Clinical trial NCT02929589
Conditions: Pain Hernia
Sponsor: Mike O'Callaghan Military Hospital
Start date: 2018-07-05; Completion date: 2021-08-23
Enrollment: 18 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a prospective, randomized, double-blinded, and placebo-controlled trial comparing oxycodone/acetaminophen prescribed with or without ibuprofen for pain control following open unilateral inguinal hernia repair, with allowed exception of any currently prescribed opioid (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, transdermal fentanyl), which can be continued. The patients will not be allowed to continue any over-the-counter pain medications, such as ibuprofen, naproxen, or acetaminophen containing medications, that were not prescribed by the investigators during this study. Patients not receiving Ibuprofen will be given a placebo pill composed of corn starch. The placebo pill will be formulated into the same shape, size and color as the ibuprofen capsule. Neither the investigators nor the research subjects will know if the subject is receiving a placebo versus Ibuprofen. The subjects will complete pain level and medication diaries, and will be followed for 2 months after their surgery. The research aims to discover the appropriate amount of opioid medication to prescribe to patients undergoing an elective open inguinal hernia repair, and reduce the total opioid dose needed by utilizing ibuprofen in combination. The investigators expect that the subjects who take ibuprofen will use less oxycodone/acetaminophen, and have comparable or lower mean pain levels. This could contribute to reducing the surplus opioids prescribed by physicians after surgery, which can lead to opioid use disorders. This particular procedure is common in men, and the findings have the potential to decrease the symptoms and pain of Active Duty members and DoD beneficiaries who undergo an inguinal hernia repair, and are at risk for prescription drug abuse or dependence.

Detailed description:
Screening Visit:

Discuss the purpose of the study and the required completion of study-related questionnaires and their potential impact for active duty members. (research-driven) Obtain signed Informed Consent Document and HIPAA Authorization (research-driven).

Review the patient's past medical history in Armed Forces Health Longitudinal Technology Application (AHLTA) or ESSENTRIS to verify the inclusion/exclusion criteria. (research-driven) The investigators will record the subject's tobacco use history, alcohol use history, marijuana use history, other illicit drug use history, and previous non-prescription use of opioids. (standard of care) Obtain an overall pain score, from 0 to 100, with 100 being the worst pain imaginable. (research-driven) Obtain a localized pain score from 0 to 100, with 100 being the worst pain imaginable, which the patient attributes specifically to the hernia that is scheduled for surgical intervention. (research-driven) Instruct patients to discontinue use of any over-the-counter pain medications, such as ibuprofen, naproxen, or acetaminophen containing medications, that were not prescribed by the investigators during this study.

Subjects will have the following blood test drawn, which include (research-driven):

Fasting comprehensive metabolic panel (liver function, renal function, plasma glucose tests) via 1 venipuncture (5-10 milliliters, approximately 1-2 teaspoons of blood will be drawn) Subject's CMP results must be within 30 days of the day of surgery or it will need to be repeated.

Women of childbearing potential will have a serum pregnancy test (5-10 milliliters, approximately 1-2 teaspoons of blood) or urine pregnancy test (10 drops or less than 1 milliliter of urine) (research-driven). Visit 1 (may occur the same day as the screening visit or the same day as visit 2):

The standard of care local anesthesia used for this type of surgery is bupivacaine. The surgeon will be reminded via a note in the medical record. (standard of care) Subjects will be randomized by the MOFMC Pharmacy into one of two naturally stratified groups (e.g., opioid naive patients and non-opioid naive patients), with further randomization into an opioid + ibuprofen study group or an opioid + placebo study group The MOFMC Pharmacy staff will maintain a key that can be used to un-blind the randomization scheme if needed for an emergent patient care issue. Study ID numbers will be used to maintain blinding and confidentiality. (research-driven)

Opioid naive patients (used an opioid for less than 14 days in the past 6 months, and no history of opioid use disorder at any time) will be randomized into one of two groups:

Group A: Subjects will be prescribed ibuprofen 800 milligrams by mouth every 8 hours as needed for pain for 5 days, and 1 to 2 tablets of oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain for 5 days.

Group B: Subjects will be prescribed 800 milligrams of a placebo pill (containing corn starch) to be taken by mouth every 8 hours as needed for pain and 1 to 2 tablets of oxycodone/acetaminophen 5 milligrams 325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain for 5 days.

Non-Opioid naive patients (opioid use for more than 14 days in the past 6 months, or history of opioid use disorder) will be randomized into one of two groups:

Group C: Subjects will be prescribed ibuprofen 800 milligrams by mouth every 8 hours as needed for pain for 5 days, in addition to their preferred opioid medication prescription.

Group D: Subjects will be prescribed or advised to continue to take only their preferred current oral opioid prescription (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, or transdermal fentanyl).

Subjects will complete the Beck Depression Inventory-II or the Patient Health Questionnaire (PHQ-9) depression screen, and it will be reviewed on the same day of completion. (research-driven) Subjects will complete the Pre-Operative Activities Assessment Scale (AAS), and it will be reviewed on the same day of completion. (research-driven) Subjects will complete the Opioid Risk Tool (ORT) , and it will be reviewed on the same day of completion. (research-driven) Subjects will be asked "How likely do you think it is that you will develop an addiction problem from pain medication you take after surgery?" and chose from 1 of 4 answers: 1: "not at all"; 2: "unlikely"; 3: "somewhat likely"; or 4: "very likely". (research-driven) Subjects will be asked "On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average level of pain at rest in the past 24 hours?" (research-driven) Subjects will be asked "On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest level of pain when at rest in the past 24 hours? (research-driven) Subjects will be asked "On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest level of pain when at rest in the past 24 hours? (research-driven) Subjects will be given a Medication and Pain Level Diary and will be instructed to complete it every day for 14 days beginning after their surgery. The investigators will record information from the subjects' surgery, for example: the start and end times of surgery and anesthesia, how long the surgery lasted, how difficult the surgery was, were the ilioinguinal, genitofemoral, or iliohypogastric nerves identified and were they protected, injured, or transected, and which opioids the anesthesiologist gives at any point during the case after incision. (research-driven) The preoperative instructions will include standardized verbal and written instructions: "After your surgery, it is expected that the patient will experience a certain amount of pain for a short period of time. The patient will be prescribed pain medication that you should take only when you are in pain. If the patient is no longer experiencing pain, the patient should stop taking the medication. If the patient does not require all of the pain medication that was prescribed, the patient should record the amount of medication that was unused and then properly dispose of the remainder." (standard of care)

Visit 2 (day of surgery-prior to surgery):

Subjects will receive prescriptions for medications according to their randomization group. These prescriptions will be filled at the MOFMC pharmacy, which will perform the subjects' randomization assignments. The ibuprofen and placebo capsules will be delivered to the MOFMC Pharmacy after being compounded by Solutions Specialty Pharmacy. (research-driven) Subjects will complete the Pre-Operative AAS (approximately 5 minutes to complete), and it will be reviewed on the same day of completion. (research-driven) Research staff will record the start and end times of the surgery, record the amounts of standard of care pain medications used during their hospital stay, document any standard of care pain assessments that were performed, and document the anesthesia the subject received. (research-driven) Subjects will be reminded in the Post Anesthesia Care Unit (PACU) to complete their Medication and Pain Level Diary and reminded to complete it every day for the 60 days beginning after they are discharged from the hospital. (research-driven)

Visit 3 (Post-Op day 0 Contact (at time of discharge from post-anesthesia care unit)):

Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-driven):

