LAPP: Lasix for the Prevention of De Novo Postpartum Hypertension
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lasix (furosemide) Furosemide 20 mg, oral, once daily for 5 days |
Drug: Furosemide
Furosemide 20 mg pill taken daily for 5 days
Other Names:
|
| Placebo Comparator: Placebo Identical-appearing placebo, oral, once daily for 5 days |
Other: Placebo
Identical-appearing placebo pill taken daily for 5 days
|
Outcome Measures
Primary Outcome Measures
- 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
- Rate of de novo postpartum preeclampsia [Discharge (up to 7 days), 2 weeks postpartum, 6 weeks postpartum]
Proportion of participants who develop de novo postpartum hypertension
- Frequency of hypertensive episodes [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 [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 [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 [Randomization through discharge, up to 7 days]
Time until discharge from the hospital
- Rate of severe maternal morbidity [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 [2 weeks postpartum, 6 weeks postpartum]
Mean frequency of triage or ED presentation/readmission for hypertensive-related complaints
- Breastfeeding continuation rate [2 weeks postpartum, 6 weeks postpartum]
Proportion of participants continuing to breastfeed of those who initiated breastfeeding after delivery
Eligibility Criteria
Criteria
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
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At least 18 years of age
-
English or Spanish speakers
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Columbia University Irving Medical Center | New York | New York | United States | 10032 |
Sponsors and Collaborators
- Columbia University
Investigators
- Principal Investigator: Cynthia Gyamfi-Bannerman, MD, MSc, University of California San Diego Health
- Principal Investigator: Russell S Miller, MD, Columbia University
Study Documents (Full-Text)
None provided.More Information
Publications
- ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019 Jan;133(1):1. doi: 10.1097/AOG.0000000000003018.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Lubarsky SL, Barton JR, Friedman SA, Nasreddine S, Ramadan MK, Sibai BM. Late postpartum eclampsia revisited. Obstet Gynecol. 1994 Apr;83(4):502-5. Review.
- 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.
- 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. Review.
- 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.
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