Torsemide for the Prevention of Persistent Postpartum Hypertension in Preeclamptic Women: A Randomized, Placebo-Control Trial
Phase: PHASE2
Conditions: Preeclampsia
Sponsor: The University of Texas Health Science Center, Houston

Viteri et.al. 
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IRB NUMBER: HSC-MS-16-0198 
IRB APPROVAL DATE: 06/23/2016 
 
 
 
 
 
 
 
 
 
 
Torsemide for the Prevention of Persistent Postpartum Hypertension in Preeclamptic 
Women: A Randomized, Placebo-Control trial 
 
 
NCT02813551 
 
Version Date: 06/23/2016 
 
 

Viteri et.al. 
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IRB NUMBER: HSC-MS-16-0198 
IRB APPROVAL DATE: 06/23/2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Torsemide for the Prevention of Persistent Postpartum Hypertension in Preeclamptic 
Women: A Randomized, Placebo-Control trial 
 
 
 
 
STUDY PROTOCOL 
 
 
 
 
Principal Investigator: Oscar A. Viteri, MD 
 
 
 
Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, The 
University of Texas Health Science Center at Houston 
 
 
 
 
 
 
 
TROPHY TRIAL 
(ToRsemide for pOstPartum HYpertension) 

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IRB NUMBER: HSC-MS-16-0198 
IRB APPROVAL DATE: 06/23/2016 
 
 
 
 
BACKGROUND AND SIGNIFICANCE 
 
Pregnancy related hypertensive disorders complicate up to 10% of pregnancies 
worldwide. Indeed, the incidence of preeclampsia has increased 15% in the United States over 
the past two decades1. While most research efforts have mostly been focused on the antenatal 
management of hypertension for maternal and fetal benefit, there is a paucity of studies 
evaluating the behavior of postpartum hypertension and the pharmacologic therapies during 
this period to optimize maternal safety and minimize hospital stay2–7. Indeed, persistent 
postpartum hypertension results in increased medical costs due to prolonged 
hospitalization, need for magnesium sulfate and antihypertensive drugs, as well as 
increased hospital readmission rates. In the long term, women with persistent hypertension 
are at increased risk for developing cardiovascular disease and kidney failure later in 
life8. 
 
The exact incidence of postpartum hypertension is difficult to ascertain since most 
women will not have their BP checked until their 6-week postpartum visit2. It is generally 
accepted that the reported prevalence of new onset hypertension-preeclampsia in the 
postpartum period ranges from 0.3-27.5%2. In 2010, a large population-based study reported 
that 0.3% of all postpartum visits to the emergency departments were due to hypertension or 
preeclampsia7. These conditions are either secondary to persistent hypertension or 
exacerbation of gestational hypertension, preeclampsia, chronic hypertension or because of a 
new onset disease2. 
 
Pathogenesis of Postpartum Hypertension 
 
In women with preeclampsia, BP usually decreases within 48 hours following delivery, 
but increases again 3-6 days postpartum. In contrast, development of de novo hypertension in 
the postpartum period, elevated BPs appear for the first time after delivery through 6-weeks 
postpartum. One study demonstrated that 44% of eclampsia cases occurred in the first 48 
hours9, and a recent large retrospective study found that 63% of patients readmitted with 
postpartum hypertension had no antecedent diagnosis of pregnancy-related hypertensive 
disorders. Regardless of the antepartum diagnosis of preeclampsia, the authors concluded 
that the risk of eclampsia was highest within 7 days after delivery10. This prompted the 
American College of Obstetricians and Gynecologists (ACOG) to recommend close 
outpatient blood pressure monitoring in all women with preeclampsia 7-10 days (or 
sooner if the patient is symptomatic) after delivery as standard of care11. 
 
It is believed that, in women with preeclampsia prior to delivery, persistent hypertension 
and edema result from mobilization from the extravascular to the intravascular space of 6-8 
liters  of  total  body  water  and  sodium  (950  mEq)  accumulated  during  pregnancy6.  The 
increased urinary sodium excretion was observed on days 3-5 postpartum, likely as a result of 
increase in atrial natriuretic peptide (ANP) and activation of the renin-angiotensin-aldosterone 
system12. However, preeclampsia and eclampsia can develop up to 4 weeks postpartum. 
Compared to women with preeclampsia, fewer women with gestational hypertension appear to 
have postpartum hypertension. Also, the duration of this hypertension appeared to be shorter 
(mean ± SD of 6 days, SD 5.5 days) that in women with preeclampsia13. 

