A Randomized Control Trial of Furosemide or Placebo With Usual Antihypertensives in the Antepartum Management of Severe Hypertension With Wide Pulse Pressure
Phase: PHASE3
Conditions: Pre-Eclampsia, Hypertension in Pregnancy, Pregnancy Complications, Hypertension, Pregnancy-Induced
Sponsor: Melanie Maykin, MD

A randomized control trial of furosemide or placebo with usual antihypertensives in the antepartum management of 
severe hypertension with wide pulse pressure 
Version 2 
Protocol Number I 
 
 
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A randomized control trial of furosemide or placebo with usual antihypertensives in the 
antepartum management of severe hypertension with wide pulse pressure 
Protocol Number I Version 2 
02/21/20 
 
Principal Investigator: Pai-Jong Stacy Tsai, MD, MPH, MCR 
Sub-Investigator: Melanie Maykin, MD 
 
Research Site: Kapi’olani Medical Center for Women and Children 
1319 Punahou Street 
Honolulu, Hawaii  
(808) 983-6000 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A randomized control trial of furosemide or placebo with usual antihypertensives in the antepartum management of 
severe hypertension with wide pulse pressure 
Version 2 
Protocol Number I 
 
 
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Protocol Title:  A randomized control trial of furosemide or placebo with usual 
antihypertensives in the antepartum management of severe hypertension with wide pulse 
pressure 
Version Date: 2/21/20 
Protocol Number: I 
 
Principal Investigator:  Pai Jong Stacy Tsai, MD 
Sub-Investigator(s): Melanie Maykin, MD 
Research Site(s): Kapiolani Medical Center for Women and Children 
 
Section I:  Purpose and Background 
1. Purpose   
 
Primary objective: To determine whether the addition of intravenous furosemide with usual 
antihypertensives is associated with a reduction in mean systolic blood pressure from 
baseline compared to treatment with placebo plus usual antihypertensives (intravenous 
labetalol, intravenous hydralazine, or oral immediate release nifedipine) for the management 
of severe antepartum hypertension.  
 
Secondary objectives: 
To determine whether the addition of intravenous furosemide with usual antihypertensives is 
associated with a reduction in mean diastolic blood pressure compared to treatment with 
placebo plus usual antihypertensives listed above. 
 
 
2. Background  
Introduce and provide support for the research being proposed.  Basic 
information relevant to the context of the research question and study design 
should be included in this section.  Additionally, this section should be written in 
a way that a person who is not an expert in the field can understand.   
 
Blood pressure is a measure of blood flow and resistance in blood vessels. In normal 
pregnancy, total blood volume increases while systemic vascular resistance decreases, 
thereby leading to an overall reduction in blood pressure with return to baseline at term. 
Hypertensive disorders in pregnancy, including preeclampsia, are a polymorphic 
syndrome characterized by elevated blood pressures which can affect multiple organ 
systems1. Although the exact mechanism of preeclampsia has yet to be determined, 
previous studies have shown that there may be two distinct phenotypes – one 
characterized by vasoconstriction and diminished micro-circulation and the other 
involving a hyperdynamic high cardiac output state2,3.  
 
Given its potential for both significant maternal and fetal morbidity, hypertensive 
disorders in pregnancy comprise a substantial proportion of antepartum admissions. 
Management of acute severe hypertension (systolic BP³ 160 or diastolic BP³ 110) is 
important to reduce the risk of stroke, hypertensive encephalopathy, placental abruption, 
and heart failure or myocardial infarction4. In the antepartum and intrapartum period, the 
use of antihypertensives including labetalol, nifedipine, and hydralazine have been well-
described4. Despite these options for blood pressure control, preeclampsia can be a 
progressive disorder that may not respond to the aforementioned agents. 

A randomized control trial of furosemide or placebo with usual antihypertensives in the antepartum management of 
severe hypertension with wide pulse pressure 
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In preeclampsia manifested by high blood volume due to salt and water retention rather 
than vasoconstriction, standard antihypertensives may be less effective. Furosemide is a 
commonly used diuretic that can lower blood pressure by inhibiting the absorption of 
sodium, chloride, and water, thereby decreasing the volume of blood that the heart 
pumps. The onset of action of action of IV furosemide is 5 minutes, with peak effect at 
30 minutes, and duration of action of 2 hours5. 
 
