The Use of Gabapentin for Post-Operative Pain Control and Narcotic Reduction in Scrotal Surgery
Phase: PHASE3
Conditions: Non-obstructive Azoospermia
Sponsor: Weill Medical College of Cornell University

 
 
  
Page # i 
 
TITLE:  The Use of Gabapentin for Post-Operative Pain Control and Narcotic Reduction in Scrotal Surgery  
 
IRB Protocol #:  19-08020686 
 
NCT #: NCT04230980 
Version Date: April 20, 2023  
Funding Source(s): Internally funded 
 
Principal Investigator:  
 
Jonathan Gal, MD 
525 East 68th Street, A 900 
212-746-5470 
212-746-0977 
jog4018@med.cornell.edu 
 
 
Co-Investigators: 
 
Peter N. Schlegel 
525 East 68th Street, Starr 900 
212-746-5491 
212-746-8425 
pnschleg@med.cornell.edu 
 
Roniel Weinberg 
525 East 68th Street, 3rd Floor 
212-746-4303 
row9014@med.cornell.edu  
 
 
 
Nahid Punjani 
525 East 68th Street, Starr 900 
212-746-5470 
212-746-0977 
nap4001@med.cornell.edu 
 
Caroline Kang, MD, PhD 
525 East 68th Street, A 900 
212-746-4739 
cak4005@med.cornell.edu  
 
Jessica Marinaro, MD 
525 E 68th Street, A 900 
212-746-4739 
jam9275@med.cornell.edu  
 
Aaron Brant, MD 
525 East 68th Street, Starr 900 
212-746-5470 
212-746-0977 
aab9038@nyp.org  

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Statistician: 
 
 
 
 
: 
 
Charlene Thomas 
 
 
 
 
 
402 E 67th Street 
 
 
 
 
 
646-962-1645 
 
 
 
 
 
cht2028@med.cornell.edu 
 
 
 
  
 
 
Responsible Research Nurse: 
 
 
 
Study Coordinator & Responsible  
Data Manager: 
 
Kathleen Hart 
 
 
 
Thomas Flynn 
 
525 E 68th St, Suite 900, NYC, NY 10065 
 
 
 
525 E 68th St K901 
 
212-746-5491 
 
 
 
212.746.4739 
 
212-746-8425 
 
 
 
212.746.8778 
 
khart@med.cornell.edu 
 
 
 
thf3001@med.cornell.edu 
 
 
 
 
 
 
Grace Tan  
 
 
 
 
 
525 East 68th Street  
 
 
 
 
 
212.746.3208 
grt2008@med.cornell.edu 
 
Participating Sites:  Weill Cornell Medical College, Department of Urology.  
 
 

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Table of Contents 
STATEMENT OF COMPLIANCE .............................................................................................. VI 
CONFIDENTIALITY STATEMENT ........................................................................................... VII 
LIST OF ABBREVIATIONS .................................................................................................... VIII 
1. PROTOCOL SUMMARY ....................................................................................................... 1 
1.1 
Schema ...................................................................................................................... 2 
1.2 
Study Objectives ........................................................................................................ 3 
1.2.1  
Primary Objectives .............................................................................................. 3 
1.2.2  
Secondary Objectives .......................................................................................... 3 
2. BACKGROUND ................................................................................................................... 3 
2.1 
Disease ...................................................................................................................... 3 
2.2 
Investigational Agent/Device, or Research intervention .............................................. 3 
2.3 
Rationale ................................................................................................................... 4 
2.4 
 Risk/Benefit Assessment ........................................................................................... 4 
2.4.1 
Known Potential Risks ......................................................................................... 4 
2.4.2 
Known Potential Benefits .................................................................................... 5 
2.4.3 
Assessment of Potential Risks and Benefits .......................................................... 5 
2.5 
Correlative Studies Background .................................................................................. 5 
3. STUDY DESIGN ................................................................................................................... 5 
3.1 
Overall Design ............................................................................................................ 5 
3.2 
Scientific Rationale for Study Design ........................................................................... 5 
3.3 
Justification for Dose .................................................................................................. 5 
3.4 
End of Study Definition .............................................................................................. 5 
4. SUBJECT SELECTION ........................................................................................................... 6 
4.1 
Study Population........................................................................................................ 6 
4.2 
Inclusion Criteria ........................................................................................................ 6 
4.3 
Exclusion Criteria ....................................................................................................... 6 
4.4 
Lifestyle Considerations ............................................................................................. 6 
4.5 
Screen Failures ........................................................................................................... 6 
4.6 
Strategies for Recruitment and Retention ................................................................... 7 
5. REGISTRATION PROCEDURES ............................................................................................. 7 
5.1 
Subject Registration (WCM only) ................................................................................ 7 
6. STUDY PROCEDURES .......................................................................................................... 7 
6.1 
Schedule of Assessments ............................................................................................ 7 
6.1.1 
Screening Visit (-7 days before start of Research Intervention) ............................. 8 