On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is the average level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the lowest level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the highest level of pain when at rest in the past 24 hours? What pain medications are the patient taking including the strength (in milligrams), and how many total doses have you taken since your surgery? Time of last opioid medication taken? Relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete Subjects will be reminded to complete their Medication and Pain Level Diary. (research-driven)

Visits 4-8 (Post-op Day 1 through Day 5 Contact (each visit every 24 hours plus or minus 4 hours visit window):

Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-driven):

On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is the average level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the lowest level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the highest level of pain since when at rest in the past 24 hours? What pain medications have been taken, including the strength (in milligrams), and how many total doses have been taken since the last study visit? Time of last opioid medication taken? Relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven) Subjects will be reminded to complete their Medication and Pain Level Diary. (research-driven)

Visit 9 (Post-Op day 14 Contact (plus or minus 2 day visit window)):

Subjects will be contacted by research team in person or via telephone at their Post-Operative Follow Up Visit and asked the following questions in this order (in-person) (research-driven):

On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is the average level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest level of pain since your when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest level of pain since your when at rest in the past 24 hours? What pain medications are being taken including the strength (in milligrams), and how many total doses have been taken since the last study visit? Time of last opioid medication taken? Relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven).

Subjects will return their Medication and Pain Level Diary and be issued a new one for the remainder of the study. (research-driven) Subjects will be reminded of the two remaining contacts. (research-driven)

Visit 10 (Post-Op day 30 Contact (plus or minus 5 day visit window)):

Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-driven):

On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is the average level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the lowest level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the highest level of pain when at rest in the past 24 hours? What pain medications are being taken including the strength (in milligrams), and how many total doses have been taken since your last study visit? Time of last opioid medication taken? Relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven).

Subjects will be reminded to complete their Medication and Pain Level Diary. (research-driven)

Visit 11 (Post-Op day 60 Contact (plus or minus 5 day visit window)):

Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-driven):

On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average level of pain when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the lowest level of pain since your when at rest in the past 24 hours? On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was the highest level of pain when at rest in the past 24 hours? What pain medications are being taken including the strength (in milligrams), and how many total doses have been taken since the last study visit? Time of last opioid medication taken? Relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete Was there a diagnosis of post-operative neuralgia at any point following your surgery? Was there a diagnosis of an inguinal hernia recurrence at any point following your surgery? Was there a diagnosis of a surgical site infection at any point following your surgery? Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven).

The Medication and Pain Level Diary will not be collected from the patient. (research-driven)

Arms: arm 1: Group A: Subjects will be prescribed ibuprofen 800 milligrams by mouth every 8 hours as needed for pain for 5 days, and 1 to 2 tablets of oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain for 5 days.

. arm 2: Group C: Subjects will be prescribed ibuprofen 800 milligrams by mouth every 8 hours as needed for pain for 5 days, in addition to their preferred opioid medication prescription. arm 3: Group B:Subjects will be prescribed 800 milligrams of a placebo pill (containing corn starch) to be taken by mouth every 8 hours as needed for pain and 1 to 2 tablets of oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain for 5 days. arm 4: Group D: Subjects will be prescribed or advised to continue to take only their preferred current oral opioid prescription (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, or transdermal fentanyl).
Interventions: intervention 1: Ibuprofen intervention 2: Opioid Medication intervention 3: Placebo intervention 4: Ibuprofen + Opioid medication
Intervention descriptions: intervention 1: ibuprofen 800 milligrams by mouth every 8 hours as needed for pain for 5 days intervention 2: 1 to 2 tablets of oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain for 5 days intervention 3: 800 milligrams of a placebo pill (containing corn starch) to be taken by mouth every 8 hours as needed for pain intervention 4: ibuprofen 800 milligrams by mouth every 8 hours as needed for pain for 5 days. 1 to 2 tablets of oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain for 5 days

Protocol documents:
Prot_SAP_001.pdf: 
Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
Study 
 
NCT02929589 
 
Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal 
Herniorrhaphy 
 
Doc Date: 7/27/20 
 


Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
Study 
PROTOCOL FOR CLINICAL INVESTIGATION – NON-EXEMPT HUMAN 
(Wilford Hall Ambulatory Surgical Center – WHASC) 
 
PROTOCOL SUMMARY 
1.  Title: 
Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-
Controlled, Double-Blind, Randomized Controlled Trial 
FWH20160095H                  
 
 
2.0.  Principal Investigator (PI): 
 
                              MOFMC PI: 
 
        MOFMC Co-PI: 
Name 
 
William H. Scott, Jr., DO 
 
Rank/Corps or Civilian Rating 
 
Maj 
 
Date of IRB Approved CITI Training & 
Date of Good Clinical Practice Training  
10/26/13 
 
Branch of Service 
USAF 
 
AD Mil/DoD Civilian/Ctr/Non-DoD Civ 
AD Mil 
 
Department & Base 
 
General Surgery, Nellis Air Force Base 
 
Phone & Pager #  
(702) 822-0377 
 
E-Mail Address & 
AKO/DKO E-Mail Address 
william.scott.37@us.af.mil 
 
 
3.0. Research Plan:  
3.1. Purpose:  The purpose of this study is to investigate the decrease in post-operative pain and post-operative opioid usage 
(oxycodone/acetaminophen), in morphine equivalent units (MEUs), following open unilateral inguinal hernia repair, between 
subjects taking supplemental ibuprofen to subjects not taking ibuprofen. Oxycodone/acetaminophen are commonly prescribed 
medications for pain control following surgical procedures. The study will investigate both opioid naïve and non-opioid naïve 
patients, to assess for differences in opioid medication requirements, pain relief and activity levels between these groups. 
 
3.2. Hypotheses, Research Questions, or Objectives: To quantify the average MEUs necessary to provide adequate pain relief 
following an open unilateral inguinal hernia repair in adults, in order to reduce the amount of surplus opioids prescribed. To 
determine if the combination of ibuprofen with oxycodone (an opioid) and acetaminophen can decrease the total MEUs consumed 
in the post-operative period.  The secondary objectives include assessing the validity of the previous findings that depressive 
symptoms and self-perceived risk for opioid addiction predict prolonged use of opioid medications following surgery.  The secondary 
objective will be assessed using a depression screening questionnaire, and an opioid addiction risk questionnaire and single 
question.  The physical activity of the subjects will also be assessed via serial questionnaires to determine if the patients taking 
ibuprofen have a quicker return to baseline physical activity versus the placebo-controlled groups (no ibuprofen). 
 
4.  Brief Summary of the study: This is a prospective, randomized, double-blinded, and placebo-controlled trial comparing 
oxycodone/acetaminophen prescribed with or without ibuprofen for pain control following open unilateral inguinal hernia repair, 
with allowed exception of any currently prescribed opioid (codeine, hydrocodone, hydromorphone, morphine, methadone, 
oxymorphone, transdermal fentanyl), which can be continued. The patients will not be allowed to continue any over-the-counter 
pain medications, such as ibuprofen, naproxen, or acetaminophen containing medications, that were not prescribed by the 
investigators during this study.  Patients not receiving Ibuprofen will be given a placebo pill composed of corn starch.  The placebo 
pill will be formulated into the same shape, size and color as the ibuprofen capsule.  Neither the investigators nor the research 
subjects will know if the subject is receiving a placebo versus Ibuprofen. The subjects will complete pain level and medication diaries, 
and will be followed for 2 months after their surgery. The research aims to discover the appropriate amount of opioid medication to 
prescribe to patients undergoing an elective open inguinal hernia repair, and reduce the total opioid dose needed by utilizing 
ibuprofen in combination. We expect that the subjects who take ibuprofen will use less oxycodone/acetaminophen, and have 
comparable or lower mean pain levels. This could contribute to reducing the surplus opioids prescribed by physicians after surgery, 
which can lead to opioid use disorders. This particular procedure is common in men, and the findings have the potential to decrease 
the symptoms and pain of Active Duty members and DoD beneficiaries who undergo an inguinal hernia repair, and are at risk for 
prescription drug abuse or dependence.  
 