Previous studies have demonstrated the safety and efficacy of furosemide to treat 
preeclampsia in the antepartum and postpartum period as well as its utility in treating 
heart failure in pregnant women6,7. To our knowledge, no randomized studies exist that 
investigate the use of furosemide in treating hypertension in the antepartum period. We 
aim to determine the utility of the addition of furosemide to usual antihypertensives in 
this clinical setting. 
 
 
 
 
References 
 
1. Grindheim G, Estensen ME, Langesaeter E, Rosseland LA, Toska K. Changes in blood 
pressure during healthy pregnancy: a longitudinal cohort study. J Hypertens. 2012 
Feb;30(2):342-50. doi: 10.1097/HJH.0b013e32834f0b1c. PubMed PMID: 22179091. 
2. Phillips JK, Janowiak M, Badger GJ, Bernstein IM. Evidence for distinct preterm and 
term phenotypes of preeclampsia. J Matern Fetal Neonatal Med. 2010 Jul;23(7):622-
6. doi: 10.3109/14767050903258746. PubMed PMID: 20482241; PubMed Central 
PMCID: PMC2885458. 
3. Easterling TR, Benedetti TJ, Schmucker BC, Millard SP. Maternal hemodynamics in 
normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol. 1990 
Dec;76(6):1061-9. PubMed PMID: 2234714. 
4. ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet 
Gynecol. 2019 Jan;133(1):e1-e25. doi: 10.1097/AOG.0000000000003018. PubMed 
PMID: 30575675. 
5. https://www.uptodate.com/contents/furosemide-drug 
information?search=furosemide&source=panel_search_result&selectedTitle=1~148&usa
ge_type=panel&kp_tab=drug_general&display_rank=1 
 
6. Tamás P, Hantosi E, Farkas B, Ifi Z, Betlehem J, Bódis J. Preliminary study of the 
effects of furosemide on blood pressure during late-onset pre-eclampsia in patients with 
high cardiac output. Int J Gynaecol Obstet. 2017 Jan;136(1):87-90. doi: 
10.1002/ijgo.12019. Epub 2016 Nov 3. PubMed PMID: 28099709. 
7. 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. PubMed 
PMID: 15625138. 
8. Duley L, Meher S, Jones L. Drugs for treatment of very high blood pressure during 
pregnancy. Cochrane Data- base of Systematic Reviews 2013, Issue 7. Art. No.: 
CD001449. (Systematic Review and Meta-Analysis). PMID: 23900968  

A randomized control trial of furosemide or placebo with usual antihypertensives in the antepartum management of 
severe hypertension with wide pulse pressure 
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9. Emergent therapy for acute-onset, severe hypertension during pregnancy and the 
postpartum period. Committee Opinion No. 692. American College of Obstetricians and 
Gynecologists. Obstet Gynecol 2017;129:e90–5. (Level III). PMID 28333820. 
 
 
 
 
 
 
Section II:  Criteria for Subject Selection 
1. Number of subjects 
List the number of subjects expected to participate.  For multi-center protocols 
include the overall projected total and site specific projected totals. 
 
This study expects to enroll 70 subjects and projects a retention rate of approximately 
80%. Fifty-six subjects are expected to complete the study. 
 
2. Demographics of subjects 
Describe the projected distribution of gender, age range, race and ethnicity of 
subjects.  Support for the inclusion or exclusion of certain vulnerable populations 
(i.e. pregnant women, minors, minorities, age groups, etc.) should be included. 
 
This study expects to enroll pregnant females at least 18 years of age and at least 20 
weeks of gestation with hypertensive disorder in pregnancy. No restrictions on race or 
ethnicity will be imposed. Since preeclampsia is a disease only encountered in 
pregnancy, and pregnant women are the only population to incur potential benefit from 
this body of evidence, it is vital that pregnant women be involved as subjects. 
 
3. Inclusion criteria  
Define subject eligibility based on scientific rationale and safety considerations. 
Include the timeframe of data collection for retrospective studies. 
 
 Inclusion Criteria 
 
• 
Subjects 18 years of age or older 
• 
Subjects with intrauterine pregnancy at or beyond 20 weeks of gestation 
• 
Subjects with a diagnosis of hypertensive disorder in pregnancy 
• 
Subjects with persistent (on repeat BP check 15 min apart) severe range blood 
pressure recordings (systolic BP³ 160 or diastolic BP³ 110) with wide pulse 
pressure (>60 mmHg) 
• 
Subject able to provide informed consent 
 
4. Exclusion criteria  
Define exclusion criteria to limit the study population and prevent subjects from 
being exposed to excess risk by the study.  Exclusion criteria should account for 
warnings, precautions, and contraindications listed in current product labeling.   
 
