Rezum First in Man Feasibility Study for the Treatment of BPH With the Rezum System
Phase: NA
Conditions: Benign Prostatic Hyperplasia, Adenoma, Prostatic, Prostatic Adenoma, Prostatic Hyperplasia, Benign, Prostatic Hypertrophy, Prostatic Hypertrophy, Benign, Rezum
Sponsor: Boston Scientific Corporation



 
 
 
1633-001 
Rev 03 
 
Protocol, Rezūm System First-In-Man Minimally Invasive 
Treatment of BPH  
(Rezūm FIM Clinical Study) 
 
 
 
 
 
 
 
 
 
 
 
 
Approvals:  Signatures on File 
Authored by: 
Sew-Wah Tay, PhD 
 
 
 
Consultant,  
Libra Medical 
Signature 
Date 
 
 
 
 
Approved 
by: 
Michael Hoey, PhD 
 
 
 
Chief Technical Officer 
Signature  
Date 
 
 
 
 
 
J. Robert Paulson Jr 
 
 
 
Chief Executive Officer 
Signature  
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Revision History 
Rev 
Date 
Description  
Comments 
01 
November 
20, 2011 
Initial Release 
 
02 
February 
24, 2012 
Added MSHQ-EjD Short Form, updated exclusion criteria for 
Phase 1, updated inclusion criteria for phase 2, updated AE 
description for LUTS and catheterization, updated CRF 
requirements, added references, updated MRI requirements,  
 
03 
March 9, 
2012 
Updated sample size for Phase 1 and Phase 2, updated water 
flow setting. 
 
 
 
 
 
 
 

 
 
 
Rezūm FIM: First In Man Feasibility Study for the Treatment of BPH with 
Rezūm System 
 
Protocol # 1633-001 
Revision 03 
March 9, 2012 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sponsor: 
NxThera Inc. 
4186 Lexington Avenue North 
Shoreview MN  55126 
Tel:  651.484.0219 
Fax:  651.484.0319 
 

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PROTOCOL SIGNATURE PAGE 
 
Rezūm FIM: First In Man Feasibility Study for the Treatment of BPH with 
Rezūm System 
 
Protocol # 1633-001 
Revision 03 
 
 
 
 
 
      March 9, 2012 
 
 
 
 
 
 
 
I have read this protocol and agree to adhere to the requirements.  I will provide copies of 
this protocol and all pertinent information to the study personnel under my supervision and 
my hospital ethics committee (EC).  I will discuss this material with them and ensure they are 
fully informed regarding the study device and the conduct of the study according to this 
protocol, applicable laws, and applicable regulatory requirements including 21 CFR parts 50, 
and 56 and hospital EC requirements. 
 
 
 
Clinical Site Name:  
 
Centro Medicao Dr. Canela D.R. 
Av Lertertad No. 44 
La Romana, Dominican Republic 
 
 
 
___________________________________________ 
 
 
Printed Name 
 
 
___________________________________________ 
 
______________________ 
Signature 
 
 
 
 
 
 
 
 
Date 
 
 
 

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Protocol Summary 
 
Title: 
In vivo treatment with NxThera Rezūm device for acute 
and urinary retention with BPH 
Purpose: 
To evaluate the effect of the NxThera BPH Rezūm System on 
prostate tissue in subjects suffering from LUTS symptoms secondary 
to benign prostatic hyperplasia (BPH).  
 
Study Design:  
This study is a single center study.  It will be carried out in two 
phases on subjects with benign prostatic hyperplasia. 
Phase 1: Acute study - In-vivo treatment of the prostate in 
subjects scheduled to have a surgical TURP or full excision of 
the prostate.  Prostate tissue will be excised after treatment as 
part of the planned surgery.  There is no follow up. 
 
Phase 2: Optimization study - Subjects with BPH symptoms 
will be treated with the Rezūm device with a range of thermal 
energies (as measured by calorie output) to optimize the 
setting for maximum lesion size with minimal intra and post 
procedure discomfort.  The lesion size and ablated tissue 
resorption rate will be followed post-procedure via MRIs. 
 
Enrollment: 
Phase 1: Up to 20 BPH subjects scheduled for surgical removal of the 
BPH tissue 
Phase 2: Up to 15 BPH subjects suffering from BPH symptoms. 
Target Subject 
Population: 
 
Male subjects > 45 years of age who have symptomatic / 
obstructive symptoms secondary to BPH requiring surgical 
intervention. 
Follow-up: 
Phase 1 – Acute, no follow up 
Phase 2 – 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 
and annually thereafter up to 5 years. 
Phase 1 
Endpoint  
Lesion size and characteristics as evaluated using Tetrazolium 
Chloride (TTC) stain and histopathologic evaluation of 
representative samples.   
Phase 2 
Endpoints 
Lesion characterization via MRI 
Intra and  post procedure discomfort 
Catheterization post procedure 
The change (improvement) from baseline in International 
Prostate Symptom Scores (IPSS) at day 1, week 1, month 1, 
months 3,6 and 12, and annually thereafter up to 5 years 
 

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Study and Data 
Management: 
Libra Medical, Inc. 
8401 73rd Ave N, Suite 63 
Minneapolis, MN 55428 
Tel: 763-477-5606 
Fax: 763-477-6357 
Email: swtay@libramed.com 
 
Study Monitors: 
Libra Medical, Inc. 
8401 73rd Ave N, Suite 63 
Minneapolis, MN 55428 
Tel: 763-477-5606 
Fax: 763-477-6357 
Email: swtay@libramed.com 
 
Sponsor: 
NxThera Inc 
4186 Lexington Ave. N. 
St. Paul, MN 55126 
(651) 484-6095 
 
 
 
 

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TABLE OF CONTENTS 
1 
BACKGROUND ................................................................................................................................................. 8 
2 
SUMMARY DEVICE DESCRIPTION ............................................................................................................ 8 
3 
SUMMARY OF PROCEDURE ........................................................................................................................ 9 
4 
PHASE I ACUTE STUDY DESIGN............................................................................................................... 12 
5 
PHASE 2: OPTIMIZATION STUDY ............................................................................................................ 13 
6 
STUDY PROCEDURES .................................................................................................................................. 15 
7 
ADVERSE EVENTS ........................................................................................................................................ 20 
8 
TRAINING ........................................................................................................................................................ 25 
9 
DEVICE MALFUNCTIONS ........................................................................................................................... 25 
10 
STUDY MANAGEMENT ............................................................................................................................... 25 
11 
REGULATORY RESPONSIBILITIES ......................................................................................................... 26 
12 
MONITORING PROCEDURES .................................................................................................................... 28 
13 
REPORTS AND RECORDS ........................................................................................................................... 28 
14 
OTHER STUDY ELEMENTS ........................................................................................................................ 29 
15 
REFERENCES ................................................................................................................................................. 33 
 
 
 
 
 
 
 

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1 BACKGROUND 
NxThera has completed more than 60 canine studies as part of its convective vapor ablation 
system product development program.  Collectively, these studies are best classified as a 
series of investigational studies that were an integral part of the Company’s efforts to develop 
and validate the safety of the system and the treatment of the prostate with vapor therapy, 
and to optimize the therapeutic delivery of vapor to effectively treat benign prostatic 
hyperplasia (BPH).   
 