5. Subjects: Active Duty members and DoD beneficiaries age 18 or older will be recruited at the MOFMC. No special populations 
(e.g., pregnant women, children, military basic trainees, prisoners, detainees) will be recruited. 
 
6. Inclusion/exclusion criteria:  
Inclusion: 
• Active Duty members and DoD beneficiary patient 18 years or older 


Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
Study 
• Elective, open unilateral inguinal herniorrhaphy using Lichtenstein (tension free with mesh) hernia repair technique 
Agree to take only the prescribed oral analgesic medication (oxycodone/acetaminophen), plus or minus ibuprofen, for the initial 
fourteen-day post-operative period, with allowed exception of any currently prescribed opioid (codeine, hydrocodone, 
hydromorphone, morphine, methadone, oxymorphone, transdermal fentanyl), which can be continued.Agree to honestly complete 
a depression screening questionnaire, illicit drug use personal history and questionnaire, and physical activity assessment 
questionnaire, with the knowledge that if the patient is an active duty member, this information could result in a referral to medical 
or command authorities for potential Uniform Code of Military Justice (UCMJ) violations or concerns for subject health and fitness 
for duty. 
Exclusion: 
• Subjects who are pregnant or nursing. 
• Patients who refuse to complete the illicit drug use, physical activity, and depression questionnaires. 
• Strangulated, incarcerated, or otherwise emergent, urgent, and non-elective inguinal herniorrhaphy. 
• Those patients who are allergic to, refuse to take, or are otherwise unable to take oxycodone, ibuprofen, or acetaminophen 
medication orally for post-operative pain management. 
• Patients on pain contracts, or under the care of a pain medicine specialist for management of chronic pain at the time of surgery. 
• Subjects with serum creatinine level > 1.3 mg/dL as measured at the baseline study visit. 
• Subjects with serum aspartate transaminase (AST) greater than 3 times the upper limit of normal (level >102 U/L) 
• Subjects with serum alanine transaminase (ALT) greater than 3 times the upper limit of normal (level > 165 U/L) 
• Subjects who do not speak, read, and write fluently in English. 
• Subjects with a history of cirrhosis. 
• Subjects enrolled in another clinical trial during the same period as their involvement as this study. 
• Subjects, who in the investigator’s opinion, will be unable to complete a pain diary or follow-up visits, or otherwise not comply 
with the study protocol. 
 
7.  Number of Subjects:  TOTAL NUMBER OF SUBJECTS (nation-wide/study-wide):  185 
 
8.  Use of an Investigational New Drug: N/A 
9.  Use of an Investigational Device:  N/A 
10. Use of a Placebo: Yes. The placebo is a capsule filled with corn starch.  The placebo will be formulated by Solutions Specialty 
Pharmacy in Las Vegas, Nevada, which will be responsible for the compounding of ibuprofen capsules and the manufacture of the 
placebo capsules. The placebo capsules will be filled with corn starch. The placebo and ibuprofen capsules will appear identical, so 
the subjects, research staff, and investigators remain blinded to the study assignments.  The Solutions Specialty Pharmacy will label 
bottles of the ibuprofen and the placebo prior to delivery to the MOFMC Pharmacy.  The MOFMC Pharmacy will be responsible for 
randomizing the patients using a random number generator, in order to maintain blinding of the patients and the investigators.  The 
MOFMC Pharmacy will be able to un-blind the randomization if needed for an emergency medical care.  The MOFMC Pharmacy will 
be responsible for dispensing the ibuprofen capsules, placebo capsules, and oxycodone/acetaminophen tablets.  The investigators 
and patients will be blinded to the randomization groups. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROTOCOL FOR CLINICAL INVESTIGATION – NON-EXEMPT HUMAN 
(Wilford Hall Ambulatory Surgical Center – WHASC) 
1.  Title: 


Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
Study 
Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-
Controlled, Double-Blind, Randomized Controlled Trial 
FWH#:                  
 
2.0. Principal Investigator (PI): 
 
                              MOFMC PI: 
 
        MOFMC Co-PI: 
Name 
 
William H. Scott, Jr., DO 
 
Rank/Corps or Civilian Rating 
 
Maj 
 
Date of IRB Approved CITI Training & 
Date of Good Clinical Practice Training  
10/26/13 
 
Branch of Service 
USAF 
 
AD Mil/DoD Civilian/Ctr/Non-DoD Civ 
AD Mil 
 
Department & Base 
 
General Surgery, Nellis Air Force Base 
 
Phone & Pager #  
(702) 822-0377 
 
E-Mail Address & 
AKO/DKO E-Mail Address 
william.scott.37@us.af.mil 
 
 
2.1. Associate Investigators (AI):   
Name 
AD/DoD 
Civ/Ctr/ 
Non-DoD Civ 
Rank/Corps or Civilian 
Rating/Title 
Date of CITI Training 
Phone & Pager # 
Charles H. Chesnut III, DO 
AD 
Maj, USAF, Physician 
07/21/16 
Phone: (740) 360-9707 
Nicolas Danscuk, DO 
 
AD 
CAPT, USAF, Resident 
Physician 
07/19/16 
Phone: (415) 235-1806 
Pager: (702) 264-1501 
Ashley Martin, DO 
AD 
CAPT, USAF, Resident 
Physician 
07/22/16 
Phone: (617) 515-9321 
Pager: (702) 264-1476 
 
2.2. Research Assistants (RA) & Coordinators (RC):   
Name 
AD/DoD 
Civ/Ctr/ 
Non-DoD Civ 
Rank/Corps or Civilian Rating/Title 
Date of CITI 
Training 
Phone & Pager #  
Jill Clark, MBA/HCM 
Ctr 
Senior Research Associate/Clinical 
Research Manager 
03/20/14 
(702) 653-3298 
Jennie Moss, RN, M.S. 
CTR 
Senior Research Associate 
09/01/15 
(702) 653-2113 
Tracy Bogdanovich, CCRC 
Ctr 
Clinical Research Coordinator 
04/03/14 
(702) 653-2088 
Lisa Stammers, RN, BSN 
DoD Civ 
DME Nurse 
06/17/14 
(702) 653-3239 
Daniel Shaffer, BSBA 
Ctr 
Clinical Research Coordinator 
06/29/15 
(702) 653-2067 
Heather Rider, B.S. 
Ctr 
Clinical Research Coordinator 
07/21/15 
(702) 653-2521 
 
2.3. The research relevance of this protocol focuses on: 
[] Diagnosis 
[X] Treatment 
[] Medical Utilization/Managed Care 
[] Prevention 
[] Medical Readiness 
 
[] Other 
 
2.4. Location(s):   
a. Collaborating Facilities: N/A 
 
b. Air Force Sites seeking Regional IRB: MOFMC, Jill Clark, (702) 653-3298 
 
c. List study sponsors: N/A 
 
3.  Research Plan: 
3.1. Purpose: The purpose of this study is to investigate the decrease in post-operative pain and post-operative opioid usage 
(oxycodone/acetaminophen), in morphine equivalent units (MEUs), following open unilateral inguinal hernia repair, between 
subjects taking supplemental ibuprofen to subjects not taking ibuprofen. Oxycodone/acetaminophen are commonly prescribed 
medications for pain control following surgical procedures. The study will investigate both opioid naïve and non-opioid naïve 
patients, to assess for differences in opioid medication requirements, pain relief and activity levels between these groups 
 