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IRB NUMBER: HSC-MS-16-0198 
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Role of Loop Diuretics in Postpartum Hypertension 
 
Recent studies have proposed the use of loop diuretics to steepen the slope of excess 
extravascular fluid characteristic of women with preeclampsia in an effort to decrease 
hypertensive  complications  in  the  postpartum  period14,15   (Table  1).  As  the  most  effective 
diuretic class, loop diuretics inhibit the Na+-K+-2CL-  symporter at the thick ascending limb of 
the loop of Henle. This symporter captures free energy in the Na+ electrochemical gradient 
established by the basolateral Na+ pump and provides for an uphill transport of K+ and Cl+ into 
the cell. K+ channels in the luminal membrane provide a conductive pathway for K+ recycling. 
Hyperpolarization of the luminal and depolarization of the basolateral membranes result in a 
transepithelial potential difference of 10 mV (lumen positive relative to the interstitial space), 
due to the presence of Cl-  ions. This lumen positive potential repels cations (Na+, Ca2+  and 
Mg2+) and provides an important driving force for the paracellular flux of these cations into the 
interstitial space. Loop diuretics block the function of the luminal symporter bringing salt 
transport in this segment to a virtual standstill. The same remains true for other cations. 
Increased luminal concentrations of Na+ further depolarize de luminal membrane and therefore 
enhance the negative voltage gradient, which facilitates K+ excretion. Finally, activation of the 
renin-angiotensin-aldosterone axis also contributes to K+ and H+ excretion. Notably, this 
phenomenon  is  less  pronounced  with  Torsemide,  which  antagonizes  the  aldosterone 
receptor16. Table 2 depicts the pharmacokinetic characteristics of loop diuretics available in the 
US. Pharmacodynamic properties are depicted in Table 3. 
 
Table 1. Studies on Loop Diuretics for the Prevention of Postpartum Hypertension 
 
Study 
Inclusion Criteria 
Intervention 
Control 
Primary Outcome 
Mathews 
1997 
RCT 
(n=19) 
Postpartum women with 
severe preeclampsia before 
delivery 
Furosemide: 
40 mg/d x 7d 
Placebo 
Fall in mean MAP (NS) 
Need for antihypertensive (NS) 
Mean Length of Stay (NS) 
Ascarelli 
2005 
RCT 
(n=264) 
Postpartum women with 
preeclampsia or 
superimposed preeclampsia 
before delivery 
Furosemide: 
20 mg/d x 5d 
KCl: 
20 mEq/d x 
5d 
N/A 
Mean postpartum BP 
142±13 vs 153±19 mmHg P<0.004 
for severe disease only 
Antihypertensive at D/C 
6% vs 26% P = 0.045 for severe 
disease only 
Tuuli 
2015 
RCT 
(n=248) 
Postpartum women with 
gestational hypertension, 
preeclampsia and severe 
preeclampsia before delivery 
Furosemide: 
40 mg/d x 6d 
KCl: 
20 mEq/d x 
6d 
Placebo 
CMM 0-6 wks postpartum 
- Antihypertensive at D/C 
- Readmission for hypertension 
- End organ damage 
Currently recruiting 
Figueira 
2015 
RCT 
(n=120) 
Postpartum women with 
preeclampsia before delivery 
Furosemide: 
20 mg/d x 5d 
Placebo 
Mean postpartum BP (from 24 h 
to 15 days after delivery) 
Enrollment completed 
Abbreviations: RCT = randomized controlled trial, MAP = mean arterial pressure, NS = not significant, BP = blood pressure, 
D/C = discharge, CMM = composite maternal morbidity 

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IRB NUMBER: HSC-MS-16-0198 
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Table 2. Pharmacokinetic Properties of Loop Diuretics 
 
Property 
Furosemide 
Bumetanide 
Torsemide 
Relative potency 
1 
40 
3 
Affected by food 
Yes 
Yes 
No 
Bioavailability (%) 
10-100% (avg. 50) 
80-100 
80-100 
Onset of action (min) 
30-60 
30-60 
30-60 
Metabolism 
65% renal 
62% renal 
80% hepatic 
Half-life (h) 
1.5-2 
1 
3-4 
Dosing (mg) 
20-80 BID-TID 
0.5-2 QD-BID 
10-20 QD 
Cost (US $)/100 tab 
40 mg (100): $16.8 
1 mg (100): $87.3 
10 mg (100): $70.3 
Abbreviations: QD = daily, BID = twice daily, TID = three times a day 
 