Exclusion Criteria 
• 
Subjects less than 18 years of age 
• 
Subjects with intrauterine pregnancy less than 20 weeks of gestation 
• 
Subjects with known fetal anomaly 
• 
Subjects with hypokalemia (K <3.0 mEq/L) on admission 

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severe hypertension with wide pulse pressure 
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• 
Subjects with anuria (<50mL urine in 24 hours) or renal failure 
• 
Subjects previously taking diuretics or potassium supplements for any reason 
• 
Subjects with a known allergy/adverse reaction to furosemide 
• 
Subjects who are unable to understand and/or sign the informed consent 
• 
Active labor (³ 6cm dilated) or epidural in place 
 
5. Vulnerable subjects  
Provide justification for the necessary inclusion of vulnerable populations.  
Vulnerable subjects often need additional protection and certain restrictions and 
requirements may apply. Children, pregnant women, and prisoner are examples of 
vulnerable populations. 
 
Preeclampsia exclusively affects pregnant individuals. As such, pregnant subjects 
should be studied. To protect these patients, consent forms will be collected and we will 
reiterate that declining study participation will in no way affect the quality of care they will 
receive.   
  
Section III:  Methods and Procedures 
1. Methods and procedures 
Summarize the research design (observational, randomized, case-study, etc.) and 
include a schematic diagram if applicable.  Provide a sequential list identifying all 
the procedures of the study, distinguishing between experimental procedures and 
procedures resulting from routine care.  Explain procedures, situations, or 
materials that may be hazardous and subsequent precautions to reduce subject 
risk.  
 
This will be a prospective double-blinded randomized placebo control trial of women ≥20 
weeks of gestation with persistent antepartum hypertension (sustained SBP ≥160 or 
DBP ≥110 mmHg) and a wide pulse pressure (>60 mmHg) who meet all inclusion criteria 
and have no exclusion criteria. It is routine that laboratory studies are performed on 
admission for all women with hypertensive disorders. If electrolyte disturbances exist, 
therapy will not be initiated unless the electrolyte is normalized or repleted. 
 
After informed consent and upon meeting inclusion criteria with severe range 
hypertension with wide pulse pressure, the study personnel will inform pharmacy 
personnel who will then randomly assigned the patient to groups by opening the next 
previously prepared sequential and numbered opaque study envelope. Participants will 
be randomized to furosemide plus an antihypertensive versus placebo containing normal 
saline and an antihypertensive. The pharmacy staff will send the assigned treatment, 
which will be administered by the bedside nurse. The vials containing the treatment will 
be indistinguishable as both furosemide and normal saline placebo are clear, colorless 
solutions. Thus, the provider, nurse, and patient will be blinded to the treatment. The 
choice of antihypertensive will be determined by the primary OB provider. At our 
institution, this will be one or more of the recommended medications for urgent blood 
pressure control as outlined by the American College of Obstetricians and Gynecologists 
Practice Bulletin on gestational hypertension and preeclampsia. These include IV 
labetalol, IV hydralazine, or immediate-release oral nifedipine. As meta-analyses have 
not shown that one of the aforementioned antihypertensives is superior than another, 
and all are reasonable options, the choice of antihypertensive will be left up to the OB 

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provider8,9. This will also improve the generalizability of the study as it does not interfere 
with what is typically done in clinical practice. 
 
As a procedure of the study, patients will have their blood pressure recorded at least 
every 15 minutes up to one hour after administration of the study drug. Thereafter, as 
part of routine care, patients in both groups will receive similar antepartum surveillance, 
including blood pressure and pulse assessment every four hours or more frequently if 
vital signs are abnormal, daily weight measurement, and daily urinary output 
measurements. 
 
Study Procedures 
 
1. Antepartum patient diagnosed with a hypertensive disorder in pregnancy. 
2. Patient approached for study participation and informed consent obtained if interested. 
3. Patient develops severe range BP (SBP>160 and/or DBP>110) with increased pulse 
pressure (>60mmHg). This will be considered baseline BP. 
4. When ordering provider's choice of antihypertensive, pharmacy notified that patient is study 
participant and randomizes patient by choosing from sequential opaque envelope.  
5. a. Patient randomized to treatment arm and receives 40mg /4mL IV furosemide in addition 
to usual antihypertensive. 
b. Patient randomized to placebo and receives 4mL normal saline in addition to usual 
antihypertensive. 
6. Blood pressure check every 15 minutes after administration of furosemide/placebo for four 
recordings (15, 30, 45, 60 minutes) 
 
 
2. Data analysis  
Specify statistical and analytical methods (statistical power, sample size, 
significance level, etc.).   
 