3.2. Hypotheses, Research Questions, or Objectives: To quantify the average MEUs necessary to provide adequate pain relief 
following an elective, open unilateral inguinal hernia repair in adults, in order to reduce the amount of surplus opioids prescribed. To 
determine if the combination of ibuprofen with oxycodone (an opioid) and acetaminophen can decrease the total MEUs consumed 
in the post-operative period.  The secondary objectives include assessing the validity of the previous findings that depressive 
symptoms and self-perceived risk for opioid addiction predict prolonged use of opioid medications following surgery.  The secondary 


Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
Study 
objective will be assessed using a depression screening questionnaire, and an opioid addiction risk questionnaire and single 
question.  The physical activity of the subjects will also be assessed via serial questionnaires to determine if the patients with 
ibuprofen have a quicker return to baseline physical activity. 
   
3.3.  Significance: Prescription opioid use and opioid use disorders among Americans have steadily increased since 1999.(1)(2) The 
prevalence of prescription opioid use disorders reached 0.9% in 2013, and the mortality rate was 7.8 per 100,000 in 2013 among 
adults age 18 to64.(2)  Over 90,000 emergency department visits for prescription drug overdoses occurred in 2010, with the 
resultant total hospital costs reaching $1.2 billion.(3)  The multifaceted approach to reducing the harms from prescription opioid use 
disorders includes prescription drug monitoring programs, widely available naloxone, and primary prevention through education.(1)  
However, changing prescribing habits is an important piece of the puzzle that must not be overlooked.(1) Few studies have been 
done looking at opioid usage within certain post-operative groups.(4)(5)(6)  In their big data retrospective review, Wunsch et al. 
found that the average prescription for MEU medication filled in the 7 days after an inguinal hernia repair had increased to 229 
milligrams in 2012 from 212 milligrams in 2004 (p<0.001).(7)  We also know that combining an intra-operative regional field block 
with post-operative acetaminophen, a non-steroidal anti-inflammatory drug, and an opioid is the recommended treatment for post-
operative pain following inguinal hernia repair in adults.(8)  This research aims to help guide physicians as to the appropriate dose of 
opioid medications that should provide a patient with adequate pain relief following a unilateral open inguinal hernia repair.  We 
hope to decrease unnecessary opioid prescriptions, and therefore decrease overdoses and opioid use disorders, through the 
knowledge gained in this research. 
 
3.4. Military Relevance: This research will provide a reference for military surgeons to adequately control post-operative pain 
following an inguinal hernia repair, while reducing the prescription of surplus opioids that may contribute to opioid use disorders. 
Opioid overdoses and use disorders are significant burdens on the mental, physical, and financial health of military members. The 
inguinal hernia repair is one of the most common general surgical procedures performed, with a higher incidence in men. The 
findings from this research have the ability to change prescribing habits for a common surgical procedure performed for military 
members. The findings may also translate well to other surgical procedures. 
  
3.5.  Background and Review of Literature: Prescription opioid use and opioid use disorders among Americans have steadily 
increased since 1999, causing more overdoses, and increasing health care costs.(1)(2)(3) A multifaceted approach to reducing the 
harms from prescription opioid use disorders includes prescription drug monitoring programs, widely available naloxone, and 
primary prevention through education.(1)  However, changing prescribed habits is an important piece of the puzzle that must not be 
overlooked.(1) Few studies have been done looking at opioid usage within certain post-operative groups.(4)(5)(6)(9)  However, 
Litkowski et al. looked at oxycodone and ibuprofen for post-operative pain control after oral surgery, and noted that patients had 
significantly less total pain and larger sum of pain intensity differences at 3 hours compared to oxycodone with acetaminophen and 
hydrocodone with acetaminophen.(10) Van Dyke et al showed that oxycodone with ibuprofen was more effective at controlling 
post-surgical dental pain than oxycodone alone.(11)  While Johnson et al. found that the combination of oxycodone with 
acetaminophen had better analgesic effect than 400 milligrams of ibuprofen alone(12), Singla et al. found that 400 milligrams of 
ibuprofen resulted in superior pain relief for women after abdominal surgery when compared to 5 milligrams of oxycodone.(10) 
Hydrocodone with ibuprofen has also been found to have better post-operative pain reduction than oxycodone with 
acetaminophen.(13)  Stambaugh and Drew found that the addition of 600 milligrams of ibuprofen to the pain control regimen of 
patients with metastatic cancer to the bone resulted in decreased use of oxycodone with acetaminophen compared to placebo.(14)  
 
The current standard of care for post-operative pain control, following inguinal hernia repair surgery, by the investigators is 5 
milligrams of oxycodone with 325 milligrams of acetaminophen, taken by mouth every 4 hours as needed for pain relief. The current 
standard of care for ibuprofen prescription for post-operative pain utilized by the investigators is 800 milligrams by mouth every 8 
hours. Ibuprofen was chosen because it has non-steroidal anti-inflammatory properties, but has the lowest side effect profile of this 
class of medications. (15) (16)  
 
The measurement of pain following surgery is another topic of the research study, with many options available to researchers. These 
options include visual analog scales (VAS), like the Surgical Pain Scales, numerical rating scales (NRS), verbal rating scales (VRS), or 
verbal numerical rating scales (VNRS).(17)(18)  The NRS and VNRS have consistently been shown to be more preferred by patients, 
with better compliance, and with good recall correlation of the pain experienced of at least one week. (17) (19)  
 
Many factors can potentially predict prolonged opioid use after an elective surgery, and some have been researched in studies of 
inguinal hernia surgery patients. Physicians are aware that certain patients are predisposed to using more opioid medication 
following surgery, with risk factors such as previous or current nicotine use or substance abuse.(20) Medical co-morbidities may also 
predispose persons to differing outcomes and medication use after surgery, and the Centers for Medicare and Medicaid Services’ 
Hierarchical Condition Category Risk Adjustment Model is the superior tool in predicting post-operative outcomes.(21) A quick 
depression symptom screen known as PHQ-9 may help identify the patient population at higher risk for prolonged opioid use or 
opioid dependence after surgery.(22)  There have been many scales and scores developed to assess functional activity following 
surgery, such as the  Activities Assessment Scale (AAS). (23) (24) (25) The AAS has been validated in men who underwent inguinal 


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hernia repair, as well as women who underwent pelvic reconstructive surgery.(25)(26) These scales describe the level of activity that 
the patient has after surgery, and will help the researchers determine the level of physical impairment each patient is experiencing 
before and after surgery. A short Opioid Risk tool has also been found to identify patients at risk for displaying “aberrant behaviors” 
when they are prescribed opioids.(27)(28)  This tool can help identify patients at risk for prolonged opioid use after surgery, and this 
will help the researchers determine if this tool is useful in this study population as well. We also know that patients taking opioid 
medication prior to an elective surgery score higher on the Beck Depression Inventory, Pittsburgh Sleep Quality Index, Screener and 
Opioid Assessment for Patients with Pain-Revised score, lower anxiety sensitivity, self-perceived risk of addiction, and have higher 
baseline pain at the surgical site and at other body sites.(29)(30)(31)(32)  In their big data retrospective review, Wunsch et al. found 
that the average prescription for morphine equivalent medication filled in the 7 days after an inguinal hernia repair had increased to 
229 milligrams in 2012.(7)  We also know that combining an intra-operative regional field block with post-operative acetaminophen, 
a non-steroidal anti-inflammatory drug, and an opioid is the recommended treatment for post-operative pain following inguinal 
hernia repair in adults.(8)  In fact, if patients are not given a prescription for an opioid following their ambulatory surgery, they are 
significantly less likely to become chronic opioid users.(33) Yet, there is no current recommendation to answer the question, “how 
much should I prescribe my patient after surgery?”  Physicians are in danger of prescribing too few opioids, and causing their 
patients unnecessary pain, or prescribing too many opioids and contributing to the opioid use disorder epidemic. Given the more 
than $1.2 billion spent on hospital costs for inpatient prescription drug overdoses in 2010, clearly a systemic change is needed. (3) 
This research aims to provide physicians with a framework for the prescribing habits.  
 
