Postpartum Management of Gestational Hypertensive Disorders Using Furosemide: A Randomized Controlled Trial
Phase: PHASE4
Conditions: Hypertension, Pregnancy-Induced
Sponsor: Wright State University

 
Protocol version date 01/09/2020                                                                                          1 
 
Research Proposal 
Zachary Candela, DO 
WSU-SOM, OBGYN, PGY-2  
 
 
Title 
 
● Postpartum management of gestational hypertensive disorders using furosemide: A 
randomized controlled trial  
 
Investigators 
 
● Primary Investigator 
○ Zachary Candela, DO, PGY-2, Capt, USAF 
■ (724) 815-8576 
■ zachary.candela@wright.edu 
 
● Investigators 
○ Samantha Wiegand, MD, MFM subspecialist at MFMUG 
■ (937) 545-4869 
■ slwiegand@premierhealth.com 
 
○ Sheela Barhan, MD, WSU-SOM Teaching Faculty 
■ (937) 219-5741 
■ sheela.barhan@wright.edu 
 
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.  
● Based on an estimated 8% need for increase in anti-hypertensive medication in the 
furosemide group and a 26% need in the standard treatment arm, to achieve 90% power 

 
Protocol version date 01/09/2020                                                                                          2 
 
with a 2-sided alpha of 0.05, we calculate 96 patients per group. Analysis will be via Chi-
square or Fisher’s exact test for categorical variables. Student T-Test and Mann Whitney 
U tests will be utilized to compare continuous variables. Randomization will be 
performed using REDCap. 
● The study will be performed in the postpartum wing of Miami Valley Hospital Main 
Campus and would recruit patients who have consented to participate in the study with 
enrollees coming from the OB Staff population.  
 
Background and Literature Review 
 
● We found four 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 their 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 
■ Does the addition of a 5-day course of furosemide to labetalol avoid the 
escalation of anti-hypertensive therapy to control blood pressures. 
○ Secondary:  
■ Does the addition of furosemide to labetalol in postpartum hypertension: 
● Improve of systolic blood pressure, diastolic blood pressure and 
mean arterial pressure. 
■ Shortened hospital stay   
■ Affect breastfeeding status at 1 week postpartum visit in mothers planning 
to breastfeed. 
■ Decrease readmission for postpartum hypertensive disorders. 

 
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Significance to patient, institution, and profession 
 
● As a busy referral center with a level 3 NICU, Miami Valley care for a large number of 
patients with gestational hypertensive disorders 
● 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 our patient population. 
● With the construct of the study, we would be keeping costs 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 and basic metabolic 
panels.  
● 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, but possibly improvement in global practice in places that are 
lacking in resources privy to first world countries. 
 
Methods 
 
● A prospective randomized 1:1 controlled trial including postpartum women with 
gestational hypertension or preeclampsia 
○ Inclusion criteria: Age 18-45, Postpartum: 24-72 hours after delivery, no 
contraindications to the study medications 
○ Exclusion criteria: chronic hypertension diagnosis, creatinine levels above 1.5 
µm/L, unable to give consent 
● One arm receiving 200mg labetalol BID alone on Day#1 or at least 24 hours after 
magnesium sulfate, if given 
● One arm receiving 200mg labetalol BID and a five day course of furosemide 20mg QD 
on Day#1 or 24 hours after magnesium sulfate 
○ The 20 mg dose is the standard dose for furosemide in this population.  
● Tritrate labetalol 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 BID and escalated to 600mg BID and finally 800mg BID as indicated 
● Measurement of blood pressure every four hours until patient discharge 
● Daily BMPs to assess for electrolyte abnormalities 
● Measurement of urine output every 12 hours until discharge 
● Demographics 
○ Age (18-24, 25-34, 35-44, 45-51) 
○ Nulliparous (yes, no) 
○ BMI (underweight, normal, overweight, obese) 