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6.1.2 
Intervention Phase (Phase III) .............................................................................. 8 
6.1.2.1 
Visit 1 (end of study) ........................................................................................ 8 
6.1.3 
Follow-up Phase .................................................................................................. 8 
7. STUDY INTERVENTION ....................................................................................................... 8 
7.1 
Study Intervention/Device Description ....................................................................... 8 
7.2 
Availability ................................................................................................................. 8 
7.3 
Acquisition and Accountability ................................................................................... 8 
7.4 
Formulation, Appearance, Packaging, and Labeling ..................................................... 9 
7.5 
Product Storage and Stability ..................................................................................... 9 
Product will be stored at room temperature. ........................................................................ 9 
7.6 
Preparation ................................................................................................................ 9 
7.7 
Dosing and Administration ......................................................................................... 9 
7.7.1 
Dosing Delays/Dose Modifications....................................................................... 9 
7.8 
General Concomitant Medication and Supportive Care Guidelines .............................. 9 
7.9 
Duration of Therapy and Criteria for Removal from Study ......................................... 10 
7.10  Duration of Follow Up ................................................................................................ 10 
7.11 Measures to Minimize Bias: Randomization and Blinding ............................................ 10 
7.12 Study Intervention/Follow-up Compliance .................................................................. 10 
8. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...................................................................................... 10 
8.1 
Discontinuation of Study Intervention ...................................................................... 11 
8.2 
Participant Discontinuation/Withdrawal from the Study .......................................... 11 
8.3 
Lost to Follow Up ..................................................................................................... 11 
10.  MEASUREMENT OF EFFECT ............................................................................................ 12 
10.1 Response Criteria ....................................................................................................... 12 
11. DATA REPORTING / REGULATORY CONSIDERATIONS ...................................................... 12 
11.1 Data Collection ........................................................................................................... 12 
11.1.1 REDCap ................................................................................................................ 13 
11.2 Regulatory Considerations .......................................................................................... 13 
11.2.1 Institutional Review Board/Ethics Committee Approval ........................................ 13 
11.2.2 Ethical Conduct of the Study ................................................................................ 14 
11.2.3 Informed Consent ................................................................................................ 14 
11.2.4 Compliance with Trial Registration and Results Posting Requirements .................. 14 
11.2.5 Record Retention ................................................................................................. 14 
12.1 Study Design/Endpoints.............................................................................................. 14 
12.2 Statistical Analysis ...................................................................................................... 15 
12.5 Interim Analysis .......................................................................................................... 16 
12.6 Reporting and Exclusions ............................................................................................ 16 
12.6.1 Evaluation of Toxicity ........................................................................................ 16 

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13. ADVERSE EVENT REPORTING REQUIREMENTS ................................................................ 16 
13.1 Adverse Event Definition ............................................................................................ 17 
13.1.1 Investigational Agent or Device Risks (Expected Adverse Events) ....................... 17 
13.1.2 Adverse Event Characteristics and Related Attributions ..................................... 17 
13.1.3 Recording of Adverse Events ............................................................................. 17 
13.1.4 Reporting of AE to WCM IRB .............................................................................. 17 
13.2 Definition of SAE ........................................................................................................ 18 
13.2.1 Reporting of SAE to IRB ..................................................................................... 18 
13.2.2 Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor-Investigator]
 
18 
13.2.3 Reporting of SAE to Curis Pharmacy ................................................................... 18 
13.3 AE/SAE Follow Up ....................................................................................................... 18 
13.4 Time Period and Frequency for Event Assessment and Follow Up ................................ 18 
14. UNANTICIPATED PROBLEMS INVOLVING RISKS TO SUBJECTS OR OTHERS........................ 19 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSO) 19 
14.1.2 Unanticipated Problem Reporting...................................................................... 19 
15. DATA AND SAFETY MONITORING PLAN (DSMP) .............................................................. 20 
REFERENCES ........................................................................................................................ 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Statement of Compliance 
 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the WCMC 
Institutional Review Board (IRB) Terms and Conditions of Award. The Principal Investigator will assure that 
no deviation from, or changes to the protocol will take place without prior agreement from the 
Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsor, funding agency and 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval.  Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  All changes to the consent form 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 
 
 
 
 

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Confidentiality Statement 
 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, and applicable independent ethics committees or institutional 
review boards. The contents of this document shall not be disclosed to others without written 
authorization from WCMC. 
 
 
 
 
 
 
 
 
 
 
 
 

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List of Abbreviations 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTSC 
Clinical Translational Science Center  
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety Monitoring Plan 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HRBFA 
Human Research Billing Analysis Form 
HUD 
Humanitarian Use Device  
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption  
IND 
Investigational New Drug 
IRB 
NRS-11 
Institutional Review Board 
Numerical Pain Score  
PHI 
Protected Health Information 
PI 
Principal Investigator 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
UIRTSO 
Unanticipated Problem Involving Risks to Subjects or Others 
WCM 
Weill Cornell Medicine 

Protocol # 19-08020686 
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1. Protocol Summary 
 
Full Title: 
 
 
 
 
Multi-modal Analgesia to Reduce Narcotics After Scrotal Surgery  
Short Title:  
 
 
 
Narcotic Reduction After Surgery  
Clinical Phase:  
 
 
III 
Principal Investigator:  
 
Jessica Marinaro 
Study Description:  
 
The use of non-narcotic multi-modal analgesia to be used in the pre-
operative, peri-operative and post-operative period to reduce or 
potentially eliminate narcotic usage following scrotal surgery. We have 
shown that the use of anti-inflammatories in the peri-operative period 
reduce both pain and narcotic use. Our hypothesis is that adding 
another agent in the multi modal pathway will further reduce pain and 
potentially reduce narcotic usage. 
Sample Size: 
 
N= 86 (43 participants in each arm) 
Enrollment: 
 
This study will enroll 86 participants but will screen 114 participants 
accounting for an approximate 25% screening failure rate.   
Study Population: 
 
Participants undergoing microsurgical testicular sperm extraction for 
non-obstructive azoospermia. 
Enrollment Period: 
 
2 years.  
Study Design: 
 
Double-blind, placebo-controlled, randomized trial 
 
 
Two study arms (43 participants per arm) 
 
 
Addition of gabapentin pre- and post-operatively 
Description of Sites/  
Facilities Enrolling 
Participants: 
 
This will be a single center study at Weill Cornell Medicine/New York 
Presbyterian Hospital.    
Study Duration: 
 
December 31, 2023 
Participant Duration: 
 
7 days. 
Study Agent/Device Name  
Intervention Description: 
Arm #1 – Gabapentin 600mg taken pre-operatively and 300mg taken 
three times a day for 3 days.  
 
 
Arm #2 – Placebo taken pre-operatively and three times a day for 3 
days. 
 