3.5.1. Bibliography:  
1.  
Compton WM, Boyle M, Wargo E. Prescription opioid abuse: Problems and responses. Prev Med (Baltim). Elsevier B.V.; 2015 
Nov;80:5–9.  
2.  
Han B, Compton WM, Jones CM, Cai R. Nonmedical Prescription Opioid Use and Use Disorders Among Adults Aged 18 
Through 64 Years in the United States, 2003-2013. JAMA. 2015 Oct 13;314(14):1468–78.  
3.  
Yokell MA, Delgado MK, Zaller ND, Wang NE, McGowan SK, Green TC. Presentation of prescription and nonprescription 
opioid overdoses to US emergency departments. JAMA Intern Med. 2014 Dec 1;174(12):2034–7.  
4.  
Rafiq S, Steinbrüchel DA, Wanscher MJ, Andersen LW, Navne A, Lilleoer NB, et al. Multimodal analgesia versus traditional 
opiate based analgesia after cardiac surgery, a randomized controlled trial. J Cardiothorac Surg. 2014;9:52.  
5.  
Derry S, Derry CJ, Moore RA. Single dose oral ibuprofen plus oxycodone for acute postoperative pain in adults. Moore RA, 
editor. Cochrane database Syst Rev. Chichester, UK: John Wiley & Sons, Ltd; 2013 Jun 26;(6):CD010289.  
6.  
Au AHY, Choi SW, Cheung CW, Leung YY. The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-
Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis. Staffieri F, editor. PLoS One. 2015 Jun 
8;10(6):e0127611.  
7.  
Wunsch H, Wijeysundera DN, Passarella MA, Neuman MD. Opioids Prescribed After Low-Risk Surgical Procedures in the 
United States, 2004-2012. JAMA. 2016 Apr 19;315(15):1654.  
8.  
Joshi GP, Rawal N, Kehlet H, PROSPECT collaboration, Bonnet F, Camu F, et al. Evidence-based management of postoperative 
pain in adults undergoing open inguinal hernia surgery. Br J Surg. 2012 Feb;99(2):168–85.  
9.  
Alfano G, Grieco M, Forino A, Meglio G, Pace MC, Iannotti M. Analgesia with paracetamol/tramadol vs. paracetamol/codeine 
in one day-surgery: a randomized open study. Eur Rev Med Pharmacol Sci. 2011 Feb;15(2):205–10.  
10.  
Singla N, Pong A, Newman K, MD-10 Study Group. Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of pain 
after abdominal or pelvic surgery in women: a randomized, double-blind, placebo- and active-controlled parallel-group 
study. Clin Ther. 2005 Jan;27(1):45–57.  
11.  
Van Dyke T, Litkowski LJ, Kiersch TA, Zarringhalam NM, Zheng H, Newman K. Combination oxycodone 5 mg/ibuprofen 400 
mg for the treatment of postoperative pain: a double-blind, placebo- and active-controlled parallel-group study. Clin Ther. 
2004 Dec;26(12):2003–14.  
12.  
Johnson GH, Van Wagoner JD, Brown J, Cooper SA. Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo 
for relief of postoperative pain. Clin Ther. 1997;19(3):507–19.  
13.  
Palangio M, Morris E, Doyle RT, Dornseif BE, Valente TJ. Combination hydrocodone and ibuprofen versus combination 
oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain. Clin Ther. 2002 Jan;24(1):87–
99.  
14.  
Stambaugh JE, Drew J. The combination of ibuprofen and oxycodone/acetaminophen in the management of chronic cancer 
pain. Clin Pharmacol Ther. 1988 Dec;44(6):665–9.  
15.  
Henry D, Lim LL, Garcia Rodriguez LA, Perez Gutthann S, Carson JL, Griffin M, et al. Variability in risk of gastrointestinal 
complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ. 1996 Jun 
22;312(7046):1563–6.  
16.  
Griffin MR, Piper JM, Daugherty JR, Snowden M, Ray WA. Nonsteroidal anti-inflammatory drug use and increased risk for 
peptic ulcer disease in elderly persons. Ann Intern Med. 1991 Feb 15;114(4):257–63.  
17.  
Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, et al. Studies comparing Numerical Rating Scales, 
Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J 
Pain Symptom Manage. Elsevier Inc; 2011 Jun;41(6):1073–93.  
18.  
McCarthy M, Chang C-H, Pickard AS, Giobbie-Hurder A, Price DD, Jonasson O, et al. Visual analog scales for assessing surgical 


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pain. J Am Coll Surg. 2005 Aug;201(2):245–52.  
19.  
Singer AJ, Kowalska A, Thode HC. Ability of patients to accurately recall the severity of acute painful events. Acad Emerg 
Med. 2001 Mar;8(3):292–5.  
20.  
Hooten WM, St Sauver JL, McGree ME, Jacobson DJ, Warner DO. Incidence and Risk Factors for Progression From Short-term 
to Episodic or Long-term Opioid Prescribing: A Population-Based Study. Mayo Clin Proc. 2015 Jul;90(7):850–6.  
21.  
Mehta HB, Dimou F, Adhikari D, Tamirisa NP, Sieloff E, Williams TP, et al. Comparison of Comorbidity Scores in Predicting 
Surgical Outcomes. Med Care. 2016 Feb;54(2):180–7.  
22.  
Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: Validity of a brief depression severity measure. J Gen Intern Med. 
2001;16(9):606–13.  
23.  
Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 
12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381–95.  
24.  
Jensen KK, Kjaer M, Jorgensen LN. Isometric abdominal wall muscle strength assessment in individuals with incisional hernia: 
a prospective reliability study. Hernia. Springer Paris; 2016 May 12;  
25.  
McCarthy M, Jonasson O, Chang CH, Pickard AS, Giobbie-Hurder A, Gibbs J, et al. Assessment of patient functional status 
after surgery. J Am Coll Surg. 2005;201(2):171–8.  
26.  
Barber MD, Kenton K, Janz NK, Hsu Y, Dyer KY, Greer WJ, et al. Validation of the activities assessment scale in women 
undergoing pelvic reconstructive surgery. Female Pelvic Med Reconstr Surg. 2013;18(4):205–10.  
27.  
Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk 
Tool. Pain Med. 2005;6(6):432–42.  
28.  
Passik SD, Kirsh KL, Casper D. Addiction-Related Assessment Tools and Pain Management: Instruments for Screening, 
Treatment Planning, and Monitoring Compliance. Pain Med. 2008 Jul;9(SUPPL. 2):S145–66.  
29.  
Hah JM, Sharifzadeh Y, Wang BM, Gillespie MJ, Goodman SB, Mackey SC, et al. Factors Associated with Opioid Use in a 
Cohort of Patients Presenting for Surgery. Pain Res Treat. Hindawi Publishing Corporation; 2015;2015:1–8.  
30.  
Hah JM, Mackey S, Barelka PL, Wang CKM, Wang BM, Gillespie MJ, et al. Self-loathing aspects of depression reduce 
postoperative opioid cessation rate. Pain Med. 2014 Jun 1;15(6):954–64.  
31.  
Carroll I, Barelka P, Wang CKM, Wang BM, Gillespie MJ, McCue R, et al. A Pilot Cohort Study of the Determinants of 
Longitudinal Opioid Use After Surgery. Anesth Analg. 2012 Jun;115(3):1.  
32.  
Carroll IR, Hah JM, Barelka PL, Wang CKM, Wang BM, Gillespie MJ, et al. Pain Duration and Resolution following Surgery: An 
Inception Cohort Study. Pain Med. 2015 Dec;16(12):2386–96.  
33.  
Alam A, Gomes T, Zheng H, Mamdani MM, Juurlink DN, Bell CM. Long-term analgesic use after low-risk surgery: a 
retrospective cohort study. Arch Intern Med. 2012 Mar 12;172(5):425–30.  
34. 
Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, 
and biomedical sciences. Behavior Research Methods. 2007; 39 (2): 175-191. 
35. 
R Core Team (2014). R: A language and environment for statistical computing. R Foundation for Statistical 
Computing,Vienna, Austria. URL http://www.R-project.org/. 
36. 
Abdi H. Bonferroni and Šidák corrections for multiple comparisons. In N.J. Salkind (ed.). Encyclopedia of Measurement and 
Statistics. 2007; Thousand Oaks, CA: Sage. 
37.  
Huxtable CA, Roberts LJ, Somogyi AA, MacIntyre PE. Acute pain management in opioid-tolerant patients: a growing 
challenge. Anaesth Intensive Care. 2011;39(5):804-823. 
38.  
Shah S, Kapoor S, Durkin B. Analgesic management of acute pain in the opioid-tolerant patient. Curr Opin Anaesthesiol. 
2015;28(4):398-402. 
 
