Clinical trial NCT04343235
Conditions: Hypertension, Pregnancy-Induced
Keywords: pregnancy induced hypertension preeclampsia furosemide
Sponsor: Wright State University
Start date: 2020-05-01; Completion date: 2022-06-30
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: labetalol + furosemide arm 2: labetalol only
Interventions: intervention 1: furosemide intervention 2: labetalol
Intervention descriptions: intervention 1: five day course of furosemide 20mg QD intervention 2: 200mg labetalol BID

Protocol documents:
ICF_002.pdf: 
Version: 3
Date: 01/29/2021
Page 1 of 11
INFORMED CONSENT AND AUTHORIZATION
Postpartum management of gestational hypertensive disorders using 
furosemide: A randomized controlled trial 
Investigator(s) name, Degree, University Department, & address:

Zachary G Candela, DO, Wright State University Boonshoft School of Medicine, 
OBGYN

Sheela Barhan, MD,  Wright State University Boonshoft School of Medicine, 
OBGYN

Samantha Wiegand, MD,  Perinatal Partners, Miami Valley Hospital

Rose Maxwell, PhD, Wright State University Boonshoft School of Medicine, 
OBGYN
Site(s) where study is to be conducted:

Miami Valley Hospital, Dayton, OH

Five Rivers Center for Women’s Health, Dayton, OH
Phone number for subjects to call for questions

(937) 208-2965 - Wright State Physicians/ WSU-BSOM OBGYN Department

(937) 208-8000 after hours
Introduction
The purpose of this consent form is to give you information about this research study.  It 
will describe the purpose, procedures, benefits, risks, and discomforts of this study.  
The principal investigator and/or the study staff will discuss this study with you and 
explain everything in detail.  Please ask them to explain any words or information that 
you do not clearly understand.
It is up to you to decide whether or not to take part in this study.  If you choose not to 
participate your decision will not affect your current or future relationship with Wright 
State University or Premier Health nor will it affect your health care at Premier Health.  If 
you decide to participate, you are free to withdraw at any time without affecting that 
relationship.  Please read this entire consent form and take your time to make your 
decision.  We encourage you to talk to your doctor, your family, and/or your friends 
before you decide.
Who is conducting and funding this research study?
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Wright State University (WSU) will be conducting this trial under the direction of Dr. 
Zachary Candela, principal investigator.  This study is being carried out with funds 
received from the WSU Department of OBGYN.
Why is this research study being done?
The purpose of this study is to compare standard treatment of postpartum gestational 
hypertensive disorders using labetalol vs experimental treatment using labetalol plus 
furosemide, which is an FDA approved diuretic, to see if there is a difference in blood 
pressure control. 
Why am I being asked to participate in this research study?
You are being asked to take part in this study because you have elevated blood 
pressures that are caused by a gestational hypertensive disorder such as pre-eclampsia 
or gestational hypertension. You may benefit from this experimental treatment regimen. 
How many people will be in this study?
Approximately 192 women will participate in this study (96 in the labetalol arm and 96 in 
the labetalol plus furosemide arm).
What will happen if I take part in this research study? 
If you agree to be in this study, the following will happen:
BEFORE YOU BEGIN THE STUDY – SCREENING PROCEDURES 
You will have the following things done:

History and physical examination which will include checking your heart rate, 
blood pressure and temperature. 

Weight measurements

Review of medications and supplements you are currently taking.
These are part of your regular care.
DURING THE STUDY
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This research will take place at Miami Valley Hospital. 
If the screening exams, tests or procedures show that you can continue to be in the 
study, and you choose to take part, then the following will be done.  
If you agree to take part in this study, you will be "randomized" into one of the study 
groups described below. Randomization means that you are put into a group by chance 
(like pulling numbers out of a hat). A computer program will place you in one of the 
study groups. Neither you nor your doctor can choose the group (also referred to as an 
“arm”) you will be in. You will have an equal chance of being placed in any group.
If you are in Arm A you will be given the current standard treatment for gestational 
hypertensive disorders which consists of labetalol. You will take labetalol as long as 
your doctor recommends that you need it to control your blood pressure.
If you are in Arm B you will be given the experimental treatment for gestational 
hypertensive disorders which consists of labetalol plus furosemide.  You will take 
labetalol as long as your doctor recommends that you need it to control your blood 
pressure. You will take furosemide for 5 days.
The following procedures will be completed:

You will receive labetalol twice daily and if you are in the furosemide arm, you will 
receive one dose of furosemide daily.

Your urine output will be measured every twelve hours. This will require you to 
urinate into a collection unit while sitting on the toilet. 