 
  
Primary Objective: 
 
Pain scores 
Secondary Objectives:  
Narcotic consumption 
Exploratory Objectives:  
Symptom modification (ie. nausea) 
Endpoints: 
 
Numerical pain rating scale 
 
 
Narcotic prescription usage 
 
 
 
 
 

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1.1 Schema 
 
 
 
 
 
Prior to 
Enrollment 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N= 86 Participants: Obtain informed consent. Screen potential participants by 
inclusion and exclusion criteria; obtain history, document. 
Pre-operative assessment 
Refer to Section 6.1, Schedule of Assessments 
Administer initial medication 2 hours before surgery  
Participant present for routine post-operative visit 2-3 weeks after surgery. 
Blinding will be revealed. 
Screen for adverse events. 
Arm 2 
43 Participants 
Arm 1 
43 Participants 
Medication administration for 3 days, three times a day. 
Online surveys (through REDCap) 
Randomize 

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1.2 Study Objectives 
 
 
 
 
1.2.1  Primary Objectives  
 
To compare participant reported pain between participants receiving gabapentin and 
those receiving placebo in addition to standard of care. This will be assessed using the 
11-point numerical pain rating scales (NRS-11) from post-operative day 1 to 7. 
 
1.2.2  Secondary Objectives  
 
 To assess narcotic use following surgery including the number of tablets taken, 
frequency and time when narcotic is initially utilized. Study participants satisfaction will 
be documented. 
 
2. Background 
 
2.1 Disease 
 
Microdissection testicular sperm extraction (microTESE) is the gold standard for sperm 
retrieval in research study participants with non-obstructive azoospermia for in vitro 
fertilization.1 Scrotal and testicular surgery can be associated with post-operative pain and 
improper narcotic utilization has become a significant societal problem.2  
 
2.2 Investigational Agent/Device, or Research intervention 
 
Multi-modal analgesia has been used as an alternative to reduce narcotic usage in the peri-
operative and post-operative period following scrotal surgery. Our previous work has 
looked at the role of anti-inflammatories, specifically COX-2 inhibitors, for this purpose and 
has shown a reduction in both post-operative pain and narcotic usage.3 The addition of 
other non-narcotic analgesics may reduce and potentially eliminate narcotic usage following 
scrotal surgery. 
 
Gabapentin is a well-known anti-convulsant medication that is commonly used by pain 
specialists in their approach to multi-modal pain control.4 It is most often used to treat 
neuropathic pain often characterized by a burning or itching cessation and may be related 
to diseases such as diabetes.5  
 
Gabapentin is a ligand of the a2delta subunit of voltage gated calcium channels, but the 
mechanism of action by which gabapentin facilities pain reduction is unclear, various 
hypotheses exist including reduced hyperexcitability of neurons resulting in central 
desensitization, decreased calcium entry caused by binding to the dorsal horn neurons 
reducing neurotransmitter release or through other channels such as sodium or NMDA 
channels.6 Gabapentin is water soluble and rapidly absorbed with dose-dependent 
bioavailability, with a half-life of approximately 5-7 hours.7 For this reason it is commonly 
dosed up to three times per day. It is cleared renally, and not metabolized and has no 

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impact on hepatic enzymes.8 The medication is generally well tolerated with the most 
common effects of somnolence and dizziness, and does not need to be taken with meals.9 
 
Previous studies have examined the role of gabapentin for relief of acute pain in the peri-
operative period. Studies in the plastic surgery literature, obstetrical literature, general 
surgery literature and orthopedic literature have examined its use with varying impacts.10-12 
Various doses and schematics for administration have been studied, including meta-
analyses, which show conflicting results.10 Doses have been reported from 300mg-1200mg 
in these studies, and given before surgery and for a short duration afterwards. Some studies 
have also studied the combination of celecoxib with gabapentin showing an improved 
benefit in both pain scores, as well as side effect reduction.13 A lack of robust, large and well 
controlled trials have been completed.11 
 
Overall gabapentin has been shown to have minimal drug interactions due to its 
pharmacokinetics. Studies that have been completed often show varied results.14 
 
Gabapentin is a FDA approved medication prescribed for the treatment of partial or focal 
seizures in adults and children, and for the management of post-herpetic neuralgia. The use 
of gabapentin in this study is considered investigational (ie. it is used for an unapproved 
indication). Investigators seek an IND exemption as the study uses gabapentin to assess pain 
reduction and gabapentin consumption after scrotal surgery. This study does NOT intend to 
support a significant change in the advertising for a prescription product, FDA approval of a 
new indication or a significant change in the product labeling, or FDA approval of change in 
route of administration, dose, and/or patient population.  
 
 
 
2.3 Rationale 
 
Pain management is an ongoing issue for all surgeons, and with rising concerns regarding 
opioid addiction and consumption, multi-modal strategies and alternatives are necessary.2 
Given that we have previously shown the role of anti-inflammatory medications reducing 
narcotic usage in the peri-operative period in addition to acetaminophen, we believe 
addition of another agent may reduce narcotic use completely.3 No literature to our 
knowledge is available regarding the use of gabapentin in urologic surgery, and given its 
potential benefit in other surgeries we believe this will further reduce pain and possibly 
eliminate narcotic usage post scrotal surgery. 
 
2.4  Risk/Benefit Assessment  
 
 
2.4.1 
Known Potential Risks 
 
As per the FDA, gabapentin side effects commonly include dizziness and drowsiness. 
Other reported adverse events include headache, lack of coordination, viral infection, 
nausea and vomiting, difficulty speaking, tremor, swelling, fever, jerky movements, 
difficulty with coordination, double vision and unusual eye movement.  
 

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2.4.2 
Known Potential Benefits  
 
 
 
 
The benefits of the medication include known research showing improved pain control 
in certain populations. This could potentially reduce narcotic consumption and reduce 
costs associated with narcotic dependence and addiction.  
 