 
The primary outcome variable is reduction in mean systolic BP during the 1-hour period 
after drug administration. BP will be taken every 15 minutes for 1 hour and averaged. 
Intention-to-treat analysis will be performed. This study will use a two-sided t-test with 
the null hypothesis set at the standard significance level (p –value < 0.05), to determine 
if the addition of furosemide to usual antihypertensive significantly reduces blood 
pressure.   
 
Change in average BP from baseline will be tested comparing the group receiving 
furosemide and the group receiving placebo using Mann-Whitney U, as BP usually 
presents as a non-parametric continuous variable. Multivariate regression will be used to 
adjust for potential confounders, such as maternal age, BMI, diabetes, baseline BP, 
antihypertensive chosen by the primary obstetrician, number of doses of 
antihypertensive, and gestational age. Comparative testing will be done to explore 
differences between the furosemide and placebo groups. Continuous variables satisfying 
the assumption of normality will be tested using the Student t-test and means and 
standard deviations will be reported. Otherwise, variables will be tested using the Mann-
Whitney U test and will be reported using medians and interquartile ranges. The χ2 or 

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Fisher exact test will be utilized to test categorical variables and sample sizes and 
percentages will be reported.  
 
A power calculation was completed using OpenEpi, Version 3, open source calculator—
SSMean. The assumption of normality and that both groups will have the same common 
variance was applied. We set the standard deviation value as 20mmHg in the power 
calculation, which is based on pilot data from our own practice as well as data found in a 
randomized clinical trial using furosemide versus placebo (Ascarelli et al, Ob/Gyn 2005). 
A 15mmHg reduction in mean systolic blood pressure in the placebo group compared 
with the IV furosemide group was considered to be clinically significant as this 
represents an attainable, yet safe reduction from severe to mild range blood pressure. 
Using the 2-group Student t-test of equal means, 28 patients per study arm for a total of 
56 patients would be required to detect a difference of 15mmHg with 80% power and a 
significance level of p=0.05. Once data has been collected, we will test for normality and 
use the appropriate statistical tests. 
 
To account for patients who withdraw from the study or who need to be excluded after 
consent, 35 per arm or 70 total patients are to be enrolled. A randomization schedule will 
be created using block randomization with 10 blocks of 10 participants allocating 
randomization numbers to drug or placebo. The numbers will be sequentially assigned to 
participants by the pharmacist on duty. The hospital pharmacy will maintain the master 
list of the randomization log with patient study identifiers. 
 
Data monitoring 
Describe data monitoring methods for studies with more than minimal risk (i.e. 
data monitoring committee).  Explain adverse event reporting procedures.   
 
This is a greater than minimal risk study. Adverse events will be reported to the sub-
investigator and primary investigator by the nurse and/or the obstetric provider. 
Furthermore, the sub-investigator will be actively following study participants closely to 
monitor for adverse events. If found, these will be reported to the institutional review 
board according to their reporting polices. 
 
3. Data storage, security, and confidentiality 
Describe where data will be stored and how data will be secured during the study.  
Provide information on confidentiality measures (coding, storage mechanisms, 
etc.).  Indicate who will have access to the data and how the data will be used. If 
subject identifiers will be released, describe to whom and for what purpose the 
data will be released. 
 
Data will be stored on a password-protected computer and maintained for 10 years after 
study completion. The data will be recorded in Microsoft Excel and will only be 
transmitted electronically through UCERA’s encrypted email service among other study 
personnel in the same encrypted network. Access to subject data will be limited to the 
principal investigator, sub-investigators, and study staff.  Data will be de-identified when 
data collection is complete, at which time each subject will be given a subject ID number. 
A key containing subject ID numbers will be maintained by the investigator and sub-
investigator. Data will only be used for research purposes. 
 

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4. Data Sharing 
Describe plans for data sharing, particularly for publication purposes. Many 
journals now require authors to disclose how de-identified individual level data 
will be shared. Some journals require data sharing plans to be posted in a public 
registry, such as Clinicaltrials.gov. Additional information about data sharing can 
be found here: 
https://grants.nih.gov/grants/sharing_key_elements_data_sharing_plan.pdf 
https://grants.nih.gov/grants/policy/data_sharing/data_sharing_workbook.pdf 
 
 
The following statements are in response to data sharing guidelines by Elsevier. 
 