3.6. Research Design and Methods: Active Duty members and DoD beneficiaries age 18 or older who meet the inclusion criteria will 
be offered an opportunity to participate in the study at the MOFMC. The PI or AI will not recruit their own patients to prevent any 
misconception of coercion or undue influence.  The placebo will be formulated by Solutions Specialty Pharmacy in Las Vegas, 
Nevada, which will be responsible for the compounding of ibuprofen capsules and the manufacture of the placebo capsules. The 
placebo capsules will be filled with corn starch. The placebo and ibuprofen capsules will appear identical, so the subjects, research 
staff, and investigators remain blinded to the study assignments.  The Solutions Specialty Pharmacy will label bottles of the 
ibuprofen and the placebo prior to delivery to the MOFMC Pharmacy.  The MOFMC Pharmacy will be responsible for randomizing 
the patients, in order to maintain blinding of the patients and the investigators.  The MOFMC Pharmacy will be able to un-blind the 
randomization if needed for an emergency medical care.  The MOFMC will be responsible for dispensing the ibuprofen capsules, 
placebo capsules, and oxycodone/acetaminophen tablets.  The investigators, research staff, and patients will be blinded to the 
randomization groups. 
 
Opioid medication use is common in the United States for both chronic and acute pain.  Much research has been performed 
previously to investigate reasons for the prolonged use of opioid medications for acute pain following surgery.(29-33)  This research 
has shown that self-perceived opioid risk, as well as depression symptoms, are independently predictive of prolonged opioid use 
following surgery.  In order to correctly assess the effect of ibuprofen on the reduction of MEUs consumed following surgery, the 
confounding factors of opioid use, addiction risk, and depression need to be assessed and accounted for in each subject.  This 
improves the internal validity of the study.  If the known confounders are not accounted for a priori, then the study’s results and 


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conclusions are substantially weakened.  In addition, this study will confirm the validity of previous findings regarding prolonged 
post-operative opioid use based on depression symptoms and opioid addiction risk. 
 
The depression screen previously validated for predicting prolonged opioid use following surgery is the Beck Depression Inventory-II 
(BDI-II). (29)(30)  The PHQ-9 is another depression screen that can also be used to identify depressive symptoms.(22)  Our research 
protocol allows for either depression screen to be utilized, but the plan will be to use the BDI-II if grant funding is obtained to 
purchase the rights to the tool.  If funding cannot be obtained, then the open access PHQ-9 tool will be used. 
 
Given the special population of Active Duty members, the identification of any history of substance abuse can have severe 
consequences for the Active Duty personnel.  Likewise, the identification of any mental health issues can have severe consequences 
for an Active Duty member’s career.  These consequences must not be taken lightly by the research staff or investigators, and must 
be made clear to the prospective subjects at the time of screening and enrollment.  The Active Duty personnel approached to 
consent to this study will be given a thorough explanation of the study procedures, including the collection of mental health and 
substance abuse questionnaires.  The risk to the subject will be minimized by allowing subjects to refuse to participate in the study.  
Additionally, the subject’s will be informed that they don’t have to complete or answer any question that they do not want to.  At 
the top of each questionnaire, a sticker will be placed that clearly states that the subject is not required to answer any or all 
questions, without repercussion.  The informed consent process will include an explanation of potential consequences if the subject 
is identified as having a substance abuse history or current use of illicit drugs, or mental health illness.  These consequences include 
reporting the illicit drug use to the commanding officer, and reporting the mental health issues to the subject’s physician, and 
potentially to the mental health office. 
 
Opioid withdrawal can be a deadly condition, and requires attentive care by physicians to prevent.  Persons who present in acute 
pain following surgery are continued on their usual opioid medication, and started on a short-term higher dose medication as 
well.(37)(38)  For this study, we will enroll patients who are both opioid naïve and opioid dependent. We will follow the standard 
practice of continuing the subject’s usual dose of opioid medication, and add oxycodone/acetaminophen plus or minus ibuprofen or 
placebo.  By measuring the MEUs, we will convert all opioid medications into one measurement system that allows comparison of 
any opioid medication to any other opioid medication, using morphine as the currency of exchange. 
 
Screening Visit: 
• 
Discuss the purpose of the study and the required completion of study-related questionnaires and their potential impact for 
active duty members. (research-driven) 
• 
Obtain signed Informed Consent Document and HIPAA Authorization (research-driven). 
• 
Review the patient’s past medical history in Armed Forces Health Longitudinal Technology Application (AHLTA) or ESSENTRIS to 
verify the inclusion/exclusion criteria. (research-driven) 
• 
We will record information from the pre-operative visits, including name, date of birth, age, phone number, current email 
address, gender, race, ethnicity, social security number, surgical history, family history (first degree relative) of opioid use 
disorder, medical history, height (in inches), weight (in pounds), waist circumference (in inches) measurement, blood pressure, 
temperature, pulse, respiratory rate, allergies, and medications including whether subject is taking any statins, fibrate, niacin or 
bile acid binding agent, opioid usage over the last 6 months. The medication record will include all current prescription and over 
the counter medications, including the use, frequency, and dosage. (standard of care)  Specifically, the use of acetaminophen 
alone or in combination with other medications will be recorded.  A co-morbidity score will be calculated using the Centers for 
Medicare and Medicaid Services’ Hierarchical Condition Category Risk Adjustment Model. (research-driven) 
• 
We will record the subject’s tobacco use history, alcohol use history, marijuana use history, other illicit drug use history, and 
previous non-prescription use of opioids. (standard of care) 
• 
Obtain an overall pain score, from 0 to 100, with 100 being the worst pain imaginable. (research-driven) 
• 
Obtain a localized pain score from 0 to 100, with 100 being the worst pain imaginable, which the patient attributes specifically 
to the hernia that is scheduled for surgical intervention. (research-driven) 
• 
Instruct patients to discontinue use of any over-the-counter pain medications, such as ibuprofen, naproxen, or acetaminophen 
containing medications, that were not prescribed by the investigators during this study. 
• 
Subjects will have the following blood test drawn, which include (research-driven): 
o Fasting comprehensive metabolic panel (liver function, renal function, plasma glucose tests) via 1 venipuncture (5-10 
milliliters, approximately 1-2 teaspoons of blood will be drawn) 
*Subject’s CMP results must be within 30 days of the day of surgery or it will need to be repeated.  
o 
Women of childbearing potential will have a serum pregnancy test (5-10 milliliters, approximately 1-2 teaspoons of blood) 
or urine pregnancy test (10 drops or less than 1 milliliter of urine) (research-driven).  If needed, the additional 5-10 
milliliters for the serum pregnancy test would be gathered via the same venipuncture as the fasting comprehensive 
metabolic panel. (standard of care) 
 