You will be asked questions about your medical history, and information about 
any drugs that you are taking from your last visit. 

A physical exam including vital signs (blood pressure and heart rate), will be 
performed. 

You will have blood drawn for routine lab work.  (About 6mL or 2 teaspoons of 
blood will be drawn). 
How long will I be in this research study?
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If you choose to take part, you will be in the study for the duration of your hospital stay 
and up to 1 week when you have your blood pressure check appointment. Typically, 
postpartum patients remain in the hospital somewhere between 2-4 days. We will also 
ask that you come in for a routine one week blood pressure check to see how you are 
doing after discharge from the hospital. 
Can I stop being in this research study? 
If you decide to participate, you are free to withdraw your consent and discontinue 
participation at any time without any penalty.  Your decision will not affect your ability to 
receive medical care for your disease and you will not lose any benefits to which you 
would otherwise be entitled. If you withdraw from the study, or the study medication is 
stopped for any reason: 

You will need to alert your treatment team (nurse, resident, attending, 
study coordinator) that you are electing to leave the study

You will no longer receive the study medications, but your treatment team 
will still take care of you and give you the current standard of care for 
gestational hypertensive disorders including blood pressure checks, 
medications and routine follow up.
The principal investigator or study staff may also withdraw you from the study and the 
study medication may be stopped [if applicable], without your consent for one or more of 
the following reasons: 

Failure to follow the instructions of the research study staff.

Pregnancy. 

You need treatment not allowed in the study.

The study is cancelled. 

The principal investigator believes it is in your best interest.
What are the potential risks and discomforts from being in this research study?
Although highly unlikely, there is a small risk of loss of privacy regarding this study 
(revealing to others that you are taking part in this study) or confidentiality (revealing 
information about you to others to whom you have not given permission to see this 
information).
Risks and side effects of furosemide (Lasix):
More common reactions:
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Fatigue (tiredness)
Urinary frequency
Dizziness
Nausea/vomiting
Muscle cramps
Hypokalemia (low levels of potassium in the blood)
Hypotension, orthostatic (low blood pressure when standing up)
Diarrhea
ALT, AST elevated
Blurred vision
Anorexia (eating less from loss of appetite)
Abdominal cramps
Pruritis (itching)
Rash
Hyperuricemia (high levels of uric acid in the blood)
Hyperglycemia (high blood sugar)
Hypocalcemia (low levels of calcium in the blood)
Hypomagnesemia (low levels of magnesium in the blood)
Tinnitus (ringing in the ears)
Paresthesia (feeling of tingling, tickling, prickling or burning)
Photosensitivity (increased sensitivity of the skin to light)
Less common reactions: 
Hypokalemia, severe (low levels of potassium in the blood)
Electrolyte imbalance, severe (abnormal levels of electrolytes such as sodium, 
potassium, calcium)
Metabolic alkalosis (increased pH in tissues)
Hypovolemia (decreased blood volume) /dehydration 
Ototoxicity (toxic condition affecting the inner ear or the auditory nerve)
Thrombocytopenia (abnormally low levels of platelets in the blood)
Anemia, hemolytic (anemia due to having fewer red blood cells)
Aplastic anemia (anemia due to bone marrow producing very few new red blood cells)
Leukopenia (abnormally low number of white blood cells in the blood)
Agranulocytosis (abnormally low number of granulocytes/neutrophils tha may lead to 
increased risk of infection)
Thrombosis (blood clots)
Anaphylaxis (allergic reaction)
Vasculitis (inflammation of blood vessels)
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Pancreatitis (inflammation of the pancreas) 
Stevens-Johnson Syndrome (severe inflammation of the skin and mucous 
membranes)
SLE exacerbation (worsening of symptoms lupus)
Toxic epidermal necrolysis (severe skin reaction involving the top layer of skin 
separating from lower layers of the skin)
Please let your doctor know if you are experiencing new onset weakness, fatigue, muscle 
cramping, dizziness or heart palpitations as these can be signs of hypokalemia, a side 
effect from taking furosemide.
Unknown:
There may be risks from furosemide that are not known at this time.  
Are there benefits to taking part in this research study? 
You may not receive any personal benefit from being in the study. It is possible that you 
may benefit by having better control of your blood pressures in the postpartum period. It 
may also lead you to have a shorter hospital stay and lower your rate of being 
readmitted for blood pressure control later. However, there is no guarantee that you will 
benefit from being in this study.
The researchers hope that information learned from your participation in this study will 
increase knowledge about which way is best to treat patients like you. This knowledge 
will help make it possible to provide the best type of treatment for patients in the future. 
While you may or may not personally benefit from being in this study, your participation 
will provide a benefit to others with this condition and to society. 
What other options are there?
If you decide not to participate in this study, you will receive the standard of care 
treatment for your condition.
What about privacy and confidentiality?
The people who will know that you are a research subject are members of the research 
study staff, and if appropriate, your physicians and nurses.  No information about you, 
or provided by you, during the research, will be disclosed to others without your written 
permission, except if necessary, to protect your rights or welfare or if required by law. 
The following groups will have access to study records that identify you:
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
Food and Drug Administration (FDA) 

