
Secondary	Breastfeeding Continuation Rate	Proportion of participants continuing to breastfeed of those who initiated breastfeeding after delivery	2 weeks postpartum, 6 weeks postpartum