Visit 1 (may occur the same day as the screening visit or the same day as visit 2): 


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• 
The standard of care local anesthesia used for this type of surgery is bupivacaine. The surgeon will be reminded via a note in the 
medical record. (standard of care) 
• 
Subjects will be randomized by the MOFMC Pharmacy into one of two naturally stratified groups (e.g., opioid naïve patients and 
non-opioid naïve patients), with further randomization into an opioid + ibuprofen study group or an opioid + placebo study 
group The research coordinator will notify the MOFMC Pharmacy if the subject is an opioid naïve patient, or a non-opioid naïve 
patient to assist with stratification. A random-number generator blocking will be used to ensure roughly equal sample sizes. The 
groups will also be stratified by the Beck Depression Inventory-II score completed on visit 1 (greater than 13, or 13 or less), and 
by the self-perceived risk of addiction question asked on visit 1 (score of 1 or 2, vs. 3 or 4). If the Beck Depression Inventory-II is 
unavailable, then the PHQ-9 score will be used, with a cutoff of 10 or greater vs 9 or less. Subjects, research staff, and research 
investigators will be blinded to the study group assignments (research-driven).  The MOFMC Pharmacy staff will maintain a key 
that can be used to un-blind the randomization scheme if needed for an emergent patient care issue. Study ID numbers will be 
used to maintain blinding and confidentiality. (research-driven) 
o 
Opioid naïve patients (used an opioid for less than 14 days in the past 6 months, and no history of opioid use 
disorder at any time) will be randomized into one of two groups: 
 
Group A: Subjects will be prescribed ibuprofen 800 milligrams by mouth every 8 hours as needed for pain 
for 5 days, and 1 to 2 tablets of oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by 
mouth every 4 hours as needed for pain for 5 days. Refills will be prescribed if needed through the period 
of 14 days. Subjects will be instructed to take ibuprofen preferentially if able, and only use the opioid 
medication as a “breakthrough medication”. The total 24 hour dose of acetaminophen from all 
prescription and over the counter medications must not exceed 4 grams.  There is a potential for liver 
injury if more than 4 grams of acetaminophen is consumed in one day.   
 
Group B: Subjects will be prescribed 800 milligrams of a placebo pill (containing corn starch) to be taken 
by mouth every 8 hours as needed for pain and 1 to 2 tablets of oxycodone/acetaminophen 5 
milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain for 5 days. Refills will be 
prescribed if needed through the period of 14 days. Subjects will be instructed to take the placebo pill 
preferentially if able, and only use the opioid medication as a “breakthrough medication.” The total 24 
hour dose of acetaminophen from all prescription and over the counter medications must not exceed 4 
grams.  There is a potential for liver injury if more than 4 grams of acetaminophen is consumed in one 
day. The placebo pill will appear identical to the ibuprofen capsules to maintain blinding.  The MOFMC 
pharmacy can let the patient, the investigator, or treating medical personnel know your randomization 
group if needed in an emergency. 
o 
Non-Opioid naïve patients (opioid use for more than 14 days in the past 6 months, or history of opioid use 
disorder) will be randomized into one of two groups: 
 
Group C: Subjects will be prescribed ibuprofen 800 milligrams by mouth every 8 hours as needed for pain 
for 5 days, in addition to their preferred opioid medication prescription.  The subject’s previously 
prescribed (“home”) oral opioid medication must be one of the following medications: codeine, 
hydrocodone, hydromorphone, morphine, methadone, oxymorphone, or transdermal fentanyl.  The 
doses of these home opioid medications will not be changed, but will be recorded throughout the study 
to allow for a statistical comparison to be made between groups. All opioid medications will be converted 
to MEUs to allow for comparison. If the subject is not currently taking an opioid medication, or requires 
more opioid medication in addition to their current opioid medication, then they will be prescribed 
oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for 
pain for 5 days. Subjects will be instructed to take ibuprofen preferentially if able, and only use the opioid 
medication as a “breakthrough medication”. Refills will be prescribed if needed through the period of 14 
days. The total 24 hour dose of acetaminophen from all prescription and over the counter medications 
must not exceed 4 grams.  There is a potential for liver injury if more than 4 grams of acetaminophen is 
consumed in one day. 
 
Group D: Subjects will be prescribed or advised to continue to take only their preferred current oral opioid 
prescription (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, or 
transdermal fentanyl). If they are not currently taking an opioid medication, or require more opioid 
medication in addition to their current opioid medication, then they will be prescribed 
oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for 
pain for 5 days. They will also be prescribed a placebo pill (containing corn starch) to be taken by mouth 
every 8 hours as needed for pain. Subjects will be instructed to take the placebo pill preferentially if able, 
and only use the opioid medication as a “breakthrough medication.” Refills will be prescribed if needed 
through the period of 14 days. The total 24 hour dose of acetaminophen from all prescription and over 
the counter medications must not exceed 4 grams.  There is a potential for liver injury if more than 4 
grams of acetaminophen is consumed in one day.  The placebo pill will appear identical to the ibuprofen 
capsules to maintain blinding.  The MOFMC pharmacy can let the patient, the investigator, or treating 
medical personnel know your randomization group if needed in an emergency. 