 
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○ Race (Caucasian, African American, Asian, Hispanic, Other) 
○ Diabetes (yes, no) 
○ Multiple gestation (yes, no) 
○ Preterm delivery (yes, no) 
■ Gestational age at delivery 
○ Cesarean delivery (yes, no) 
○ IVF pregnancy (yes, no) 
○ History of previous gestational hypertension/pre-eclampsia (yes, no) 
○ Systemic lupus erythematosus (yes, no) 
○ Renal disease (yes, no) 
● Outcome variables 
○ Need for additional antihypertensive medication  (yes, no) 
■ Labetalol 400mg BID 
■ Labetalol 600mg BID 
■ Labetalol 800mg BID 
○ Highest systolic blood pressure (mmHg) 
○ Highest diastolic blood pressure (mmHg) 
○ Mean arterial blood pressure 
○ Daily urine output (mL) 
○ Length of postpartum stay (days) 
○ Readmission for hypertension (yes, no) 
○ Breastfeeding at 1 week postpartum (yes, no) 
● The study duration is the length of the hospital stay plus 1 week postpartum blood 
pressure check. 
● 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.  
● The unit cost of one tablet of labetalol 200mg and furosemide 40mg 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.  
 
Safety Monitoring 
Monitoring of blood pressures will be performed every four hours while on the maternity 
postpartum floor. If the patient is found to be above 160 systolic or 110 diastolic, it will be 
rechecked in fifteen minutes. If still elevated, then escalation of blood pressure medicine will be 
done. The healthcare provider will ask the patient if they are exhibiting any signs of profound 
hypertension and/or hypokalemia including headache, vision changes, dizziness, 
lightheadedness, weakness, fatigue, muscle cramping, or heart palpitations. If any of these are 
identified, a physician will be notified and will assess the patient. 
Patients will be instructed to let their doctor/nurses know if they are experiencing known 
side effects of Lasix that include new onset weakness, fatigue, muscle cramping, dizziness or 

 
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heart palpitations. If a patient has severe symptoms after discharge, they will be instructed to call 
the afterhours phone number on the consent form. 
If a patient has signs of hypokalemia, we will test lab values for potassium (K+) levels 
(Complete metabolic panel). We will continue administering Lasix if the potassium result is 
between 3.0 and 3.4 µm/L and we will administer 20 mEq KDur BID. If it is less than 3.0 µm/L 
we will stop using Lasix.  
 
 
References 
 
1) Veena, P., et al. “Furosemide in Postpartum Management of Severe Preeclampsia: 
A Randomized Controlled Trial.” Hypertension in Pregnancy, vol. 36, no. 1, 2016, 
pp. 84–89., doi:10.1080/10641955.2016.1239735. 
2) 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;17:30-2 
3) Ascarelli MH, Johnson V, McCreary H, et al. Postpartum preeclampsia 
management with furosemide: a randomized clinical trial. Obstet Gynecol 
2005;105:29-33 
4) Amormim M, Katx L, Cursino T, et al. Postpartum furosemide for accelerating 
recovery in women with severe preeclampsia: A randomized clinical trial. Int J 
Gynaecol Obstet 2015;131:E195 
5) Cairns AE, Pealing L, Duffy JMN, et al. Postpartum management of hypertensive 
disorders of pregnancy: a systematic reivew. BMJ Open 2017;7:e018696. 
doi:10.1136/bmjopen-2017-018696 
6) Myatt  L, Clifton  RG, Roberts  JM,  et al: First-trimester prediction of 
preeclampsia in nulliparous women at low risk. Obstet Gynecol 119(6):2012a 
7) ACOG Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: 
American college of obstetricians and gynecologists,  2013. 
8) “Labetalol Prices, Coupons & Patient Assistance Programs.” Drugs.com, 
www.drugs.com/price-guide/labetalol. 
9) “Lasix Prices, Coupons & Patient Assistance Programs.” Drugs.com, 
www.drugs.com/price-guide/lasix.