An earlier version of the Rezūm System has been tested in human subjects.  This initial study 
included four acute subjects and 9 chronic subjects with up to 6 months follow-up and a 
subset of these chronic patients with 12 month follow-up data.  This study repeats the same 
study but using the revised Rezūm System that is intended for commercial use.  
 
2 SUMMARY DEVICE DESCRIPTION 
The NxThera BPH Rezūm System consists of the following components: 
 Power Generator  
 Delivery Device (which includes an insulated introducer sheath and vapor delivery 
needle) 
 Water delivery system 
 Saline flush tubing 
 
 
 
 
Figure 2-1: Rezūm System (not drawn to scale) 
 
The NxThera BPH Rezūm System consists of a RF power Generator unit which controls the 
generation and temperature of the water vapor created at the Delivery Device and delivered 
to the prostate. 
 
Within the Delivery Device is an insulated shaft with two lumens, one of which is used for a 4 
mm cystoscopy optical lens.  The other lumen contains the vapor delivery plastic needle.  At 

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the distal end of the vapor needle, the vapor emitter holes are arranged circumferentially 
around the needle through which water vapor is delivered to the prostate when the needle is 
inserted within the prostate.   
 
The Rezūm Generator system has been built in compliance with quality control system (IEC 
60601-1) and both the hardware and software of the system have gone through verification 
and validation testing, including controlling the vapor delivery. 
 
The procedure utilizes a transurethral approach under direct visualization using the optics 
from a standard rigid cystoscope which is inserted into the Delivery Device to allow the 
treating physician to visualize access to the prostate through the urethra, and to facilitate 
proper placement of the vapor needle into the prostate to deliver the vapor therapy.  Using 
the bladder neck and veru montanum as the anatomical guides (e.g., the transition zone of 
the prostate), the tip of the Delivery Device is positioned against the wall of the urethra; the 
physician then releases the safety and deploys the vapor needle into the prostate. 
 
Once the needle is fully deployed, the vapor treatment button is activated to deliver the 
water vapor for up to 10 seconds of treatment.  This process is repeated as many times as 
needed for each lobe of the prostate, with the first treatments delivered near the bladder 
neck.  The standard treatment algorithm is to leave approximately 1 cm between each 
treatment injection, and a typical sized prostate with BPH will need three 10-second 
treatments in each lateral lobe.  The median lobe, if present, may be treated with one or two 
treatments. 
 
Potential benefits of this treatment, in contrast with other transurethral ablation treatments, 
are: 
 
 No electromagnetic energy is delivered within the body.   
 Each treatment is up to 10 seconds; each lateral prostate lobe may receive 2-4 
treatments or one treatment per 1 cm length of urethra within the prostate 
 Median lobes of all sizes can be treated. 
 Treatments may be done with no or minimal local anesthesia. 
 There may be less bleeding, post procedure, than with other treatments. 
 Symptom relief is expected within days of treatment. 
 
3 SUMMARY OF PROCEDURE 
1. 
Insert the 4 mm optical lens of a rigid endoscope into the Delivery Device; 
2. 
Evaluate the Rezūm system readiness by doing a test treatment in air; 
3. 
Lubricate the shaft of the Delivery Device with Lidocaine gel or equivalent; 
4. 
Insert the shaft of the Delivery Device into the urethra until the tip is in the 
bladder using the endoscopy view to guide the Delivery Device; 
5. 
Withdraw the tip of the Delivery Device to just below the bladder neck; 
6. 
Press the tip of the shaft against the urethra, and press the flush button as 
necessary to visualize placement;   

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7. 
Depress the trigger to deploy the vapor needle into the prostate tissue.  Ensure 
that the indicator mark on the vapor needle is fully inserted into the prostate 
8. 
Pull the vapor trigger to deliver the vapor therapy.  The power will be 
automatically shut off after 10 seconds (or earlier if the vapor trigger is 
released prior to 10 seconds). 
9. 
Retract the vapor needle; 
10. 
Reposition the tip of the Delivery Device 1 cm from the first treatment 
position; 
11. 
Repeat the process with the contralateral lobe and the median lobe (if present).  
See Figure 3-3 as an illustration of the final results 
 
 
 
 
Figure 3-1: Vapor Delivered Through Vapor Needle 
 

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Figure 3-2: Prostatic Urethra After 3 Treatments on the Left Lobe 
 
 
 
 
Figure 3-3: Schematic of Ablation Zone After Treatment 
 
 
 

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4 PHASE I ACUTE STUDY DESIGN 
This study will be conducted in two phases.  The phases will run consecutively.  Both phases 
are part of a single arm, single center study.   
4.1 
PHASE 1: ACUTE STUDY 
The subjects will undergo a Rezūm procedure per the IFU with the Delivery Device inserted 
transurethrally in order to deliver the therapy directly into the prostate.  The treatment 
setting used will be based on the results obtained from treating extirpated prostate tissue 
from Rezūm Ex study.  After vapor ablation, the planned prostatectomy/adenectomy surgical 
procedure will continue until completion.  Information regarding usability, treatment 
settings, and correlation to the lesion size will be collected from an examination of the 
extirpated tissue.  The lesions from the extirpated prostate tissue will be necropsied and 
evaluated for lesion characteristics to gain additional information to optimize the vapor 
ablation treatment.    
 
4.1.1 Acute: Inclusion Criteria 
1. 
Male subjects > 45 years of age who have symptomatic / obstructive symptoms 
secondary to BPH requiring invasive intervention. 
2. 
Scheduled to have prostatic tissue surgically removed. 
4.1.2 Acute: Exclusion Criteria  
1. Presence of a penile implant; 
2. Any prior minimally invasive intervention (e.g. TUNA, Microwave) or surgical 
intervention to treat the symptoms of BPH; 
3. Confirmed or suspected malignancy of prostate; 
4. Previous pelvic irradiation or radical pelvic surgery; 
5. Urethral strictures, bladder neck contracture or muscle spasms; or, 
6. Biopsy of prostate within 30 days prior to the date of this procedure. 
7. Unable or unwilling to sign the Informed Consent Form 
4.2 
TREATMENT MEDICATION 
There are no treatment medication requirements for this portion of this study.  Medication 
will be administered at the discretion of the Principal Investigator or his designee per the 
standard hospital procedure for adenectomy.  . 
4.3 
SAMPLE SIZE 
Up to 20 BPH subjects scheduled for surgical removal of BPH tissue 
4.4 
STUDY DURATION  
There is no follow up for this acute study.  Therefore, study duration is anticipated to be no 
more than 2 weeks. 
4.5 
ENDPOINT 
Lesion size from the vapor treatment, as measured by TTC stain in the extirpated tissue. 
 