 
Table 3. Pharmacodynamic Properties of Loop Diuretics 
 
Property 
Furosemide 
Bumetanide 
Torsemide 
Lactation 
Excreted 
(pregnancy category C) 
No data 
(pregnancy category C) 
No data 
(pregnancy category B) 
Effect on RAA system 
None 
None 
Inhibits 
Cardiac effects 
None 
None 
Improved LVED and LVES 
volumes,  BNP and cardiac 
remodeling 
Rebound Na 
retention* 


None 
Potassium loss 



Magnesium loss 



Calcium loss 



Quality of Life** 



* Suboptimal dosing (i.e. once a day) of furosemide results in rebound Na+ retention, decreasing diuretic effect. 
** Torsemide is associated with less urgency and sensation of incomplete voiding than Furosemide or Bumetanide. 
Abbreviations: RAA = renin-angiotensin-aldosterone system, LVED = left ventricular end-diastolic, LVES = left ventricular end- 
systolic, BNP = brain natriuretic peptide 
 
Although diuretics are generally considered as second-line agents for the treatment of 
hypertension in pregnancy11, is not known whether or not antihypertensive or diuretic therapy 
should be routinely instituted postpartum in women with antenatal preeclampsia in order to 
prevent postpartum hypertension6. An observational study of 67 women with preeclampsia 
found that 50% of women had a blood pressure greater than 150/100 mmHg on day 5 
postpartum17. In a small randomized clinical trial (N = 19), postpartum women with 
preeclampsia and severe features before delivery received Furosemide 40 mg daily for 7 days 

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IRB NUMBER: HSC-MS-16-0198 
IRB APPROVAL DATE: 06/23/2016 
 
 
 
 
and were compared against placebo. No differences were noted in the mean and maximum 
blood pressure, need for antihypertensive treatment and mean length of hospital stay14. 
Conversely, in the no treatment arm of a larger randomized clinical trial (N = 264) comparing 
Furosemide 20 mg daily for 5 days with no intervention, 26% of women with preeclampsia 
were observed to require antihypertensive therapy at the time of hospital discharge (versus 6% 
in the Furosemide group)15. Notably, all these studies dosed Furosemide once daily. 
 
Rationale for a Clinical Trial and Hypothesis 
 
The evidence on the role of loop diuretics for the prevention of persistent postpartum 
hypertension is promising but limited. ACOG recognizes that the optimal use of diuretics in 
the puerperium in patients with preeclampsia, eclampsia and hemolysis, elevated liver 
enzymes and low platelets (HELLP) syndrome requires further study and clarification to 
augment current management schemes11. Experience with Furosemide in the postpartum 
period has been favorable, but given its low potency, unpredictable bioavailability and 
suboptimal dosing with potential for rebound sodium retention, it may not be an 
adequate drug for first-line prophylaxis for persistent postpartum hypertension. 
 
There  is  no  data  available  on  the  use  of  Torsemide  in  the  puerperium.  Growing 
evidence suggests the superior effect and safety profile of Torsemide when compared to 
Furosemide and Bumetanide in the management of edematous states, particularly given its 
higher potency, cardioprotective effects and more predictable bioavailability18. 
 
We hypothesize that in postpartum women with preeclampsia prior to or immediately 
after delivery, oral Torsemide (20 mg daily for 5 days) will reduce the rate of persistent 
postpartum hypertension requiring new or increased antihypertensive medications. 
 
RESEARCH DESIGN & METHODS 
 
Population 
 
Puerperal women within the first 24 hours after delivery. 
 
Primary Outcome 
 
Persistent 
postpartum 
hypertension 
requiring 
new 
or 
increased 
doses 
of 
antihypertensive medications at the time of hospital discharge (SBP ≥ 150 and/or DBP ≥ 
100 mmHg, on 2 separate occasions, at least 4 hours apart). 
 