Will individual participant data be available (including data dictionaries)?  
Individual participant data will be made available.  
 
What data in particular will be shared?  
Individual participant data that underlie the results reported any future manuscript, after 
deidentification (text, tables, figures, and appendices). 
 
What other documents will be available?   
There are no plans for additional documents to be made available. 
 
When will data be available (start and end dates)?  
Beginning 9 months and ending 36 months following any publication.  
 
With whom?  
Researchers who provide a methodologically sound proposal.  
 
For what types of analyses?  
To achieve aims in the approved proposal.  
 
By what mechanism will data be made available?  
The data will be deposited to Mendeley Data, a data repository that is supported by 
Elsevier and the American Journal of Obstetrics & Gynecology. 
 
5. Transition from research participation (if applicable) 
Describe how subjects who terminate participation will be transitioned to regular 
care (such as, taper study medication, return to primary care provider). 
 
Subjects who terminate participation will resume regular care as determined by her 
primary treatment team. The investigators will discontinue collecting data on the 
individual and the choice of medications for acute blood pressure control will no longer 
be influenced by the investigators or study protocol. 
 
Section IV:  Risk/Benefit Assessment 
1. Risk category (Contact HPHRI if you need assistance determining risk level) 
State the risk of participating in the study as either Minimal or Greater than 
Minimal.  Risk is defined as the potential harm associated with the research that a 

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reasonable person would find injurious. Minimal Risk means that the probability 
or magnitude of harm or discomfort anticipated in the research are not greater 
than those ordinarily encountered in daily life or during the performance of 
routine physical or psychological examinations or tests. 
 
Participation in this study presents greater than minimal risk to subjects but not greater 
than the risks incurred by their existing disease process. As patients admitted with 
severe preeclampsia are required to have intravenous access, no additional invasive 
lines would be placed for the sole purpose of administering the study medications. 
Additionally, furosemide is already used for the aforementioned indication (severe range 
blood pressure with wide pulse pressure) in pregnant women. As furosemide is an 
approved drug being used for its approved indication in this study (ACC/AHA [Whelton 
2017], risks incurred to the patient are outweighed by the potential benefit of treating a 
life-threatening condition (severe range blood pressure). 
 
2. Potential risk(s) 
Describe any potential risks associated with the study (physical, psychological, 
sociological, economic, and/or legal).  If possible, estimate the probability of a 
given risk and potential reversibility. 
 
Potential risks associated with participation in this study include the known 
pharmacologic effect of furosemide, which include fluid/electrolyte loss as well as rare 
side effects such as.  
 
Cardiovascular: Necrotizing angiitis, orthostatic hypotension, thrombophlebitis, vasculitis 
Central nervous system: Dizziness, headache, paresthesia, restlessness, vertigo 
Dermatologic: Acute generalized exanthematous pustulosis, bullous pemphigoid, 
erythema multiforme, exfoliative dermatitis, pruritus, skin photosensitivity, skin rash, 
Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria 
Endocrine & metabolic: Glycosuria, hyperglycemia, hyperuricemia, increased serum 
cholesterol, increased serum triglycerides 
Gastrointestinal: Abdominal cramps, anorexia, constipation, diarrhea, gastric irritation, 
mouth irritation, nausea, pancreatitis, vomiting 
Genitourinary: Bladder spasm 
Hematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, eosinophilia, 
hemolytic anemia, leukopenia, purpura, thrombocytopenia 
Hepatic: Hepatic encephalopathy, intrahepatic cholestatic jaundice, liver enzymes 
increased 
Hypersensitivity: Anaphylaxis, anaphylactoid reaction, anaphylactic shock 
Immunologic: DRESS syndrome 
Neuromuscular & skeletal: Muscle spasm, weakness 
Ophthalmic: Blurred vision, xanthopsia 
Otic: Deafness, tinnitus 
Renal: Interstitial nephritis (allergic), renal disease 
Miscellaneous: Fever 
 
Source: https://www.uptodate.com/contents/furosemide-drug 
information?search=furosemide&source=panel_search_result&selectedTitle=1~148&usa
ge_type=panel&kp_tab=drug_general&display_rank=1 

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3. Protection against risk(s) 
Describe how the study will minimize or prevent any potential risks.  Techniques 
to minimize risk include subject monitoring, withdrawal criteria, and follow-up 
procedures. 
 