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5 PHASE 2: OPTIMIZATION STUDY 
5.1 
STUDY OBJECTIVE 
The objectives of the Phase 2 study are: 
Optimize the effectiveness of the BPH Rezūm System and assess the effect of 
treatments with different caloric values, including an assessment of subject comfort 
during the procedure and post-procedure 
Further document the safety and post-operative effects of the Rezūm System in the 
treatment of obstructive BPH. 
5.2 
 STUDY DESIGN 
In this Phase 2 study, up to 15 subjects with LUTS secondary to BPH requiring surgical 
treatment will be treated with the Rezūm System.  Treatment is ≤ 10 seconds per treatment.  
The power and water flow rate settings may be adjusted slightly to minimize pain and 
swelling to the subjects while maximizing the treatment area (e.g., lesion size).  The power 
setting will be between 175W and 250W with a concomitant adjustment to the water flow 
rate of 2.7 ml/min to 5.0 ml/min.  The actual power output will be recorded.  For all the 
treatment settings, adverse and subject responses will be collected.  The range of acceptable 
power setting have been determined in bench-top, animal studies, testing on extirpated 
human prostate to create lesions of a size that is adequate to treat the BPH tissue.  The 
unknown factor that will be evaluated in this Phase 2 study is the acute response(s) to the 
different treatments in terms of procedural and post procedural discomfort.  If the subjects 
are able to tolerate the higher caloric treatments, those treatments will be used in subsequent 
subjects.  If the subjects are not able to tolerate a particular caloric treatment, the lower 
caloric treatment will be used in subsequent subjects.   
 
 
The standard Rezūm treatment following the IFU will be followed.  Information regarding 
the vapor needle configuration, treatment settings, treatment medications, pain or discomfort 
during treatment, post-treatment catheterization requirements, and the type and severity of 
any short term irritative or urinary obstructive symptoms will be collected.  Information 
regarding the subjects’ symptomatic response and uroflowmetry characteristics will be 
collected at baseline and in follow-up evaluations conducted with each subject.  Any adverse 
events will be evaluated at each visit.  Lesion characteristics and treated tissue resorption 
rate will be measured by gadolinium enhanced MRI imaging techniques performed post-
procedure at specified intervals. 
5.3 
OPTIMIZATION ENDPOINTS 
5.3.1 Endpoint 1: Intra-procedure Pain 
Procedural pain will be assessed using the Wong Baker scale.  Subjects will be asked to rate 
the level of pain and discomfort during the treatment. 
5.3.2 Endpoint 2: Post-Procedure Catheterization  
All subjects will be kept at the clinic for observation for 24 hours post-procedure.  Post 
procedure catheterization will only be allowed if the Principal Investigator determines that 

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the subject has symptoms of retention (defined as failure to void within 8 hours post 
procedure) or requires catheterization for other safety reasons. 
5.3.3 Endpoint 3: Lesion size, as measured by MRI at Week 1 post-procedure. 
5.3.4 Endpoint 4: Change in IPSS score from baseline at various points post-procedure. 
5.4 
INCLUSION CRITERIA 
1. Male subjects > 45 years of age who have symptomatic / obstructive symptoms 
secondary to BPH requiring invasive intervention. 
2. IPSS score of ≥ 15. 
3. Qmax: Peak flow rate ≤ 15 ml/sec. 
4. Post-void residual (PVR) < 300 ml. 
5. Prostate transverse diameter > 30 mm. 
6. Prostate volume between 20 to 120 gm. 
7. Voided volume ≥ 125 ml.  
8. Subject able to complete the study protocol in the opinion of the Principal 
Investigator. 
9. Subject must be willing to undergo the procedure without anesthesia.  
5.5 
EXCLUSION CRITERIA  
1. History of any illness or surgery that in the opinion of the Principal Investigator 
may confound the results of the study. 
2. Presence of a penile implant. 
3. Any prior minimally invasive intervention (e.g. TUNA,Laser, Microwave) or 
surgical intervention for the symptoms of BPH. 
4. Currently enrolled in another clinical trial. 
5. Confirmed or suspected malignancy of prostate or bladder. 
6. Previous rectal surgery (other than hemorrhoidectomy) or history of rectal 
disease. 
7. Previous pelvic irradiation or radical pelvic surgery. 
8. Documented active urinary tract infection by culture or bacterial prostatitis 
within last year documented by culture (UTI is defined as >100,000 colonies per 
ml urine from midstream clean catch or catheterization specimen). 
9. Neurogenic bladder or sphincter abnormalities. 
10. Urethral strictures, bladder neck contracture or muscle spasms. 
11. Bleeding disorder (note that use of anti-platelet medication is not an exclusion 
criterion). 
12. Subjects who are interested in maintaining fertility. 
13. Use of concomitant (or recent) medications to include the following: 
a. Beta blockers, antihistamines, anticonvulsants, and antispasmodics within 
1 week of treatment, unless there is documented evidence of stable dosing 
for last 6 months (e.g., no dose changes). 
b. Alpha blockers, antidepressants, anticholinergics, androgens, or 
gonadotropin-releasing hormonal analogs within 2 weeks of treatment. 
c. 5-alpha reductase inhibitor within the last 6 months 
14. Subject is unable or unwilling to go through a “washout” period for the above 
medications prior to treatment. 

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15. Subject has chronic urinary retention. 
16. Significant urge incontinence. 
17. Poor detrusor muscle function. 
18. Neurological disorders which might affect bladder or sphincter function. 
19. Bladder stones. 
20. Renal impairment. 
21. In the opinion of the Principal Investigator, subject will not be able to adequately 
tolerate a rigid cystoscopy-type procedure. 
22. Unable or unwilling to sign the Informed Consent Form (ICF) and/or comply 
with all the required follow-up requirements. 
23. Any cognitive disorder that interferes with or precludes a subject from directly 
and accurately communicating with the Principal Investigator regarding the 
study. 
24. Peripheral arterial disease with intermittent claudication or Leriches Syndrome 
(i.e., claudication of the buttocks or perineum). 
25. Biopsy of the prostate within 30 days prior to the Rezūm procedure. 
6 STUDY PROCEDURES 
6.1 
SUBJECT ENROLLMENT 
Only subjects who meet the inclusion/exclusion criteria will be eligible to participate in the 
study.  It is recommended that only subjects that live within 90 minutes of driving distance 
from the study site be selected as participants in the study due to the study follow-up 
requirements. 
 
Once it is determined that a subject meets the enrollment criteria (except for the use of the 
concomitant medication), the subject will be given an informed consent to read.  Subjects 
that were on BPH medication will then go through a washout period.  If the subject 
successfully goes through the washout period and still meets the selection criteria, the subject 
will be considered enrolled and assigned an enrollment ID.  
 