2.4.3 
Assessment of Potential Risks and Benefits 
 
 
The research intervention has numerous health benefits to the individuals who will be 
participating in the study. Improved health outcomes are expected due to the research intervention 
such as better pain control in scrotal and urologic surgery, and clinical practice pertaining to reduced 
prescription and consumption of narcotics amongst patients with non-obstructive azoospermia 
undergoing scrotal surgery.    
 
2.5 Correlative Studies Background 
 
 
 
 
Not applicable 
 
3. Study Design 
 
3.1 Overall Design 
 
This will be assessed in a phase III randomized, double-blind control trial. All eligible subjects will be 
included and enrolled sequentially from the study start date. The study will include two arms 
(gabapentin or placebo) at a single site in patients undergoing microsurgical testicular sperm 
extraction.  
 
3.2 Scientific Rationale for Study Design 
 
This study will use two arms to study the efficacy of gabapentin. A placebo will be used in order to 
blind the participants to reduce bias. The study will be designed to test superiority compared to 
placebo. The potential problems relate to the side effects of the medications themselves, otherwise 
all participants will receive sufficient analgesia in order to control their post-operative pain. 
 
3.3 Justification for Dose  
 
The dose for gabapentin will be in keeping with data from the literature and routine clinical practice. 
Various studies have examined doses from 300mg-1200mg, and while some have shown increased 
effects at maximal doses this is also associated with more side effects.15,16 Given the outpatient 
nature of this procedure and many scrotal surgeries, dosing on the lower end was more justified 
with 600mg given 2 hours before surgery, and 300mg three times a day for 3 days. 
 
3.4 End of Study Definition 
 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last pain score assessment and record of narcotic consumption on post-

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operative day #7 as shown in the Schedule of Assessments (SoA), Section 6.1. The end of the study is 
defined as return of the pain score and narcotic consumption at post-operative follow-up visit. 
 
4. Subject Selection 
 
4.1 Study Population 
 
Subjects undergoing microsurgical sperm extraction who meet the inclusion and exclusion criteria 
will be offered participation in this study.   
 
4.2 Inclusion Criteria 
 
 
1. Participants undergoing microsurgical testicular sperm extraction 
 
2. Participants over 18 years of age who can provide informed consent 
3. Participants with no contraindication to the consumption gabapentin or documented 
allergy/intolerance 
4. Participants not currently using opiates for another reason 
 
 
4.3 Exclusion Criteria  
 
 
 
 
1. Contraindication to the consumption of celecoxib or gabapentin 
 
2. History of substance abuse (including prior opiate abuse) 
 
3. Narcotic use within last 3 months 
4. Any of the following comorbidities: renal failure, heart disease, peptic ulcer disease, 
cerebrovascular disease, significant liver disease, untreated depression, chronic pain disorder, or 
bleeding diatheses 
5. Medical history or concurrent illness that the investigator considers sufficiently serious to 
interfere with the conduct, completion, or results of this trial, or constitutes an unacceptable risk to 
the subject 
 
4.4 Lifestyle Considerations 
 
Not applicable. 
 
4.5 Screen Failures  
 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study intervention or entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, 
to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any serious adverse event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of an 
inability to take either study drug may be rescreened. Rescreened participants should be assigned 
the same participant number as for the initial screening. 
 

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4.6 Strategies for Recruitment and Retention 
 
 
 
Participants will be recruited sequentially as any patient undergoing microsurgical testicular sperm 
extraction at Weill Cornell/New York Presbyterian Hospital by Dr. Peter N. Schlegel. All participants 
over 18 years of age will be considered. 
 
We anticipate an accrual rate of 80% from a single site. These study participants will be recruited in 
the clinic at the time of surgical consent. 
 
Participants will be identified and approached by a member of the research team. 
 
Participants will not receive any compensation for their participation in the study. 
 
 
5. Registration Procedures 
 
5.1 Subject Registration (WCM only) 
 
Subjects will be registered within the WRG-CT as per the standard operating procedure for 
Subject Registration.  
 
 
 
 
6. Study Procedures 
 
6.1 Schedule of Assessments 
 
Table 1. Schedule of trial events 
   
Pre-
Study 
Day of 
Surgery 
POD 
#1 
POD 
#2 
POD 
#3 
POD 
#7 
Off 
Study 
 
Agent 
Administration  
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concurrent meds 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Outcome Evaluation  
(Pain Scores) 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
Outcome Evaluation 
(Narcotic Usage) 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 

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6.1.1 
Screening Visit (-7 days before start of Research Intervention) 
 
• 
Informed consent  
• 
Medical history 
• 
Medication history 
 
 
 
 
6.1.2 
Intervention Phase (Phase III) 
 
 
 
 
  
Eligible subjects will be randomly assigned to one of the arms using a computer-
generated randomization scheme developed by the data manager.   
 
 
6.1.2.1 Visit 1 (end of study) 
 
 
 
 
 
Collection of pain score questionnaires and narcotic consumption. 
 
 
 
6.1.3 
Follow-up Phase 
 
 Participant recorded questionnaires and data will be obtained at the standard surgical 
follow-up visit. 
 
7. Study Intervention 
 
7.1 Study Intervention/Device Description   
 
 
Gabapentin will be prepared in a capsule format. It will be shipped to the PI’s address at Weill  
 
Cornell. The drug may be stored at room temperature which will be indicated on the product label.  
 
 
The placebo will also be prepared in a capsule format. It will be shipped to the PI’s address at Weill  
 
Cornell. The drug may be stored at room temperature which will be indicated on the product label. 
 
 
The exact shipping address is below: 
 
Research Pharmacy #PH# 
NewYork-Presbyterian Hospital/Weill Cornell Medical Center 
525 E. 68th St., Room F06 
New York, NY 10065 
 
7.2 Availability 
 
The use of gabapentin in this study is considered investigational as it is used for an 
unapproved indication. 
Gabapentin is an investigational agent supplied to investigators by Curis Pharmacy. 
 