Secondary Outcomes 
 
- 
Occurrence of severe postpartum hypertension (SBP≥160 and/or DBP≥110 mmHg on 2 
occasions, 15 minutes apart) 
- 
Need for postpartum readmission 
- 
Length of hospital stay after delivery 
- 
Weight change (from randomization to discharge) 

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IRB NUMBER: HSC-MS-16-0198 
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- 
Changes in lower-extremity edema (from randomization to discharge) 
- 
Incidence of persistent postpartum hypertension 7-10 days after delivery and 6 weeks 
postpartum (SBP ≥ 140 and/or DBP ≥ 90 mmHg) 
- 
Side effects of therapy: 
o Hypokalemia 
o Failure to establish lactation 
- 
Severe composite maternal morbidity: 
o Need for ICU admission 
o HELLP 
o Eclampsia 
o Stroke 
o Renal failure 
o Pulmonary edema 
o Cardiomyopathy 
o Maternal death 
 
Ancillary Studies 
 
It is not known whether Torsemide is excreted in breast milk. Prior to hospital discharge, 
we plan to collect a small sample of breast milk (3.5 mL) to measure the concentration of this 
medication in the breast milk, and 10 mL of maternal blood for serologic measurement of 
Torsemide concentrations as well as electrolyte profile. 
 
Study Design 
 
Randomized, double-masked, placebo-controlled trial. 
 
Inclusion Criteria 
 
 Postpartum women at ≥ 18 years of age 
 Antepartum/intrapartum or within 24 hours postpartum diagnosis of either: 
o Preeclampsia 
o Preeclampsia with severe features 
o Preeclampsia superimposed to chronic hypertension 
 
Exclusion Criteria 
 
 Chronic hypertension without superimposed preeclampsia 
 Gestational hypertension 
 Urine output < 30 cc/h at time of randomization 
 Heart failure or pulmonary edema 
 Hypersensitivity to Torsemide or sulfonylureas 
 Hypokalemia (serum potassium < 3 mEq/L) 
 Preexisting diuretic use within 24 hours prior to randomization 

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IRB NUMBER: HSC-MS-16-0198 
IRB APPROVAL DATE: 06/23/2016 
 
 
 
 
Recruitment 
 
Recruitment will occur on the Labor and Delivery ward at Memorial Hermann Hospital- 
Texas Medical Center. 
 
Randomization 
 
Central  randomization  will  be  conducted  by  Investigational  Drug  Service  (IDS) 
pharmacy at Memorial Hermann Hospital-Texas Medical Center.  Only the IDS pharmacy and 
study statistician will know the sequence of randomization.   The subject will be randomized 
either to oral Torsemide 20 mg daily for 5 days or oral placebo daily for 5 days. If the patient is 
discharged before postpartum day 5, she will be given the study medication to take at home 
and complete 5 days. 
 
Interventions and Procedures 
 
Written informed consent will be obtained from participating women  in the hospital 
setting only. Permuted block randomization with a random fashion will be used to prevent 
imbalances  between  groups.  Study  medications  will  be  placed  in  sequentially  numbered 
sealed opaque envelopes. Each envelope will contain a package containing either Torsemide 
tablets 20 mg or placebo tablets. An investigator who will administer the drugs will open these 
envelopes. Torsemide and placebo tablets will be identical. Both provider and participant will 
be  blinded  regarding  the  treatment  administered.  Women  randomized  to  Torsemide  will 
receive the medication once daily starting within 24 hours after delivery. Torsemide will be 
continued daily for a total of 5  days. The administration of placebo will follow the same 
protocol. Potassium supplementation will not be required since normally Torsemide is not 
associated with a significant degree of hypokalemia. 
 
Blood pressure measurements for the primary outcome will be performed using a single 
pre-specified sphingomanometer at 3 time points: at randomization and at day 5 (or at 
discharge, whichever occurs first). If the BP on day 5 (or when patient is discharged) is 
between 150/100 mmHg and 170/110 mmHg, a second BP will be obtained within 4 hours 
(unless BP at any time after delivery was ≥ 150/100, in which case the subject will be 
considered a positive outcome).  If BP is ≥ 170/110 mmHg, a new BP will be taken within 15 
minutes. If persistent, the patient will be considered to have severe hypertension and will be 
managed as per unit protocol. In this case, the subject will also be considered as a positive 
outcome. If the criteria for persistent postpartum hypertension are met, the choice of 
antihypertensive medication, route and dosage will be left to the discretion of the treating 
physician. 
 