The Principal Investigator (PI) or study coordinator will review the informed consent with 
the subject to be sure the subject completely understands the meaning of the consent.  Upon 
completion, the subject will be given an opportunity to sign the informed consent.  A subject 
will be considered officially enrolled only if treatment with the NxThera Rezūm System is 
attempted. 
6.2 
SCREENING AND BASELINE EVALUATIONS 
The following evaluations will be completed for all study candidates who have provided a 
written informed consent: 
 
 Complete general medical and genitourinary history (including any 
previous treatment for LUTS; if pharmacologic, name of drug(s) as well 
as dosage) and duration of subject’s BPH symptoms. 
 Blood analysis: 
o Complete blood cell count (CBC) 
o Blood urea nitrogen  (BUN) 

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o Serum creatinine 
o Serum prostate-specific antigen (PSA) level 
o Electrolytes 
 Uroflowmetry: 
o Voided volume (must be ≥ 125 mL or test must be repeated)  
o Total time of voiding 
o Peak flow rate (Qmax; also known as PFR)  
o Average urinary flow rate 
o Post-void residual urine volume (PVR; may be measured by 
either ultrasound or catheterization but the same method must be 
used pre- and post-treatment) 
 Urinalysis 
o Urine culture, if indicated 
o Subject questionnaires: 
o International Prostate Symptom Score (IPSS)  
o BPH Impact Index (BPHII) 
o International Index of Erectile Function (IIEF) 
o Male Sexual Health Questionnaire Short Form (MSHQ-EjD 
Short Form) 
o Prostate volume (PV), length and width, as measured by TRUS 
o Confirmation of function of detrusor muscles via urodynamics 
 Subjects must undergo a “washout” period of 6 months if they have been 
on: 
o 5-alpha reductase inhibitor 
o Subject must undergo a “washout” period of 2 weeks if they have 
been on: 
o alpha blockers  
o antidepressants 
o anticholinergics 
o androgens 
o gonadotropin-releasing hormonal analogs  
o Subject must undergo a “washout” period of 1 week if they have 
been on: 
o Beta-blockers  
o Antihistamines 
o Anticonvulsants 
o Antispasmodics 
o Unless subjects have been on a stable dosing for the last 6 months 
(i.e. no changes) 
6.3 
CONCOMITANT THERAPY 
Therapy (medication and non-medication therapies) not restricted by a protocol 
requirement may be used during the study for the treatment or prevention of disease or to 
maintain good health.  However, subjects should not take concomitant medications that 
affect the BPH symptoms which might confound the study result, per the PI’s discretion.  
6.4 
SUMMARY OF PRE-PROCEDURE PREPARATION 

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All eligible subjects who have signed an informed consent and are on alpha blockers or beta 
blockers will undergo a washout period of 2 weeks or 7 days, respectively.  Subjects who have 
been on a stable dosing of beta blockers for the last 6 months (i.e. no dose changes) do not 
need to undergo the 7 day washout period. 
 
Subjects are to be given an oral anti-anxiety medication prior to treatment.  This medication 
must be given at least 45 minutes prior to the procedure, but no more than 2 hours before the 
procedure.  No anesthesia will be allowed.  Pain killer may be prescribed at the physician’s 
discretion.   
6.5 
FOLLOW-UP 
The following evaluations will be completed at the follow-ups as indicated: 
Table 6-1:  Evaluations at Follow Up 
Follow up period 
Description 
1 day  
(1-2 days) 
Check for AE 
IPSS 
Pain assessment 
Medications 
1 week  
(4-7 days) 
Check for AE 
Pain assessment 
IPSS, Subject Satisfaction Questionnaire 
Cystoscopy 
Uroflow 
MRI 
Medications 
1 month 
(3-5 weeks) 
 
Check for AE 
Pain assessment 
Uroflow 
IPSS, BPHII, IIEF, EQ5D, MSHQ-EjD SF 
MRI  
Medications 
3 months 
(12 – 14 weeks) 
Check for AE 
Pain assessment 
Uroflow 
IPSS, BPHII, IIEF, EQ5D, MSHQ-EjD SF, Subject 
Satisfaction Questionnaire 
PSA 
Prostate Volume  
MRI 
Medications 
6 months 
(24-28 weeks) 
Check for AE 
Pain assessment 
Uroflow 
IPSS, BPHII, IIEF, EQ5D, MSHQ-EjD SF, Subject 
Satisfaction Questionnaire 
PSA 

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Prostate Volume 
MRI  
Medications 
12 months  
(11-13 months) 
Check for AE 
Pain assessment 
Uroflow 
IPSS, BPHII, IIEF, EQ5D, MSHQ-EjD SF, Subject 
Satisfaction Questionnaire 
PSA 
Prostate Volume 
Medications 
Annually for up to 5 
years.  Annual check 
up may be within 2 
months of the 
anniversary of the 
procedure 
 
Check for AE 
IPSS, BPHII, EQ5D, MSHQ-EjD SF, Subject Satisfaction 
Questionnaire 
Medications 
Unscheduled 
Check for AE 
Pain assessment (optional) 
Medications 
IPSS, BPHII, IIEF,MSHQ-EjD SF (all optional) 
Uroflow (optional) 
 
 

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6.5.1 Scheduled Follow-up Visits 
Table 6-2: Schedule of Visits  
 
Baseli
ne 
Pre-
Op 
1 
day 
1 
week 
1 
month 
3 
month
s 
6 
month
s 
 
1 year 
 
Annual 
(2-5 
years) 
Unsched
uled 
IPSS 
 
 
 
 
 
 
 
 
optional 
BPH Impact 
Index 
 
 
 
 
 
 
 
 
optional 
EQ5D 
 
 
 
 
 
 
 
 
 
Sexual 
function (IIEF) 
 
 
 
 
 
 
 
 
optional 
MSHQ-EjD 
Short Form 
 
 
 
 
 
 
 
 
optional 
Subject 
Satisfaction 
Questionnaire 
 
 
 
 
 
 
 
  
optional 
Subject Pain 
Assessment 
 
 
 
 
 
 
 
 
 
Uroflow 
(Qmax + PVR) 
 
 
 
 
 
 
 
 
optional 
Urodynamics 
 
 
 
 
 
 
 
 
 
Prostate 
specific antigen 
(PSA) 
 
 
 
 
 
 
 
 
 
Prostate 
Volume 
 
 
 
 
 
 
 
 
 
Cystoscopy 
 
 
 
 
 
 
 
 
 
MRI 
option
al 
 
 
 
 
 
 
 
 
Adverse 
event(s)  
 
 
 
 
 
 
 
 
 
Medication(s) 
used  
 
 
 
 
 
 
 
 
 
 
 
 

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7 ADVERSE EVENTS 
7.1 
DEFINITION OF ADVERSE EVENT(S) 
For the purpose of this protocol, an “adverse event” (AE) will be defined as any adverse 
medical condition change (i.e., de novo or increased severity in a preexisting condition) from 
the subject’s baseline condition that occurs during the course of the clinical study, after 
starting study procedure, whether considered procedure-related or not.  Therefore, 
conditions existing at the time of enrollment will not be reported as an AE unless the event 
increased in clinically significant severity during the course of the study.  Events which 
resolve and then recur should be reported as separate AEs.  Events that are a continuation of 
an unresolved AE should not be reported as a new AE but a continuation of the previously 
reported AE. 
 
The reason for catheterization will not be considered an AE if catheterization occurs and 
ends within 72 hours after the procedure because this is generally considered standard of 
care to allow the tissue to heal.   
 
The reason for catheterization will be considered an adverse event if the following applies: 
a. If catheterization occurs within a 72-hour window after the procedure and the 
duration of catheterization extends beyond that 72-hour window 
b. If catheterization occurs outside of a 72-hour window after the procedure 
c. If catheterization recurs after the same symptom is resolved 
 
Lower Urinary Tract Symptoms (LUTS) will not be considered an adverse event if LUTS 
occurs and ends within a 3-day window (72 hours)  after the procedure. 
 