Wright State University Institutional Review Board (IRB, including the WSU 
IRB Office and the Office of Research and Sponsored Programs

Office of Human Research Protections, under the Department of Health and 
Human Services
A possible risk of the research is that your participation in the research or information 
about you and your health might become known to individuals outside of the research 
team.
Identifiers might be removed from your identifiable private information (or/and 
identifiable biospecimens). After such removal, the information could be used for future 
research studies or distributed to another investigator for future research studies without 
your (or your legally authorized representative’s) consent. 
When the results of the research are published or discussed in conferences, no 
information will be included that would reveal your identity.  
FDA Clinical Trial Registry
A description of this clinical trial will be available on http://www.clinicaltrials.gov, as 
required by U.S. law.  This website will not include information that can identify you.  At 
most, the website will include a summary of the results.  You can search this website at 
any time.
What if I am injured as a result of my participation in the research study? 
If you feel that you have been injured as a result of participating in the research, contact 
the researcher Dr. Zachary Candela at (937) 208-2287 to talk to them about your illness 
or injury. In the event of an emergency, dial 911 or go to your nearest emergency 
department. 
There are no plans for Wright State University to provide free medical care or to pay for 
research-related illnesses or injuries, or to provide other forms of compensation (such 
as lost wages or pain and suffering) to you for research related illnesses or injuries.
You or your insurance company will be billed for this medical care.  Your insurance 
company may not pay for some or all of this medical care because you are participating 
in a research study.  
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By signing this form you will not give up any legal rights.
What are the costs for participating in this research study?  
You or your insurer will be responsible for paying for the cost of the following:

Daily basic metabolic panel blood test
The cost for the furosemide will be paid by the study.
Will I be reimbursed for any of my expenses or paid for my participation in this 
research?
You will not be reimbursed for participating in this research study.   
Will I be told about new information that may affect my decision to participate in 
this research study? 
During the course of the study, you will be informed of any significant new research 
information (either good or bad), such as changes in the risks or benefits resulting from 
participation in the research or new alternatives to participation, that might cause you to 
change your mind about continuing in the research.  If new information is provided to 
you, you may be asked to sign a consent form that includes the new information.
Who should I contact if I have questions? 
Contact the researcher, Dr. Zachary Candela, at (937) 208-2287 if you have any 
questions about this study or your part in it or if you have questions, concerns or 
complaints about the research.
If you have any questions about your rights as a research subject, you may call the 
Wright State University Institutional Review Board (IRB) at (937) 775-4462. The IRB is 
an independent committee composed of members of the University community, staff of 
the institutions, as well as lay members of the community not connected with these 
institutions.  The IRB has reviewed this study.
What are my rights/responsibilities as a research subject?
As a subject, your responsibilities include:
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
Follow the instructions of the research study staff.

Take the study drug as instructed. 

Keep your routine one week postpartum blood pressure check appointment.  If it 
is necessary to miss an appointment, please contact the Five Rivers Women’s 
Health Center staff to reschedule as soon as you know you will miss the 
appointment. You can reach them at (937) 208-2007.

Tell the research study staff about any side effects, doctor visits, or 
hospitalizations that you may have. 

Contact your doctor you have any of these side effects: new onset of weakness, 
fatigue, muscle cramping, dizziness or heart palpitations.

Ask questions as you think of them.