Subjects will be monitored for side effects and dosage levels will be adjusted if the 
subject experiences side effects from furosemide. Subjects will not receive additional 
furosemide if side effects are deemed significant. Subjects will be allowed to withdraw 
from the study at any time without consequence.  If new information about the study 
becomes available, subjects will be informed and re-consented if applicable.   
 
 
4. Potential benefit(s) to the subject 
Describe any potential medical benefit(s) for subject participation.  State if 
participation results in no benefit to the subject. 
 
The direct medical benefits to the subject for participating in the study include acute 
control of severe hypertension, which reduces the risk of stroke, placental abruption, 
hypertensive encephalopathy, and myocardial infarction. An additional benefit may 
include prolongation of pregnancy at critical gestational ages which may reduce the risks 
of prematurity which includes respiratory distress, intraventricular hemorrhage, 
necrotizing enterocolitis, and metabolic and thermic dysregulation. 
 
5. Alternative to participation 
Describe any alternative therapies or courses of action available to the subject if 
they decide not to participate in the study. 
 
Should a subject decide not to participate in the study, they will receive the standard of 
care for severe hypertension, which typically includes IV labetalol, IV hydralazine, or oral 
immediate-release nifedipine. However, furosemide is an adjunct that may be 
administered to the patient per the primary clinician’s decision, unrelated to the study. 
 
Section V:  Subject Identification, Recruitment and Consent/Assent  
(If you are requesting a waiver of consent this section can be deleted) 
1. Method of subject identification and recruitment 
Describe how subjects will be identified and recruited.  Include steps to minimize 
undue influence if recruitment includes an investigator’s students, employees, 
and/or patients. 
 
 
Contact will be initiated in person at the time of severe range blood pressure and 
meeting inclusion criteria by the antepartum care provider. If eligible, individuals who are 
involved in the study and identified as key study personnel will provide information about 
the study to the subject and if the subject is interested will proceed with obtaining 
informed consent. Subjects will be informed of the voluntary nature of the study and 
informed of alternative treatment options.   
 
2. Consent process 

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List study team members authorized to obtain consent and describe the process 
of informed consent. 
 
 
Informed consent will be primarily conducted by the sub-investigators, principal 
investigator, and trained residents and fellows who have completed the necessary 
training for research clearance. The subject will be approached with study information as 
close to the time at which she meets inclusion criteria, which in many cases will be at the 
time of admission. If the study participant is not ready to make a decision regarding their 
participation at the time of informed consent, then the study personnel will return later 
that day or the next. The informed consent process will consist of reviewing the informed 
consent documents and asking the subject a series of questions to ensure 
comprehension (see subject/representative comprehension below).   
 
3. Subject capacity (if applicable) 
Describe how capacity will be assessed and by whom.  State the anticipated 
degree of impairment relative to the subject’s ability to consent. 
 
Capacity will be assessed by the admitting provider at the time of the admission history 
and physical by directed clinical interview and exam. This includes the ability to 
understand information about treatment; the ability to appreciate how that information 
applies to their situation; the ability to reason with that information; and the ability to 
make a choice and express it. We anticipate there to be no degree of impairment relative 
to the subject’s ability to consent.  
 
4. Subject/Representative comprehension 
Describe how it will be determined that the subject /representative understood the 
information presented during the informed consent process.  If children or 
decisionally impaired adults will participate, include a plan to assess 
comprehension during the assent process. 
 
To determine comprehension of the informed consent, subjects will be asked a series of 
questions. These include: 
 
1. Can you briefly recount the purpose of the study and your involvement? 
2. What is your understanding of your decision to participate in the study, to decline 
participation, or to discontinue participation after being initially involvement and how 
this impacts the care you receive? 
3. In case you have further questions about the study or your involvement, are you 
aware that you may contact the investigators? 
   
 
5. Documentation of consent 
If not addressed in the process of consent section, explain how consent will be 
documented and where documentation will be stored. 
 
Consent will be documented on the Hawai‘i Pacific Health Research Institute IRB-
approved informed consent form and by the subinvestigator’s password-protected 
electronic log. Paper documentation will be stored by the subinvestigator in a locked-file 

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cabinet and electronic documentation will be stored on a password-protected computer. 
A copy of the signed consent form will be provided to the subject and will be scanned 
into the electronic medical record.  
 
6. Costs to the subject 
There will be no costs incurred by the subject as a result of participating in the study as 
this is part of global inpatient pregnancy care and the medications in this study are 
commonly used in the inpatient setting for the aforementioned medical indications. 
 
7. Payment for participation 
There will be no payment for participation in this study.