Blood pressure measurements for secondary outcomes will be performed as per 
standard of care in the outpatient setting at 7-10 days after delivery (or pre-specified 
sphingomanometer if patient remains hospitalized) and at the 6-week postpartum visit. 
 
Peripheral edema will be assessed by measuring the ankle circumference using a 
validated standardized technique to minimize errors19. A circumferential mark will be made with 
an indelible black marker 5 cm proximal to the right medial malleolus to ensure a consistent 

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IRB NUMBER: HSC-MS-16-0198 
IRB APPROVAL DATE: 06/23/2016 
 
 
 
 
location of measurements. A measuring tape will be placed such that is upper edge is in 
contact with the circumferential mark. Baseline circumferential ankle measurements will be 
made at 2 time points: at randomization and at day 5 (or at discharge, whichever occurs first). 
 
Maternal weight change will be assessed using a single pre-specified weight scale at 
the time of randomization and at day 5 (or at discharge whichever occurs first). 
 
In addition, 3 mL of maternal breast milk will be collected 44-48 h after the initial dose of 
Torsemide to measure the concentrations of the study drug, and 10 mL of maternal blood will 
be collected for serologic measurement of Torsemide concentrations as well as electrolyte 
profile. A baseline sample of 10 mL of maternal blood will also be collected at the time of 
hospital admission (as part of routine admission labs) and 44-48 h after the initial dose for 
metabolic profile. Samples will be stored at -20o Celsius for pharmacokinetic analysis. 
 
Sample Size 
 
Data from Walters et.al.17 and Goel et.al.20 showed that 50% of women diagnosed with 
preeclampsia (but not gestational hypertension) prior to delivery have persistent postpartum 
hypertension requiring treatment 5 days after delivery (i.e. BP ≥150/100). To detect a 50% 
reduction in this rate, with 80% power and alpha-error of 0.05, a total of 118 (59 in each arm) 
patients need to be randomized. A total of 250 women would need to be approached for 
consent to accommodate an expected enrollment rate of 50%. 
 
At MHH and LBJ hospitals, there are 7132 deliveries per year as of 2013. Assuming a 
10% rate of antepartum preeclampsia, there would be >700 women per year eligible.  If we 
anticipate a 50% enrollment rate, then we should be able to complete this study in 1 year. 
 
Statistical Tests 
 
An intent-to-treat and/or per protocol analysis will be conducted. The rate of the primary 
outcome, persistent postpartum hypertension, will be compared between the intervention and 
control group using a log binomial (or Poisson in case of non-convergence) model to estimate 
relative risk and 95% confidence interval (CI). Each secondary outcome will be similarly 
analyzed  using  the  best  fitting  generalized  linear  model  with  intervention  group  as  the 
covariate. For all outcomes, we will report relative risks or differences and 95% CIs. 
 
We will also conduct an interim Bayesian analysis of the primary outcome when 50% of 
enrollment has occurred to calculate probability of treatment benefit or harm. We will use a 
neutral prior distribution for the intervention effect that excludes implausible large treatment 
effects: Normal (0, SD=0.70) in the log RR scale (prior 95% interval for the RR of 0.23-4.35)21 
 
Safety Assessment 
 
Torsemide is generally well tolerated and adverse reactions are rare. In general, loop 
diuretics as a class may lead to profound diuresis and fluid electrolyte imbalances. This is 
particularly significant when the medication is administered intravenously or for long periods of 
time, with increased risk of symptomatic hypokalemia among patients treated with Furosemide. 

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However, in randomized clinical trials, hypertensive patients receiving Torsemide for 1 year 
had a mean decrease in serum potassium of approximately 0.1 mEq/L. The percentage of 
patients who had serum potassium level below 3.5 mEq/L at any time during the studies was 
similar between those receiving Torsemide (1.5%) than those receiving placebo (3%)21,22. 
 
Oral administration of Torsemide has been shown in controlled studies to lower both 
systolic and diastolic blood pressure. There is however, no significant orthostatic effect, and 
there is only a minimal peak-through difference in blood pressure reduction. The 
antihypertensive effects of Torsemide are greater in the African-Americans (a low-renin 
population). It has also been administered in conjunction with other antihypertensives (i.e. β- 
adrenergic blocking agents, ACE inhibitors, and calcium channel blockers). Adverse drug 
interactions have not been observed, and special dose adjustment has not been necessary22. 
 