Lower Urinary Tract Symptoms (LUTS) will be considered an adverse event if the following 
applies: 
a. If LUTS occurs within a 3-day window (72 hours) after the procedure and the 
duration of LUTS extends beyond that 3-day window (72 hours) 
b. If LUTS occurs outside of a 3-day window (72 hours) after the procedure 
c. If LUTS recurs after the same symptom is resolved 
 
Normally expected symptoms caused by the treatment will not be considered AEs for this 
study.  For example, normal pain or minor bruising at the surgical site due to the healing of 
the site will not be considered an AE.  “Treatment” includes all procedures and treatments 
administered according this protocol. 
 
An AE may be volunteered spontaneously by the subject or discovered as a result of 
questioning or by physical examination by the investigator.   
 
AEs should be classified according to their underlying cause, if known, (e.g., fever resulting 
from infection should be reported as “infection”).  Concomitant AEs that are unrelated (in 
the clinician’s judgment) should be reported as separate events. 
 
AE determination is based on three levels of evidence: 
Level 1 – final diagnosis 

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Level 2 – signs 
Level 3 – symptoms 
 
Every effort should be made to collect Level 1 evidence of any AE.  If an AE has all three 
levels of evidence, an AE should be reported only once at the highest level of severity, which 
is the final diagnosis (Level 1).  A single AE should not be reported as multiple AEs based on 
separate symptoms, signs, and diagnosis. 
 
In cases where a diagnosis is not possible, AE determination should be based on the next 
highest level of evidence (signs, Level 2), followed by symptoms (Level 3), if only symptoms 
are available.  
 
A corrective action itself is not an AE.  The AE should always be determined based on the 
reason that a corrective action was taken.   
 
Note: there may be multiple symptoms representing or associated with only one AE.  In this 
case only one AE should be reported.  The symptoms can be captured within the AE 
description.  If the symptoms are related to LUTS, complete the LUTS form in addition to 
the AE form.  If AE requires catheterization, then complete the catheterization form. 
 
Figure 7-1 is an AE determination and outcome flowchart. 
  
Complaint
Or Symptoms of 
AE?
Was 
there a medical
 exam?
Was 
there a final 
diagnosis?
Record Sign 
as AE
(Level 2)
Record 
diagnosis as AE
(Level 1)
Record AE as 
symptom
(Level 3)
Yes
Yes
No
No
Did AE 
cause death, 
permanent injury, 
Hospitalization or
required invasive 
intervention?
Report as SAE
Report as 
AE
Yes
No
 
 
Figure 7-1: AE Determination and Outcome Flowchart 
 
 

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Examples 
Subject is diagnosed with urinary retention and requires catheterization for more than 3 
days.  In addition, they have symptoms of irritation, urgency, and hematuria.  Only one AE – 
retention should be reported.  The additional symptoms should be noted in the AE 
description.  Catheterization is the treatment. 
7.2 
STUDY RELATED AE DEFINITION 
This section applies particularly to the Phase 2 part of the study.  The transurethral 
intervention with a rigid scope similar in size to the Rezūm device commonly is associated 
with transient symptoms.  For the purpose of this study, these types of transient symptoms 
will not be considered an adverse event.  The corollary to a surgical procedure is bleeding.  
Bleeding will occur in all surgical BPH procedures, and bleeding, therefore, is not clinically 
significant and typically not reported as an AE.  The following types of signs and symptoms 
that are attributed to the procedure, last less than or equal to 72 hours, AND do not result in 
intervention, re-hospitalization, or prolonged unplanned hospitalization, will not be 
considered AEs. 
 
 Dysuria 
 Hematuria 
 Storage (irritative) LUTS 
 Urgency/frequency 
 Nocturia 
 Urge incontinence 
 Voiding (obstructive) LUTS 
 Hesitancy 
 Decrease flow 
 Increase residual 
 Pain/discomfort 
 Catheterization 
7.2.1 Erectile Dysfunction and Retrograde Ejaculation 
Erectile dysfunction (ED) is commonly present in this population group.  Therefore, only de 
novo ED and retrograde ejaculation attributable to the procedure within the first 3 months 
will be considered an AE.  ED is a progressive disease and is expected to increase in 
frequency with age regardless of the procedure. 
7.3 
ANTICIPATED ADVERSE EVENT(S) 
Anticipated adverse device events are those that may be reasonably expected to occur in 
association with a surgical BPH procedure, and include those listed here or reported in the 
literature associated with a minimally invasive BPH ablation procedure: 
 Pain 
 Bleeding 
 Infection / fever 

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 Perforation 
 Retrograde ejaculation 
 Urinary symptoms including: 
 Dysuria 
 Frequency 
 Urgency 
 Nocturia 
 Urinary retention 
 Temporary acute incontinence 
 Sensation of not emptying bladder completely 
 Transient incontinence 
 Urethral stricture 
 Urethritis 
 Irritative urinary symptom 
 Urethral injury 
 Urinary clot retention 
 Chronic pain at site 
 Bladder spasm 
 Rectal, perianal findings 
 Anal irritation 
 Flu-like symptoms 
 Hematospermia 
 Epididymitis 
 Blood pressure change during therapy 
 Flank pain 
 Blood loss (> 50 ml)  
 Bowel irritation 
 Erectile dysfunction 
 Retrograde ejaculation 
 Pressure sensation 
 Prostatitis 
7.4 
SERIOUS ADVERSE EVENT(S) 
An AE is considered to be serious if it: 
 Results in death (as part of any surgical procedure there is a chance of this SAE); 
 Is life threatening; 
 Requires subject hospitalization or prolongation of existing hospitalization; 
 Results in persistent or significant disability/incapacity; 
 Is considered an important medical event 
  
Important medical events that may not meet one of the above definitions could be considered 
SAEs if they jeopardize the health of the subject, or require surgical intervention to prevent 
one of the outcomes listed in the above definition.  Serious adverse events may or may not be 
related to the Rezūm procedure. 

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7.5 
UNANTICIPATED ADVERSE DEVICE EFFECT(S) (UADE) 
An unanticipated adverse device effect is any serious adverse effect on health or safety or 
any life threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in 
the ”investigational plan” or application (including a supplementary plan or application), or 
any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
7.6 
REPORTING OF ALL ADVERSE EVENTS 
All AEs that occur to any subject during the study must be documented on the Adverse 
Event CRF, including the following information: event description, treatments given, 
intensity of the event, relationship with the device, and the outcome of the event.   
 
If the Principal Investigator determines that an AE is a SAE or a UADE, all as defined in 
this protocol, it is to be reported to the Sponsor as soon as possible but no later than 10 
working days after the Principal Investigator first learns of the incident.  The Sponsor will 
investigate any reported SAE or UADE to determine if the event type and severity was 
anticipated in the investigational plan.   
 
Investigators are required to report all UADEs to the reviewing ethics committee (EC) no 
later than 10 working days from the date that the Principal Investigator first became aware 
of such UADE.  In addition, the Principal Investigator must comply with any other reporting 
requirements of the reviewing EC. 
 