7.3 Acquisition and Accountability  
 
 
 
Contact person: 

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Nicole @ Curis Pharmacy  
1853 S Dixie Highway  
Pompano Beach, FL  
33060 
 
Phone: 855 472 1894- Fax 800 419 2801. 
 
Time necessary to fill order depends on quantity needed. Two day priority shipping is available. 
 
Agent Inventory Records/Device Logs – The investigator, or a responsible party designated by the 
investigator, will maintain a careful record of the inventory and disposition of all agents/device 
received from Sponsor on a Drug Accountability Record Form (DARF) or Device Log.  
 
7.4 Formulation, Appearance, Packaging, and Labeling  
 
Both the gabapentin and placebo will be identical appearing capsules. The appearance will be blue 
Opaque capsules. The packing will vary based on quantity ordered (ie. larger quantities will be sent 
in unguator jars). Pills will be labelled generically to ensure blinding. 
 
7.5 Product Storage and Stability 
 
Product will be stored at room temperature. 
 
7.6 Preparation 
 
      No preparation is needed, the capsules are ready for oral use. 
 
7.7 Dosing and Administration 
 
Each participant will receive the same dose of the drug.  
 
Gabapentin will be administered as a single dose pre-operatively 600 mg and then 300mg three 
times a day for three post-operatively.  
 
Placebo medication will be administered in the same fashion. 
 
7.7.1 
Dosing Delays/Dose Modifications 
 
If a subject demonstrates side effects, the dose will be reduced to half. If there is a significant 
adverse event, the drug will no longer be administered.  
 
7.8 General Concomitant Medication and Supportive Care Guidelines 
 
All concomitant medications will be recorded and/or updated on subject medication log in keeping 
with routine clinical practice and saved in subject binder, if applicable. 
 

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7.9 Duration of Therapy and Criteria for Removal from Study 
 
In the absence of delays in administration of the investigational drug due to adverse event(s), drug 
administration may continue in the post-operative period for three days addition to the pre-
operative period. Other reasons may include: 
 
o 
Intercurrent illness that prevents further administration of investigational drug, 
o 
Unacceptable adverse event(s) 
o 
Subject decides to withdraw from the study, or 
o General or specific changes in the subject’s condition render the subject unacceptable for 
further administration of drug in the judgment of the investigator 
 
7.10  Duration of Follow Up 
 
Subjects will be followed until their first post-operative visit, at which time they will be removed 
from the study, or until death, whichever occurs first.  Subjects removed from study for 
unacceptable adverse events will be followed until resolution or stabilization of the adverse event.  
 
7.11 Measures to Minimize Bias: Randomization and Blinding  
 
 
Permuted blocked randomization will be performed.  A series of randomized blocks with a defined 
block size will be generated with a 1:1 allocation ratio to allow for an equal number of participants in 
the study drug and placebo groups.  A statistician from the Weill Cornell CTSC Biostatistics, 
Epidemiology and Research Design (BERD) Core will create the randomization list and will not be 
involved with the study statistician(s).  The randomization list will also reside in the Research 
Pharmacy.  Only the BERD statistician and the Research Pharmacy will have a copy of the blocked 
randomization list and will know the true meaning of the block assignments.  If unbinding is 
necessary, the BERD statistician (or Research Pharmacy) can immediately determine whether or not 
the participant received the study drug or placebo. 
 
7.12 Study Intervention/Follow-up Compliance 
 
Study participant adherence will be completed in the form of a reminder phone call. Participants 
will be required to complete questionnaires for a visual analogue scale as well as daily narcotic 
usage.  
 
Participants will be seen for their study materials at their usual post-operative follow-up visit. 
Two attempts will be made to contact the subject if they do not return for their follow-up visit 
or provide the necessary study documents, at which point the subject will be considered “lost to 
follow-up” and no longer participating in the study. 
 
8. Study Intervention Discontinuation and Participant Discontinuation/Withdrawal 
 
Participants may withdraw voluntarily from the study or the PI may discontinue a participant from the 
study at any time. The following adverse events would necessitate discontinue of the study intervention 
or participant discontinuation/withdrawal: 
 

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• 
Drug Reaction with Eosinophilia and Systemic Symptoms (Multiorgan hypersensitivity) 
• 
Anaphylaxis and Angioedema 
• 
Severe Somnolence/Sedation and Dizziness 
• 
Suicidal Behavior and Ideation 
 
Participants may discontinue the study intervention, but remain in the study for follow-up, especially for 
safety and efficacy study endpoints (if applicable). 
 
 
8.1 Discontinuation of Study Intervention 
 
Discontinuation from gabapentin administration does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study protocol.  If a clinically 
significant finding is identified (including, but not limited to changes from baseline) after enrollment, 
the investigator or qualified designee will determine if any change in participant management is 
needed. Any new clinically relevant finding will be reported as an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
Post-operative follow-up to ensure any adverse event resolution 
 
8.2 Participant Discontinuation/Withdrawal from the Study 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Significant study intervention non-compliance  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Participant unable to receive the medication 
• 
Participant lost to follow-up after several attempts to contact subject to schedule study visit. 
Subjects will be medically monitored by clinicians in the research team for detection of any adverse 
events. The reason for participant discontinuation or withdrawal from the study will be recorded on 
the Case Report Form (CRF). Subjects who sign the informed consent form and are randomized but 
do not receive the study intervention may be replaced.  Subjects who sign the informed consent 
form, and are randomized and receive the study intervention, and subsequently withdraw, or are 
withdrawn or discontinued from the study, will not be replaced. 
8.3 Lost to Follow Up 
 
 A participant will be considered lost to follow-up if he or she fails to return for 1 scheduled visits 
and is unable to be contacted by the study site staff following 2 attempts.  

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The following actions must be taken if a participant fails to return to the clinic for a required study 
visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit within 4 weeks 
and counsel the participant on the importance of maintaining the assigned visit schedule and 
ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 2 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the participant’s medical record or study file.  
• 
Should the participant continue to be unreachable, he will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
 
 
 
10.  Measurement of Effect 
 
Effect of pain will be measured using the validated numerical rating scale. 
 