Tell the research staff if you change your mind about staying in the study.
While participating in this research study, you should not take part in any other research 
project without approval from the research staff of each study.  
Authorization to Use and Disclose Your Health Information 
State and Federal laws, including the Health Insurance Portability and Accountability 
Act (HIPAA), require researchers to protect the privacy of your health information. This 
section of the consent form describes how researchers, with your authorization 
(permission), may use and release (disclose or share) your protected health information 
(PHI) for this research study. Please read this section of the consent form carefully. 
If you sign this document, you give permission to Dr. Zachary Candela and his research 
team to use or disclose (release) the following protected health information:

Your medical records for past medical conditions and medications related to 
your cardiovascular health

All information (research records and medical records) created during your 
participation in this research study

All information related to illness, readmissions and/or hospitalizations that 
occur during your participation in this study
The research team needs this information to conduct the study.  This is a study that 
looks at controlling blood pressures in the postpartum state by adding a diuretic 
(furosemide) to current standard of care.
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To maintain the integrity of this research, you might not have access to any health 
information developed as part of this study until it is completed.  At that point, you 
generally would have access to your health information.
Disclosure of your protected health information 
 
If you sign this form, the researchers may share your health information during the 
conduct of the study with: 

Non-WSU/PH researchers or organizations working with WSU/PH 
researchers.

Law enforcement or other agencies, when required by law

WSU’s Institutional Review Board (or other IRB of record), which oversees 
our research 

Representatives of government agencies in the United States and other 
countries (i.e. Food and Drug Administration and the Office of Human 
Research Protection)

Other authorized WSU/PH Officials who oversee research and clinical 
care
  
The people listed above will use and share your health information to review the quality, 
safety, and results of the research and may also do additional research.
Please understand that these persons/organizations who may receive your health 
information may not be required by U.S. Federal privacy laws (such as HIPAA) to 
protect it and may share your information with others without your permission. 
This authorization does not have an expiration date.
 
However, you can change your mind and cancel this authorization at any time. To 
cancel this authorization, you must write the study investigator listed at the beginning of 
this consent form.
 
If you cancel this authorization, you will no longer be allowed to take part in the research 
study.  If you cancel this authorization, health information you had already allowed us to 
obtain may still be used and disclosed by researchers in order to maintain the integrity 
and reliability of the research, and to report any adverse (bad) effects that may have 
happened to you.
 
Right to refuse to sign this Authorization 
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You have the right to refuse to sign and give your authorization. If you do not sign this 
form, your non-research related treatment, payment or enrollment in any health plans, 
or your eligibility for other medical benefits at Premier Health will not be affected in any 
way.  
However, if you do not sign this form, you will not be able to participate in this research 
study.  
Signature of Subject
I have read (or someone has read to me) the above information.  I have been given an 
opportunity to ask questions and my questions have been answered to my satisfaction.  
I agree to participate in this research and authorize the use and disclosure of my 
protected health information for this study.  I will be given a copy of this signed and 
dated form.
Signature
Date
Printed Name
________________________
Signature of Person Obtaining Consent and Authorization
_________________________
Date 
______________________
Printed Name of Person Obtaining Consent and Authorization
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SAP_003.pdf: 
 
 
 
Version date 1/9/2020 
 
 
 
Postpartum management of gestational hypertensive disorders using furosemide: A randomized 
controlled trial   
Statistical Analysis Plan 
Version Jan 9, 2020 
 
Rose A. Maxwell, PhD; Zachary Candela, DO; Sheela Barhan, MD 
 
The statistical analysis plan is based on the objectives of the study as follows: 
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.  
Analysis plan: Randomization groups (labetalol + furosemide vs labetalol alone) will be 
compared using a Fisher’s Exact test for number of patients who have had an escalation of 
labetalol dose at any time during their hospital stay. 
Secondary:   
Does the addition of furosemide to labetalol in postpartum hypertension:  
1. Improve of systolic blood pressure, diastolic blood pressure and mean arterial pressure.  
Analysis plan: Randomization groups will be compared on daily means for each outcome by 
repeated measures ANOVA to determine difference in outcomes across time (Day 0/Baseline, 
Day 1, and Day 2). One repeated measures ANOVA will be performed for each of the three 
outcomes (systolic blood pressure, diastolic blood pressure, and mean arterial pressure). 
2. Shortened hospital stay    
Analysis plan: Randomization groups will be compared on hospital length of stay using a Student 
T-test.  
3. Affect breastfeeding status at 1 week postpartum visit in mothers planning to breastfeed.  
Analysis plan: Randomization groups will be compared on breastfeeding status at the 
postpartum visit using a Fisher’s Exact test. 
4. Decrease readmission for postpartum hypertensive disorders. 


 
 
 
Version date 1/9/2020 
 
 
 
Analysis plan: Randomization groups will be compared on the number of participants who were 
hospitalized after discharge using a Fisher’s Exact test. 

Prot_000.pdf: 
 
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. 


 
Protocol version date 01/09/2020                                                                                          3 
 
 
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) 


 
Protocol version date 01/09/2020                                                                                          4 
 
○ 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 


 
Protocol version date 01/09/2020                                                                                          5 
 
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.