Torsemide is contraindicated in patients allergic to sulfonylureas and those who are 
anuric22. 
 
There is no available data on the effect of Torsemide in lactation and it is not know 
whether Torsemide is excreted into the breast milk. Conversely, given that it is the only 
category B (animal reproduction studies have failed to demonstrate a risk to the fetus and 
there  are  no  adequate  or  well-controlled  studies  in  pregnant  women)  loop  diuretic  in 
pregnancy, the American Academy of Pediatrics labels Torsemide as “potentially safe in 
breastfeeding”. Indeed, both Furosemide and Bumetanide are category C (animal reproductive 
studies have shown an adverse effect on the fetus and there are no adequate and well- 
controlled studies in humans, but potential benefits may warrant use of the drug in pregnant 
women despite potential risks). However, given that loop diuretics as a class have the theoretic 
potential to suppress lactation, close monitoring is recommended23. 
 
Blood Draw with Venipuncture 
 
Blood draws will be obtained from the maternal veins once during the study.  Possible 
side effects of obtaining blood samples are pain, bruising, bleeding or infection at the blood 
drawing site and rarely, nausea or a lightheaded feeling.  A skilled nurse will be retrieving the 
maternal blood.  A maximum of 2 tablespoons of blood will be obtained at each timepoint. 
 
Breast milk sampling 
 
There are no known potential risks associated with sampling human breast milk. 
 
Budget 
 
Funding  will  be  provided  by  the  Division  of  Maternal-Fetal  Medicine,  from  the 
Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Texas 
Health Science Center at Houston ||||||||||||||||||||||||||||||||||||||||  |||||||||||||||||||||||||||||||||||||||| 
|||||||||||||||||||||||  |||||||||||||||||||||||. Projected study costs are depicted in Table 4. 

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Informed Consent 
 
A copy of the informed consent document in both English and Spanish to be used will 
be submitted by the Principal Investigator (PI) to the Institutional Review Board (IRB) for 
review and approval prior to the start of the study. A properly executed written informed 
consent shall be obtained from each patient prior to entering the study. All prospective study 
candidates will be given a full explanation of the consent form, allowed to read the approved 
form, and be provided the opportunity to ask any questions. Once all questions have been 
answered and the Investigator is assured that the individual understands the requirements of 
the study, the subject will be asked to sign the consent. The Investigator shall provide a copy 
of the signed and dated informed consent to the patient and the original shall be maintained in 
the patient’s study files. Patients who do not sign the consent form will not be permitted to 
participate in the study. 
 
Table 4. TROPHY Trial Budget 
 
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Institutional Review Board 
 
Before initiation of the study, the PI will obtain approval of the research protocol from 
the IRB. The study will be registered in  www.clinicaltrials.gov as required by US law for public 
access. 

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Specification of Safety Parameters 
 
The  TROPHY  trial  is  intended  to  evaluate  whether  the  use  of  a  loop  diuretic 
(Torsemide) in the postpartum is effective in preventing persistent hypertension of ≥ 150/100 
mmHg 7-10 days after delivery in women with preeclampsia prior to delivery. Torsemide has 
been approved by the Food and Drug Administration (FDA) for the management of 
hypertension  either  alone  or  in  combination  with  other  antihypertensives.  Torsemide  is 
routinely indicated for the treatment of edematous estates. 
 
The PI, who will also determine the safety parameters, will carefully monitor patient 
safety. The PI or designee will notify the IRB of applicable events according to institutional 
guidelines. 
 
Management of Adverse Events 
 
Any adverse events will be reported to the Committee for the Protection of Human 
Subjects (CPHS). The need for a Data Safety Monitoring Board will be deferred to the IRB. 
 
Procedures in the Event of Abnormal Clinical Findings 
 
In the event of an abnormal clinical finding, the health care provider caring for the 
participant will be notified to allow treatment in the usual clinical manner. 
 
Subject Confidentiality 
 
Each study’s subject anonymity will be maintained throughout the study. Prior to 
collection of the data a unique study number will be assigned to each case thus de-identifying 
the individual subject. Each study site will maintain a log of the study subject to the assigned 
study number. 

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Figure 1. Study design and population 

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IRB APPROVAL DATE: 06/23/2016 
 
 
 
 
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