Narcotic consumption will be recorded as a numerical value. 
 
10.1 Response Criteria 
 
 
The study participants will be prompted to complete online surveys administered through 
REDCap. The REDCap database allows for HIPAA compliant data gathering through this format.  
Each survey will include the following: a numerical rating scale (0 through 11) to rank current 
pain, number of narcotic tablets consumed since the prior survey, overall satisfaction of pain 
control (binary yes/no) as well documentation of other related symptoms (ie. nausea).  
 
 
 
11. Data Reporting / Regulatory Considerations 
 
11.1 Data Collection 
 
The data collection plan for this study is to utilize REDCap to capture all research intervention 
procedures outlined in the protocol, toxicity, efficacy, and adverse event data for all enrolled 
study participants. To ensure maximum compliance, subjects will be prompted by email, phone, 
or with a text message to their mobile phone. To ensure HIPAA compliance, text messages will 
only read as “A new survey is due.” Participants will be informed of this prompting protocol 
beforehand. No PHI, or any details of medical therapy, will be revealed in the text message or in 
the surveys administered through REDCap (please see the survey attachment to review how 
each survey will appear). Texts will be sent from a study dedicated phone controlled by the 
study staff.  The study phone will be encrypted and managed by ITS per WCM regulation. 
Subjects will complete surveys at the following intervals: every 8 hours post-operative day 1 and 
2, Every 12 hours post-operative day 3 through 7. 
 

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11.1.1 REDCap 
 
REDCap (Research Electronic Data Capture) is a free data management software system 
that is fully supported by the Weill-Cornell Medical Center CTSC.  It is a tool for the 
creation of customized, secure data management systems that include Web-based data-
entry forms, reporting tools, and a full array of security features including user and 
group based privileges, authentication using institution LDAP system, with a full audit 
trail of data manipulation and export procedures.  REDCap is maintained on CTSC-
owned servers that are backed up nightly and support encrypted (SSL-based) 
connections.  Nationally, the software is developed, enhanced and supported through a 
multi-institutional consortium led by the Vanderbilt University CTSA. 
 
11.2 Regulatory Considerations 
 
11.2.1 Institutional Review Board/Ethics Committee Approval  
 
As required by local regulations, the Investigator will ensure all legal aspects are covered, and 
approval of the appropriate regulatory bodies obtained, before study initiation.  
Before initiation of the study at each study center, the protocol, the ICF, other written material 
given to the study participants, and any other relevant study documentation will be submitted to 
the appropriate Ethics Committee. Written approval of the study and all relevant study 
information must be obtained before the study center can be initiated or the IP is released to the 
Investigator. Any necessary extensions or renewals of IRB approval must be obtained for changes 
to the study, such as amendments to the protocol, the ICF, or other study documentation. The 
written approval of the IRB together with the approved ICF must be filed in the study files.  
The Principal Investigator will report promptly to the IRB any new information that may adversely 
affect the safety of the study participants or the conduct of the study. The Investigator will submit 
written summaries of the study status to the IRB as required. On completion of the study, the IRB 
will be notified that the study has ended.  
 
All agreed protocol amendments will be clearly recorded on a protocol amendment form and will 
be signed and dated by the original protocol approving signatories. All protocol amendments will 
be submitted to the relevant institutional IRB for approval before implementation, as required by 
local regulations. The only exception will be when the amendment is necessary to eliminate an 
immediate hazard to the trial participants. In this case, the necessary action will be taken first, 
with the relevant protocol amendment following shortly thereafter.  
Once protocol amendments or consent form modifications are implemented at the lead site, Weill 
Cornell Medicine, updated documents will be provided to participating sites, as applicable. Weill 
Cornell Medicine must approve all consent form changes prior to local IRB submission.  
Relevant study documentation will be submitted to the regulatory authorities of the participating 
countries, according to local/national requirements, for review and approval before the beginning 
of the study. On completion of the study, the regulatory authorities will be notified that the study 
has ended.  
 

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11.2.2 Ethical Conduct of the Study  
The Investigators and all parties involved should conduct this study in adherence to the ethical 
principles based on the Declaration of Helsinki, GCP, ICH guidelines and the applicable national 
and local laws and regulatory requirements.  
 
This study will be conducted under a protocol reviewed and approved by the applicable ethics 
committees and investigations will be undertaken by scientifically and medically qualified 
persons, where the benefits of the study are in proportion to the risks. 
 
11.2.3 Informed Consent 
 
The investigator or qualified designee must obtain documented consent according to ICH-GCP 
and local regulations, as applicable, from each potential subject or each subject’s legally 
authorized representative prior to participating in the research study. Subjects who agree to 
participate will sign the approved informed consent form and will be provided a copy of the signed 
document.   
 
The initial ICF, any subsequent revised written ICF and any written information provided to the 
subject must approved by IRB prior to use. The ICF will adhere to IRB requirements, applicable 
laws and regulations. 
 
11.2.4 Compliance with Trial Registration and Results Posting Requirements  
 
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the Food 
and Drug Administration Amendments Act (FDAAA), the Sponsor-Investigator of the trial is solely 
responsible for determining whether the trial and its results are subject to the requirements for 
submission to http://www.clinicaltrials.gov. Information posted will allow subjects to identify 
potentially appropriate trials for their disease conditions and pursue participation by calling a 
central contact number for further information on appropriate trial locations and trial site contact 
information. 
 
11.2.5 Record Retention 
 
Essential documents are those documents that individually and collectively permit evaluation of 
the study and quality of the data produced.  After completion of the study, all documents and 
data relating to the study will be kept in an orderly manner by the Investigator in a secure study 
file.  In addition, all subjects’ medical records and other source documentation will be kept for the 
maximum time permitted by the hospital, institution, or medical practice. Research records will 
be kept for at six years after the end of the study.   
 
