Clinical trial NCT04343235: Postpartum Management of Gestational Hypertensive Disorders Using Furosemide
Official title: Postpartum Management of Gestational Hypertensive Disorders Using Furosemide: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hypertension, Pregnancy-Induced
Keywords: pregnancy induced hypertension
preeclampsia
furosemide
Lead sponsor: Wright State University
Sponsor class: OTHER
First posted: 2020-04-13
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: TREATMENT

Brief summary: * The main purpose of this study is to learn if incorporating a loop diuretic such as furosemide along with labetalol in the routine management of postpartum gestational hypertensive disorders could lower the need for additional anti-hypertensive agents to control blood pressures, improve blood pressures (as measured by systolic blood pressure, diastolic blood pressure and mean arterial blood pressures), shorten hospital stays and decrease readmissions for patients with gestational hypertensive disorders.
* Based on a study by Veena et al1, there is reason to believe that the addition of furosemide to other anti-hypertensives may help decrease the need to add or increase the dose of medication to control blood pressures. There may be potential to shorten hospital stays and decrease readmissions, as well. Collecting data will be done using a prospective, randomized 1:1 controlled study assigning postpartum patients with a gestational hypertensive diagnosis to either labetalol alone or labetalol plus furosemide.
* The study will be performed in the postpartum wing of Miami Valley Hospital Main Campus and would use patients who have consented to participate in the study with enrollees coming from the OB Staff population.

Detailed description: Background and Literature Review

* There have been four documented studies investigating loop diuretics in the management of postpartum hypertensive disorders- Matthews et al2, Ascarelli et al3, Amorim et al4, and Veena et al. Of these studies, only Amorim and Veena were able to show statistical significance on any parameters. Amorim was able to show that there was an improvement of SBP, DBP and MAP, but the research was only presented as an abstract at a conference and not published, thereby making it impossible to draw any conclusions or practice guidelines. Veena demonstrated that by using furosemide and nifedipine in combination, the need for additional antihypertensive medication in severe pre-eclampsia in the postpartum period was reduced when compared to nifedipine alone.
* A systematic review5 of postpartum hypertensive disorder management suggested that there was insufficient data to recommend any single pharmacological intervention at this time in the management of gestational hypertensive disorders. The review emphasized the need for further studies to be conducted to help guide management of patients affected by gestational hypertensive disorders in the future.

Objectives

● Main Question

* Does the use of furosemide plus labetalol improve blood pressures in the postpartum period of patients with gestational hypertensive disorders versus labetalol alone?
* Primary

  ■ Will there be a requirement to escalate antihypertensive therapy to control blood pressures
* Secondary

  * Improvement of gestational hypertensive disorders by measurement of systolic blood pressure, diastolic blood pressure and mean arterial pressure
  * Shortened hospital stay in patients with hypertensive disorders
  * Breastfeeding status at 1 week postpartum visit in mothers planning to breastfeed
  * Readmission for postpartum hypertensive disorders

Significance to patient, institution, and profession

* As a referral center and being the region's leader, Miami Valley is very accustomed to accepting transfers of high acuity patients often times with hypertensive disorders being the root cause of the transport
* The majority of the OB staff population being served at Miami Valley Hospital is African American. According to Myatt6, the incidence of pre-eclampsia in the African American population is greater than double the Caucasian population (11% to 5%) thereby making this study very applicable to the patient population served at Miami Valley Hospital.
* With the construct of the study, costs abe kept low by utilizing already established resources and practices (blood pressure cuffs, nurses, routine one week blood pressure checks) while only adding on the unit cost of furosemide.
* If treatment with labetalol and furosemide is found to be useful, it would be not only a very inexpensive, cost effective way of improving patient outcomes and possibly decreasing lengths of stay stateside, but in improving global practice in places that are lacking in resources privy to first world countries.