A Sponsor who conducts an evaluation of a UADE shall report to all reviewing EC’s and 
participating Investigators within 10 working days after the Sponsor first receives notice of 
the effect. 
 
The Sponsor also must take the appropriate action regarding termination of the study when 
it is determined that an AE presents an unreasonable risk to subjects.  Any such termination 
must occur no later than 15 working days from receipt of notice of the adverse event. 
7.7 
RELATIONSHIP OF AES TO THE STUDY DEVICE 
How any AE related to the study procedure will be reported on the Adverse Event CRF and 
be determined by the Principal Investigator using the following definitions: 
Definite:  The AE follows a reasonable temporal sequence from the time of index 
procedure.  This includes an AE that occurs during the index procedure and during 
the follow-up period. 
Probable:  The AE follows a reasonable temporal sequence from the time of index 
procedure and the possibilities of factors other than the index procedure, such as 
underlying disease, concomitant drugs, or concurrent treatment can be excluded. 
Possible:  The AE follows a reasonable temporal sequence from the time of index 
procedure and the possibility of index procedure involvement cannot be excluded.  
However, other factors such as underlying disease, concomitant medications, or 
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Unlikely:  The AE has an improbable temporal sequence from the time of index 
procedure, or it can be reasonably explained by other factors, including underlying 
disease, concomitant medication, or concurrent treatment. 
Not related: The AE has no temporal sequence from the time of the index procedure, 
or it can be explained by other factors, including underlying disease, concomitant 
medication, or concurrent treatment. 
7.8 
DEGREE OF SEVERITY 
The degree of severity of the AE to the subject’s health will be determined by investigator 
and documented on an Adverse Event CRF: 
Minimal: Awareness of the event but easily tolerated 
Moderate: Discomfort enough to cause interference with usual activity 
Severe: Inability to carry out usual activity 
 
8 TRAINING 
The training of appropriate clinical site personnel will be the responsibility of NxThera, as 
the study Sponsor.  All physicians proctored by NxThera or another trained physician must 
sign the site Proctoring Form.  To ensure proper surgical technique, uniform data collection 
and protocol compliance, NxThera will present a formal training session to study site 
personnel.  At this training session, the study protocol, techniques for the identification of 
eligible subjects, instructions on data collection, schedules for follow-up and regulatory 
requirements will be reviewed. 
9 DEVICE MALFUNCTIONS 
All failures and malfunctions of the study device must be documented on the Device 
malfunction/Performance CRF and faxed to the Sponsor, preferably within 24 hours of 
knowledge of the event.  In the event of a device malfunction every effort must be made to 
return the suspected device to the Sponsor for analysis.  All device performance issues and 
malfunctions will be reported in the clinical results (e.g. final report). 
10 STUDY MANAGEMENT 
This study is being conducted following “good clinical practices” (GCP).  The Sponsor or a 
Sponsor representative will monitor the progress of the study as required by GCP and as 
specified by the study monitoring plan.  This monitoring will include routine, periodic visits 
to study sites to compare reported results with source documentation. 
10.1 SUBJECT IDENTIFICATION 
Subjects participating in the study will be assigned a unique identification code (ID) using 
the format “XXX-YYY” where: 
 
XXX = Institution Number, assigned by the Sponsor to each study site 
YYY = Enrollment Number, assigned by the institution as each subject is enrolled in the 
study. 
 

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In addition to the ID, each subject’s initials will be used as an identifier included on 
documentation submitted to the Sponsor. 
 
For Phase 1 Acute subjects, an “A” will be added as a Prefix to the subject ID. 
For Phase II Optimization subjects, an “O” will be added as a Prefix to the subject ID. 
10.2 CENTRAL DATABASE 
All study documentation will be collected and compiled in a central database by the Sponsor.  
Appropriate quality control measures will be established to ensure accurate and complete 
transfer of information from the study documentation to the central database. 
11 REGULATORY RESPONSIBILITIES 
11.1 ETHICS COMMITTEE (EC) APPROVAL 
The Principal Investigator must submit the study protocol to their EC and obtain the EC’s 
written approval before being allowed to conduct and participate in the study.  The Principal 
Investigator also is responsible for fulfilling any conditions of approval imposed by the EC, 
such as regular reporting, study timing, etc.  The Principal Investigator will provide Sponsor 
or its designee with copies of such approvals and reports. 
11.2 INFORMED CONSENT FORM (ICF) 
The Sponsor will provide a template ICF to each site for EC submission.  This template may 
be modified to suit the requirements of the individual study site.  The Sponsor must pre-
approve all changes to the ICF prior to initial submission to the EC.   
 
The Principal Investigator or assigned designee must administer the EC -approved version 
of the ICF to each prospective study subject, and obtain the subject’s signature or a legally 
approved designee’s signature along with the date of consent prior to enrollment in the study.  
Subjects must be informed about their right to withdraw from the study at any time and for 
any reason without sanction, penalty, or loss of benefits to which the subject is otherwise 
entitled and also informed that withdrawal from the study will not jeopardize their future 
medical care.  A copy of the signed ICF must be given to each subject enrolled in the study. 
11.3 CONFIDENTIALITY 
All information and data sent to the Sponsor concerning subjects or their participation in this study 
will be considered confidential.  Data used in the analysis and reporting of this evaluation will be 
used in a manner without identifiable reference to the subject.   The Principal Investigator consents 
to the visits by the staff of the Sponsor and its authorized representatives and the U.S. FDA or any 
other local governmental body to review the study subjects’ medical records, including any test or 
laboratory data that might have been recorded on diagnostic test media (e.g., cystograms).   
11.4 AMENDING THE PROTOCOL 
Neither the Principal Investigator nor the Sponsor will modify the Investigational Protocol 
without first obtaining concurrence of the other in writing.  All changes must be submitted to 
the EC for review and approval.  Any change that would require alteration of the ICF must 
receive approval from the EC prior to implementation.  Following approval, the protocol 
amendment will be distributed to all protocol recipients at the site. 

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11.5 PROTOCOL DEVIATIONS 
A Protocol Deviation CRF must be completed for each study protocol deviation (e.g., failure 
to obtain informed consent, enrolling a subject who does not meet inclusion / exclusion 
criteria, not performing required testing, missed follow-up window, etc.).  An investigator 
must notify the Sponsor and the reviewing EC of any deviation from the Study Protocol that 
was done to protect the life or physical well-being of a subject.  Such notice should be given 
as soon as possible, but no later than five working days after the emergency occurred. 
11.6 SITE NONCOMPLIANCE 
Repeat serious protocol deviations will be closely monitored.  If excessive deviations or a 
failure to reduce deviations are noted, the Sponsor reserves the right to suspend study 
enrollment at that site until a sufficient system is in place at the site to reduce further 
deviations (21 CFR §812.46(a)). 
11.7 DEVICE ACCOUNTABILITY 
A Device Tracking Log (DTL) will be maintained at each investigational site and will be 
provided by the Sponsor. The BPH Rezūm Systems and Delivery Devices allocated for 
investigational site use will be recorded in the log upon delivery to the investigational site and 
will be stored in a secured area until use.  Each site will be responsible for tracking the 
receipt and disposition of all investigational BPH Rezūm Systems and Delivery Devices.  All 
unused BPH Rezūm Systems and Delivery Devices at the end of the study must be returned 
to the Sponsor.   
 