12. Statistical Considerations 
 
 
12.1 Study Design/Endpoints 
 

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The study will be a randomized double blind placebo controlled trial. We will randomize 86 study 
participants into two arms, with equal numbers in each arm. 
 
Both the control arm and intervention arm will receive medication to be taken 2 hours before 
surgery as well as for three days three times a day after surgery. The team will be blinded to 
medication each study participant is receiving and will be recorded using a subject coded system. 
 
Participants will receive reduced oxycodone prescriptions (quantity to be determined by clinical 
practice and prescribing surgeon) as needed, as well as celecoxib and acetaminophen to be taken as 
prescribed for the peri-operative period and up to 7 days post-operatively. 
 
During the 7 subsequent post-op days participants in both the intervention and control arms will be 
asked to maintain a pain diary.  The diary will be implemented online through the REDCap platform, 
which allows for secure online surveys. To ensure maximum compliance, subjects will be prompted 
by email, phone, or with a text message to their mobile phone. To ensure HIPAA compliance, text 
messages will only read as “A new survey is due.” Participants will be informed of this prompting 
protocol beforehand. No PHI, or any details of medical therapy, will be revealed in the text message 
or in the surveys administered through REDCap (please see the survey attachment to review how 
each survey will appear). Texts will be sent from a study dedicated phone controlled by the study 
staff.  The study phone will be encrypted and managed by ITS per WCM regulation. Subjects will 
complete surveys at the following intervals: every 8 hours post-operative day 1 and 2, Every 12 
hours post-operative day 3 through 7. 
 
Participants will be monitored for adverse events by the pre-operative nurses as well as the post-
operative anesthesia care nurses who will be counselled on symptoms to examine for. Participants 
will have the opportunity to document any adverse events on their surveys. 
 
Our primary endpoint will be to compare participant reported pain between participants receiving 
gabapentin and those receiving placebo in addition to standard of care. This will be assessed using 
the 11-point numerical pain rating scales (NRS-11) from post-operative day 1 to 7.  
 
Our secondary endpoints include narcotic use following surgery including the number of tablets 
taken, frequency and time when narcotic is initially utilized. Participant satisfaction will be 
documented. Reduction in other symptoms such as nausea will also be recorded. 
 
12.2 Statistical Analysis 
 
The primary objective of this double-blind, placebo controlled randomized trial is to compare the 
participant-reported pain scores taken on an 11-point numerical rating scale (NRS-11) between 
subjects who received Gabapentin and controls who received placebo on day-7 post-scrotal surgery.  
The secondary objective is to determine whether the addition of gabapentin for post-operative pain 
control reduces narcotic intake. This study will also explore the effect gabapentin has on symptom 
modification. 
 
Assuming a baseline NRS-11 score of 3.8 (from previous study) and a goal is to detect a two-point 
difference (reduction) in the day-7 pain score between the two groups, a sample size of 86 
participants (43 per arm) will yield a power of 80% when using a two-sample t-test with a 0.05 two-

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sided significance level.  To account for potential loss to follow up and drop-out at a rate of 25%, 
each arm will require 43 study participants for a total recruitment of 86 study participants. This 
calculation assumes a standard deviation of 2.9, which is based on a previous study that looked at 
the effect of celecoxib in the same patient setting.3  
 
Approximately 150 to 250 microTESE procedures are conducted at our site annually. As a result, we 
plan to accrue and complete the study in 29 months (i.e. ~9 study participants per month). 
 
Descriptive statistics will be calculated to describe the cohort of study participants using N (%) and 
mean, median, range for categorical and continuous factors, respectively.  A two-sample t-test or 
nonparametric Wilcoxon rank-sum test will be used, as appropriate, to compare the mean (median) 
participant-reported pain scores on day 7 post-scrotal surgery between the two arms. A chi-square 
test or Fisher’s exact test will be used, as appropriate, to compare the proportion of narcotic use 
post-scrotal surgery between the two arms and to compare the proportion of adverse events 
experienced post-scrotal surgery between the two arms. Similar analyses will also be completed on 
the NRS-11 pain score, narcotic use, and reported adverse events on day-1 post-scrotal surgery. 
Generalized estimating equations (GEE) modeling will also be performed to compare NRS pains 
scores, assessed over all post-operative days 1 to 7, between the gabapentin and placebo groups.  
GEE allows for multiple observations per participant (i.e., pain scores for day 1 to day 7, per 
participant) and also allows for the incorporation of missing pain scores at some of the defined time 
points. 
 
All p-values will be two-sided with statistical significance evaluated at the 0.05 alpha level.  Ninety-
five percent confidence intervals for all parameters of interest will be calculated to assess the 
precision of the obtained estimates.  All analyses will be performed in R Version 3.6.1 (R Foundation 
for Statistical Computing, Vienna, Austria).  Note: The statistical considerations section was written 
in conjunction with Charlene Thomas, MS, in the Division of Biostatistics and Epidemiology, 
Department of Healthcare Policy & Research. 
 
12.5 Interim Analysis 
 
No interim analysis for efficacy will be performed.  
 
 12.6 Reporting and Exclusions 
 
12.6.1 Evaluation of Toxicity 
 
The frequency of subjects experiencing toxicities in each research study arm will be 
tabulated.  Toxicities will be assessed and graded according to CTCAE v. 5.0 terminology.  Exact 
95% confidence intervals around the toxicity proportions will be calculated to assess the 
precision of the obtained estimates. 
 
 
13. Adverse Event Reporting Requirements  
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The investigator will 
be required to provide appropriate information concerning any findings that suggest significant hazards, 

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contraindications, side effects, or precautions pertinent to the safe use of the drug or device under 
investigation.  Safety will be monitored by evaluation of adverse events reported by subjects or 
observed by investigators or research staff, as well as by other investigations such as clinical laboratory 
tests, x-rays, electrocardiographs, etc. 
 