Methods

* The study would be designed as:

  * A prospective randomized 1:1 controlled trial including postpartum women with gestational hypertension or preeclampsia
  * Patients with chronic hypertension would be excluded from the study
  * One arm receiving 200mg labetalol BID alone on PPD#1 or 24 hours after magnesium sulfate
  * One arm receiving 200mg labetalol BID and a five day course of furosemide 20mg QD on PPD#1 or 24 hours after magnesium sulfate
  * Recording any occurrence when an increased amount of labetalol is needed to maintain blood pressures below 150 SBP and/or 100 DBP per ACOG recommendations.7

    ■ In the event of persistently elevated blood pressures, labetalol will be increased to 400mg TID and escalated to 600mg TID and finally 800mg TID as indicated
  * Measurement of blood pressure every four hours after administration until patient discharge
  * Measurement of urine output every 12 hours until discharge
  * Compare average systolic, diastolic and mean arterial pressures between the two groups during admission and at one week postpartum
* Data will be collected using the OB Staff population at Miami Valley Hospital Main Campus.
* The research will be analyzed and interpreted by the research team conducting the study.
* Potential difficulties and limitations include compliance concerns of mandatory one week blood pressure follow up appointment.
* Using the Veena et al paper as a frame of reference, a sample size of 140 divided evenly across the two treatment arms would achieve statistical significance in determining the need to escalate anti-hypertensive therapy.
* The unit cost of one tablet of labetalol 200mg and furosemide 20mg is currently $0.32 and $1.23, respectively. 8,9
* The study would use already readily available automated blood pressure cuff machines on the postpartum wing.

Eligibility criteria: Inclusion Criteria:

* Postpartum women delivering at Miami Valley Hospital
* Diagnosis of gestational hypertension or preeclampsia
* Able to provide written informed consent

Exclusion Criteria:

* Diagnosis of chronic hypertension
* Allergy to study medications
* Unable to understand English

Primary outcomes:
measure: Change of Dose for Antihypertensive Therapy
timeFrame: Change in dose of hypertensive therapy from randomization until hospital discharge (up to 7 days)
Secondary outcomes:
measure: Change of Gestational Hypertensive Disorder Symptoms (Systolic BP)
timeFrame: Average systolic blood pressure for Day 0, Day 1, and Day 2
measure: Change of Gestational Hypertensive Disorder Symptoms (Mean Arterial Pressure)
timeFrame: Average mean arterial pressure on Day 0, Day 1, and Day 2
measure: Change of Gestational Hypertensive Disorder Symptoms (Diastolic BP)
timeFrame: Average diastolic blood pressure on Day 0, Day 1, and Day 2
measure: Hospital Length of Stay
timeFrame: Number of days of hospital stay from randomization to discharge
measure: Breastfeeding Status
timeFrame: at 1 week postpartum visit
measure: Hospital Readmission
timeFrame: up to 14 days after discharge
Other outcomes:
Locations:
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
Study officials:
affiliation: Wright State University
name: Sheela Barhan, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Matthews G, Gornall R, Saunders NJ. A randomised placebo controlled trial of loop diuretics in moderate/severe pre-eclampsia, following delivery. J Obstet Gynaecol. 1997 Jan;17(1):30-2. doi: 10.1080/01443619750114040.
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.
citation: Cairns AE, Pealing L, Duffy JMN, Roberts N, Tucker KL, Leeson P, MacKillop LH, McManus RJ. Postpartum management of hypertensive disorders of pregnancy: a systematic review. BMJ Open. 2017 Nov 28;7(11):e018696. doi: 10.1136/bmjopen-2017-018696.
citation: Myatt L, Clifton RG, Roberts JM, Spong CY, Hauth JC, Varner MW, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Iams JD, Sciscione A, Harper M, Tolosa JE, Saade G, Sorokin Y, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. First-trimester prediction of preeclampsia in nulliparous women at low risk. Obstet Gynecol. 2012 Jun;119(6):1234-42. doi: 10.1097/AOG.0b013e3182571669.
citation: Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.