The DTL will be updated as each BPH Rezūm System is delivered, used, or returned.  The 
DTL will contain delivery dates, used dates, returned-to-sponsor dates, serial numbers, 
expiration dates and model and/or unit numbers of the BPH Rezūm Systems and/or Delivery 
Devices delivered to the site, and the subject IDs associated with all BPH Rezūm Systems and 
/or Delivery Devices that are used. 
11.8 SPONSOR RESPONSIBILITIES  
NxThera, Inc. is the Sponsor of this study.  NxThera’s responsibilities in the study include: 
Provide training to Principal Investigator, other physicians, and the staff of the study 
site. 
Select the Principal Investigator, all clinical investigators and study sites, and other 
consultants (e.g., monitors) who participate in the study. 
Provide financial support to each study site. 
Ensure completion of site monitoring of clinical data at clinical study sites.  
Retain ownership of all clinical data generated in this study, and control the use of the 
data for appropriate purposes only.   
11.9 PRINCIPAL INVESTIGATOR RESPONSIBILITIES  
The Principal Investigator is responsible for ensuring the investigation is conducted 
according to all signed agreements, the study protocol and applicable laws and regulations.  
Also, the Principal Investigator may not begin enrollment until Sponsor or its designee 
receives and approves (when necessary) the following documents: 
 
Signed Investigator Agreement 

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 
Financial Disclosure Forms for all participating investigators 
 
EC Roster 
 
EC Protocol and ICF Approvals 
 
Investigators’ current curricula vitae (CV) 
 
Signed Site Delegation Log 
11.10 CASE REPORT FORMS (CRFS) 
CRFs are used to record study data and are an integral part of the study and 
subsequent reports.  Therefore, the data must be legible and complete.   
 
CRFs will be provided by the sponsor representative via eDC. 
All subject questionnaires will be provided by the sponsor representative as paper 
CRFs. 
 
MRI Core Lab Forms will be provided by the sponsor representative as paper CRFs. 
These will then be sent to Libra Medical for data entry into the database. 
 
All paper CRFs must be completed using a pen.  Corrections of data on the CRF should be 
made by crossing out, but not obliterating, the incorrect data with a single line; writing the 
correct value next to that crossed out; and, at each change, initialing and dating by the 
person making the change.  Correction fluids and covering labels must not be used.  If the 
original CRFs have already been submitted to the data management, the Sponsor will initiate 
a Data Clarification Form to be completed by study site personnel.   
eCRFs must be signed by the study investigator. 
Queries will be created in the database if there are missing data or if there is a question 
about the data submitted following a data review. The site representative will answer the 
query or correct the data accordingly. The query must be approved by a monitor, data 
manager or project manager. 
12 MONITORING PROCEDURES 
The site will be monitored to ensure compliance during the study.  Monitoring will consist of 
review of subject records, source documents, and other required documentation, including 
EC approvals and correspondence.  The site staff must be available to meet with the monitor 
or other study Sponsor representative during site visits. 
 
The monitoring will be performed in accordance with study Monitoring Plan. The 
monitoring will be done by the Sponsor representative: 
 
Libra Medical, Inc.  
8401 73rd Ave N, Suite 63 
Minneapolis, MN 55428 
Tel: 763-477-5606 
Fax: 763-477-6357 
Email: bschnabel@libramed.com 
13 REPORTS AND RECORDS 

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13.1 REPORTS 
Table 13-1 displays a list of the reports that are the responsibility of the Principal 
Investigator to report to the Sponsor.  Each study investigator must follow their site’s 
reviewing EC reporting requirements.  If applicable regulations or EC requirements 
mandate stricter reporting requirements than those listed, the stricter requirements must be 
followed. 
 
Table 13-1:  Reports Required from Investigators to Sponsor 
Type of Report 
Time Constraints of Notification (from the time study site personnel 
learned about the event) 
Subject death  
Written reports (e.g., via e-mail) within 48 hours 
SAE or UADE 
Within 10 working days 
Report of subject enrollment 
Daily 
Subject withdrawal 
Within 5 working days (e.g., by fax, e-mail) 
Withdrawal of EC approval 
Immediately by telephone/e-mail followed by a copy of the notification 
within 5 working days 
Significant deviations from Study Protocol 
Within 5 working days 
Informed consent not obtained 
Within 5 working days 
13.2 RECORDS 
The Principal Investigator must maintain the following accurate, complete, and current 
records relating to the conduct of the investigation.  The final responsibility for maintaining 
such records remains with the Principal Investigator.  These include: 
 All correspondence with another investigator, an EC, a laboratory, Sponsor or 
its designee (e.g., monitor); 
 Records of each subject’s case history, including study-required CRFs, signed 
ICF, all relevant observations of AEs, the condition of each subject upon 
entering and during the course of the investigation, relevant medical history, 
the results of all diagnostic testing, etc.; 
 Study personnel visit log;  
 Any other records that applicable regulation requires to be maintained 
14 OTHER STUDY ELEMENTS 
14.1 INVESTIGATORS AND PATIENT POPULATION 
The Principle Investigator (PI) for this study is Dr. Edwin Rijo from the Canela Clinic in La 
Romana, Dominican Republic. 
 
Subjects for this study will be recruited from the PI’s practice, will have been diagnosed with 
BPH and scheduled for surgery (Phase 1 Acute) or would otherwise be treated surgically or 
with other minimally invasive BPH treatment (Phase 2 – Optimization). 
14.2 STATISTICAL ANALYSIS 
Descriptive statistics will be calculated and reported for study variables, as appropriate.  
Continuous variables (e.g., symptom score, uroflowmetry, quality of life assessments) will be 
summarized using statistics such as means, standard deviations and absolute change from 
baseline.  Categorical variables (e.g., adverse events) will be summarized as frequency 

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distributions.  Adverse events and technical observations will be reported by frequency of 
occurrence, severity and relationship to the vapor treatment device. 
 
All subjects enrolled in this study (including those withdrawn from the study or lost to 
follow-up) will be accounted for and documented.  
14.3 UNSCHEDULED FOLLOW-UP VISITS 
If subjects are seen for unscheduled/interim visits because of an AE, appropriate Clinical 
Report Form(s) (CRF(s)), including the AE CRF, will be completed, if applicable. 
14.4 LOST TO FOLLOW-UP 
If a subject fails to comply with follow-up evaluations, the investigational site must make 
repeated attempts (at least three) to contact the subject.  Each attempt to contact the subject 
and the method used (e.g., telephone contact, registered letter) must be documented in the 
subject’s records.  A last unsuccessful attempt to contact a subject must be documented by a 
returned, registered letter sent to the subject.  
 