13.1 Adverse Event Definition 
 
An adverse event (also referred to as an adverse experience) can be any unfavorable and unintended 
sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
drug, and does not imply any judgment about causality. An adverse event can arise with any use of the 
drug (e.g., off-label use, use in combination with another drug) and with any route of administration, 
formulation, or dose, including an overdose.  
 
 
13.1.1 Investigational Agent or Device Risks (Expected Adverse Events) 
 
Gabapentin is a medication known to treat seizures. It does have known adverse events 
especially when taken at high doses. As per the FDA in participants taking gabapentin for pain, 
side effects occurring >8% of the time compared to placebo include dizziness, somnolence, and 
peripheral edema. Other side effects were seen in less than 5% including asthenia, GI symptoms, 
weight gain, abnormal thinking, incoordination, ataxia, or ocular symptoms.  
 
 
13.1.2 Adverse Event Characteristics and Related Attributions 
 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in the 
revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized 
for AE reporting.  A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov). 
 
• 
Attribution of the AE: 
- Definite – The AE is clearly related to the research intervention. 
- Probable – The AE is likely related to the research intervention. 
- Possible – The AE may be related to the research intervention. 
- Unlikely – The AE is doubtfully related to the research intervention. 
- Unrelated – The AE is clearly NOT related to the research intervention. 
 
 
 
13.1.3 Recording of Adverse Events 
 
All adverse events will be recorded on a subject specific AE log. The AE log will be maintained by 
the research staff and kept in the subject’s research chart.    
 
 
13.1.4 Reporting of AE to WCM IRB 
 
All AEs occurring on this study will be reported to the IRB according to the IRB policy, which can 
be accessed via the following link:  
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting_Poli
cy.pdf.  

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13.2 Definition of SAE 
 
SAEs include death, life threatening adverse experiences, hospitalization or prolongation of 
hospitalization, disability or incapacitation, overdose, congenital anomalies and any other 
serious events that may jeopardize the subject or require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  
 
13.2.1 Reporting of SAE to IRB 
 
All SAEs occurring on this study will be reported to the IRB according to the IRB policy, which can 
be accessed via the following link:   
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting_Poli
cy.pdf.  
 
13.2.2 Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor-Investigator] 
 
If an SAE occurs on this study, the event will be filed on a MedWatch form with the FDA. The 
investigator must notify the FDA of any SAE’s as soon as possible but no later than 7 calendar 
days after the initial receipt of the information 
 
CDER INDs:  
Food and Drug Administration 
Center for Drug Evaluation and Research 
5901-B Ammendale Road  
Beltsville, MD 20705-1266  
 
13.2.3 Reporting of SAE to Curis Pharmacy 
 
Not applicable. 
 
 
13.3 AE/SAE Follow Up 
 
 All SAEs and AEs reported during this study will be followed until resolution or until the investigator 
confirms that the AE/SAE has stabilized and no more follow-up is required. This requirement indicates 
that follow-up may be required for some events after the subject discontinues participation from the 
study.  
 
13.4 Time Period and Frequency for Event Assessment and Follow Up 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 

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All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The primary investigator will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
14. Unanticipated Problems Involving Risks to Subjects or Others 
 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSO) 
 
 The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
 
 
14.1.2 Unanticipated Problem Reporting 
 
The investigator will report unanticipated problems (UPIRTSOs) to the reviewing Institutional 
Review Board (IRB) and to the Data Coordinating Center (DCC)/lead principal investigator (PI). 
The UPIRTSO report will include the following information: 
 

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• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB 
project number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UPIRTSO;  
• 
A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UPIRTSO. 
 
To satisfy the requirement for prompt reporting, UPIRTSOs will be reported using the following 
timeline:   
 
• 
UPIRTSOs that are serious adverse events (SAEs) will be reported to the IRB and to the 
DCC/study sponsor within <insert timeline in accordance with policy> of the investigator 
becoming aware of the event.  
• 
Any other UPIRTSO will be reported to the IRB and to the DCC/study sponsor within 
<insert timeline in accordance with policy> of the investigator becoming aware of the 
problem.  
• 
All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or designee), 
Food and Drug Administration (FDA), and the Office for Human Research Protections 
(OHRP) within <insert timeline in accordance with policy> of the IRB’s receipt of the 
report of the problem from the investigator. 
 
 
15. Data and Safety Monitoring Plan (DSMP) 
 
 
• 
Adverse events will be recorded by the study nurse and clinical fellow during follow-up 
phone calls and clinic visits with each post-operative patient.  Minor adverse events will 
be examined and reviewed for intervals of every 10 subjects during accrual.  Any 
significant adverse events or grade 4 events possibly related to the study product will 
trigger a temporary cessation of the trial and full review by the principal investigator, as 
well as the WCM DSMB as to whether the study should continue.  
 
• 
The WCM DSMB will be utilized in our investigator-initiated study, with evaluation of 
adverse events at specific intervals. This will occur at 6 month time periods. 
 
• 
Data 
o Adverse event data 
▪ Major: Allergic reaction, suicidal behavior and ideation, driving 
impairment 
▪ Minor: dizziness, somnolence, peripheral edema, ataxia, fatigue, 
nystagmus, GI symptoms 
o Study-related data 
▪ Pain scores (NRS-11), Narcotic tablet tally, overall pain control satisfaction 
(Yes/No question) 
o Demographics 

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o Age, male infertility diagnoses (i.e. presence of varicocele), prior surgical history, 
current medications, historical lab evaluation (FSH, LH, total testosterone, 
semen analyses, sperm DNA integrity tests such as tunel or SCSA assay, 
karyotype data, y-microdeletion status), pathology results of testis biopsy 
• 
Data safety 
o Data will be kept in REDCap, which is licensed by WCMC and is HIPAA compliant. 
Only study personnel will have access to the database. Hard or software copies 
of the database will not be allowed.  The database will only be accessed within 
the WCMC network utilizing WCMC tagged devices. Subject identifiers will be 
replaced by study identifiers as soon as data collection is complete. 
 
 
 

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