If a subject misses one of the follow-up evaluations but is present at the subsequent follow-
up, the subject can be readmitted into the study and queried retrospectively for basic 
information; however, the missed evaluation must be documented on a Protocol Deviation 
CRF. 
14.5 SUBJECT WITHDRAWAL FROM STUDY 
14.5.1 Voluntary Withdrawal 
A subject may voluntarily withdraw from the study at any time.  If a subject officially 
withdraws from the study, the investigator must ensure that there is documentation for the 
reason for the withdrawal.  If the subject had an AE, the subject should be followed until the 
resolution of the AE, if possible. 
14.5.2 Withdrawal Due to Exclusion Criteria 
A subject may be withdrawn from the study if subject is later found to not meet study 
selection criteria.  
14.5.3 Involuntary Withdrawal 
A subject may also be withdrawn from the study at the discretion of the investigator (e.g., for 
non-compliance with medical advice). 
14.6 END OF STUDY 
Subjects may be exited from the study at the end of the study (i.e., study discontinuation by 
the Sponsor) or when the subject has completed the 5 year follow-up visit.  An End of Study 
CRF will be completed at the time of study completion or discontinuation. 
14.7 DESCRIPTION OF TESTS AND EVALUATIONS 
14.8 SUBJECT QUESTIONNAIRES 

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All questionnaires are self-administered and will be completed at baseline and at each 
follow-up visit.  Questionnaires completed at baseline will be compared to those completed at 
each follow-up visit to assess any effect of treatment.  The following assessments will be 
administered. 
14.8.1 IPSS1  
The IPSS is a standardized, validated, and reliable self-administered questionnaire that 
utilizes 7 questions to assess the frequency and severity of a subject's obstructive and 
irritative symptoms, with each question scored on a scale of 0 (not at all) to 5 (almost always).  
Total scores on the IPSS can range from 0-35; a score of 7 or less represents subjects with 
mild symptoms; 8-19 represents those with moderate symptoms; and subjects with scores 
from 20-35 typically have severe symptoms. 
14.8.2 IIEF2 
The IIEF is a validated self-administered questionnaire designed for detecting treatment-
related responses in patients with erectile dysfunction.  In addition, the IIEF provides a 
broad measure of sexual function. 
14.8.3 MSHQ-EjD Short Form3 
The MSHQ-EjD Short Form is a self-administered questionnaire designed to assess 
ejaculatory dysfunction. The questionnaire consists of three ejaculatory function 
questions and one ejaculation bother question.  
14.8.4 BPH Impact Index4 
The BPH Impact Index is a self-administered questionnaire that measures the impact of 
BPH symptoms on the subjects’ quality of life.  The questionnaire assesses the extent to 
which the symptoms cause physical discomfort, anxiety/worry, bothersomeness, or otherwise 
affect activities of daily living. 
14.8.5 EQ5D™5 
EQ-5D is a standardized instrument used to measure health outcomes.  The EQ-5D is a self-
reported generic preference-based measure of health, developed by the EuroQol Group.  The 
instrument can be applied to, and has been shown to be valid for, a wide range of health 
conditions.  The EQ-5D has been used in many studies as a way of capturing the health-
related quality of life of patients, trial participants and the general public. 
14.8.6 Subject Satisfaction Questionnaire 
This questionnaire is specific to the NxThera Rezūm System treatment and will measure 
overall satisfaction with the procedure, recommendation of treatment to friends/family and if 
the subject would undergo the treatment again if symptoms were to recur after 5 years. 
14.8.7 Magnetic Resonance Imaging (MRI) with Gadolinium:  
MRI T2 imaging, with dynamic gadolinium enhancement, will be performed on all subjects 
one week following the study treatment.  Size and location of gadolinium defects will be 
independently assessed using Analyze® imaging software, a multi-dimensional, biomedical 
image display and analysis application.   

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14.8.8 Necropsy and TTC Stain 
For Phase 1 of this study, gross necropsy will begin by placing the treated prostate specimen 
on a board for closer visual and tactile observation, measurements and pictures.  Digital 
pictures will be taken of the treated prostate, and the prostate then will be sliced serially and 
the slices exposed for visual observation and digital documentation.  Each of these tissue 
slices then will be submerged into tetrazolium hydrochloride to enhance the visual distinction 
between treated and untreated tissue.  Treatment volume will be estimated from these slices.  
Observation and measurements will be recorded on the data sheets for each specimen.  The 
sliced, stained tissues will be placed in formalin for the pathology histology examination. 
14.8.9 Post Void Residual (PVR) 
PVR will be determined using abdominal ultrasound, bladder scanner, or in/out 
catheterization.  Prior to the enrollment of any subject, the study machine at each site will be 
identified and its accuracy verified.  
14.8.10 Uroflow  
The uroflow meter parameters will be measured using the uroflow meter.  The print-out of 
the uroflowmeter must be sent to Libra Medical for adjudication. 
14.8.11 Prostate Size: 
For Phase 1, the extirpated prostate tissue mass/volume will be determined by submerging 
the treated prostate in isotonic saline in a graduated cylinder or a weight scale.   
14.8.12 Transrectal ultrasound (TRUS) 
For Phase 2; a TRUS will be performed on each subject during screening prior to treatment 
in order to obtain the subject’s prostate dimensions and assist the PI in the development of 
each subject’s treatment plan.  TRUS also will be used to monitor the subject’s prostate size 
at the follow up. 
14.8.13 Urinary Tract Infection (UTI) Assessment:  
UTI assessment data will be collected per normal laboratory standards.  Investigators may 
conduct a urinalysis using a standard dipstick or may send a urine sample to the laboratory 
for culture.   
 
14.8.14 Wong Baker Pain Scale  
The Wong Baker scale is a validated measurement instrument intended to measure the 
amount of pain that a patient feels which ranges across a continuum from none to an extreme 
amount of pain.  The pain scale is shown in pictorial form instead of a line.  Each subject 
selects the response that he feels best represents his perception of his then current pain level.   
14.9 SUSPENSION OR EARLY TERMINATION OF THE CLINICAL INVESTIGATION 
If the clinical study is terminated prematurely or suspended, NxThera, as Sponsor, will 
promptly inform the Principal Investigator of such termination or suspension, and the 
reason(s) for this decision.  The EC also shall be informed promptly and provided with the 
reason(s) for the termination or suspension by the Sponsor or by the Principal Investigator. 

CONFIDENTAL: Contains Proprietary Information 
 
 
 
CONFIDENTIAL   
1633-001 Rev03 Rezum FIM 
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15 REFERENCES 
                                                 
 
 
1 Barry MJ, Fowler FJ Jr, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK. 
Measuring disease-specific health status in men with benign prostatic hyperplasia. 
Measurement Committee of The American Urological Association. Med Care. 1995 Apr;33(4 
Suppl):AS145-55. 
2 Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, and Mishra A. (1997) The international index of 
erectile function (IIEF): A multimentional scale for assessment of erectile dysfunction. Urology 49(6) 822-830 
3 Rosen, R.C. et al. Development and Validation of Four-Item Version of Male Sexual Health Questionnaire to 
Assess Ejaculatory Dysfunction. Urology. 2007 May; 69 (5): 805-809. 
4 Copyright © 2003 American Urological Association Education and Research, Inc. 
5 EQ-5D™ is a trade mark of the EuroQol Group