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• 
Subjects will complete the Beck Depression Inventory-II or the Patient Health Questionnaire (PHQ-9) depression screen, and it 
will be reviewed on the same day of completion.  (research-driven) 
• 
Subjects will complete the Pre-Operative Activities Assessment Scale (AAS), and it will be reviewed on the same day of 
completion. (research-driven) 
• 
Subjects will complete the Opioid Risk Tool (ORT) , and it will be reviewed on the same day of completion. (research-driven) 
• 
Subjects will be asked “How likely do you think it is that you will develop an addiction problem from pain medication you take 
after surgery?” and chose from 1 of 4 answers: 1: “not at all”; 2: “unlikely”; 3: “somewhat likely”; or 4: “very likely”. (research-
driven) 
• 
Subjects will be asked “On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average 
level of pain at rest in the past 24 hours?” (research-driven) 
• 
Subjects will be asked “On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest 
level of pain when at rest in the past 24 hours? (research-driven) 
• 
Subjects will be asked “On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your 
highest level of pain when at rest in the past 24 hours? (research-driven) 
• 
Subjects will be given a Medication and Pain Level Diary and will be instructed to complete it every day for 14 days beginning 
after their surgery. The subjects will be instructed to begin recording their average pain number, highest pain number, and 
lowest pain number beginning 24 hours post-surgical incision. The research coordinator will annotate this on the diary. They will 
also be instructed to record the total milligrams of each medication used in the previous 24 hours. We will issue them a new one 
at the 14-day visit to help them keep track but we will not collect it at the end of the study. (research-driven) 
• 
We will record information from the subjects’ surgery, for example: the start and end times of surgery and anesthesia, how long 
the surgery lasted, how difficult the surgery was, were the ilioinguinal, genitofemoral, or iliohypogastric nerves identified and 
were they protected, injured, or transected, and which opioids the anesthesiologist gives at any point during the case after 
incision. (research-driven) 
• 
The preoperative instructions will include standardized verbal and written instructions: “After your surgery, it is expected that 
you will experience a certain amount of pain for a short period of time. You will be prescribed pain medication that you should 
take only when you are in pain. If you are no longer experiencing pain, you should stop taking the medication. If you do not 
require all of the pain medication that was prescribed, you should record the amount of medication that was unused and then 
properly dispose of the remainder.” (standard of care) 
 
Visit 2 (day of surgery-prior to surgery): 
• 
Subjects will receive prescriptions for medications according to their randomization group. These prescriptions will be filled at 
the MOFMC pharmacy, which will perform the subjects’ randomization assignments.  The ibuprofen and placebo capsules will 
be delivered to the MOFMC Pharmacy after being compounded by Solutions Specialty Pharmacy. (research-driven) 
• 
Subjects will complete the Pre-Operative AAS (approximately 5 minutes to complete), and it will be reviewed on the same day of 
completion. (research-driven) 
• 
Research staff will record the start and end times of the surgery, record the amounts of standard of care pain medications used 
during their hospital stay, document any standard of care pain assessments that were performed, and document the anesthesia 
the subject received. (research-driven) 
• 
Subjects will be reminded in the Post Anesthesia Care Unit (PACU) to complete their Medication and Pain Level Diary and 
reminded to complete it every day for the 60 days beginning after they are discharged from the hospital. (research-driven) 
 
Visit 3 (Post-Op day 0 Contact (at time of discharge from post-anesthesia care unit)): 
• 
Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-
driven): 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average level of pain when 
at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest level of pain when 
at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest level of pain 
when at rest in the past 24 hours?  
o 
What pain medications are you taking including the strength (in milligrams), and how many total doses have you taken 
since your surgery? Time of last opioid medication taken? 
o 
My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• 
Subjects will be reminded to complete their Medication and Pain Level Diary. (research-driven) 
 
Visits 4-8 (Post-op Day 1 through Day 5 Contact (each visit every 24 hours plus or minus 4 hours visit window): 
• 
Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-
driven): 


Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
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o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average level of pain when 
at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest level of pain since 
your when at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest level of pain since 
your when at rest in the past 24 hours? 
o 
What pain medications are you taking including the strength (in milligrams), and how many total doses have you taken 
since your last study visit? Time of last opioid medication taken? 
o 
My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• 
Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven) 
• 
Subjects will be reminded to complete their Medication and Pain Level Diary. (research-driven) 
 
 
Visit 9 (Post-Op day 14 Contact (plus or minus 2 day visit window)): 
• 
Subjects will be contacted by research team in person or via telephone at their Post-Operative Follow Up Visit and asked the 
following questions in this order (in-person) (research-driven): 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average level of pain when 
at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest level of pain since 
your when at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest level of pain since 
your when at rest in the past 24 hours? 
o 
What pain medications are you taking including the strength (in milligrams), and how many total doses have you taken 
since your last study visit? Time of last opioid medication taken? 
o 
My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• 
Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven). 
• 
Subjects will return their Medication and Pain Level Diary and be issued a new one for the remainder of the study. (research-
driven) 
• 
Subjects will be reminded of the two remaining contacts. (research-driven) 
 
Visit 10 (Post-Op day 30 Contact (plus or minus 5 day visit window)): 
• 
Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-
driven): 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average level of pain when 
at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest level of pain since 
your when at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest level of pain since 
your when at rest in the past 24 hours? 
o 
What pain medications are you taking including the strength (in milligrams), and how many total doses have you taken 
since your last study visit? Time of last opioid medication taken? 
o 
My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• 
Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven). 
• 
Subjects will be reminded to complete their Medication and Pain Level Diary. (research-driven) 
 
Visit 11 (Post-Op day 60 Contact (plus or minus 5 day visit window)): 
• 
Subjects will be contacted by research team in person or via telephone and asked the following questions in this order (research-
driven): 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average level of pain when 
at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest level of pain since 
your when at rest in the past 24 hours? 
o 
On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest level of pain since 
your when at rest in the past 24 hours? 
o 
What pain medications are you taking including the strength (in milligrams), and how many total doses have you taken 
since your last study visit? Time of last opioid medication taken? 
o 
My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
o 
Were you diagnosed with post-operative neuralgia at any point following your surgery? 
o 
Were you diagnosed with an inguinal hernia recurrence at any point following your surgery? 


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                                                                                Non-Exempt Human Research 
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o 
Were you diagnosed with a surgical site infection at any point following your surgery? 
• 
Subjects will complete the Post-Operative AAS, and it will be reviewed on the same day of completion. (research-driven). 
• 
The Medication and Pain Level Diary will not be collected from the patient. (research-driven) 
 
Research has shown that a Verbal Numerical Rating Scale of 0-100 (VNRS-101) is a valid instrument for assessing post-operative 
pain, and provides a similar level of accuracy as the Visual Analog Scale (100 millimeter). (17)  The VNRS-101 allows the researchers 
to gain greater precision in the patient’s pain intensity, without requiring the use of an in-person visit to measure the pain level 
using a ruler. 
 
Subjects entering the study with a current prescription for one of the listed opioid medications (codeine, oxycodone, hydrocodone, 
morphine, methadone, oxymorphone, hydromorphone, or transdermal fentanyl) will be allowed to continue taking these opioid 
medications during the study.  Persons who take opioid medications long-term are at risk from opioid withdrawal if they cease 
taking these medications.  The investigators won’t know a priori what each dose will be for each subject, but the investigators will 
record all opioid medication used as a data point.  The doses of all opioid medications will be gathered and converted to morphine 
equivalent units for comparison and statistical analysis. 
 
Baseline laboratory values will be obtained to ensure no underlying kidney or liver disease, which could be exacerbated by the study 
medications. If the subject’s AST or ALT are greater than 3 times the upper limit of normal (AST level > 102 U/L, ALT level > 165 U/L), 
then they will be screen failed. If the subject’s creatinine is greater than 1.3 mg/dL, then they will be screen failed.  
 
Though there are multiple techniques for hernia repair, the standard tension free mesh repair (Lichtenstein repair) is one of the 
most common techniques preformed and is accepted as a standard of care procedure. A polypropylene mesh will be used in all 
patients. A field block of the ipsilateral ilioinguinal nerve and surrounding subcutaneous tissue will be performed during the surgery 
in all patients, using 10 milliliters of 0.25% bupivacaine local anesthesia. The start and end times of surgery and anesthesia will be 
recorded, and the end time of anesthesia will be used for the time zero. To prevent confounders, no epidural or spinal anesthesia 
may be done for study subjects. All opioid medications given during the surgery will be recorded.   
 
Medication usage will be plotted over the post-operative period and average opioid quantities consumed calculated based upon the 
information gathered, after conversion to MEU for each opioid used. Follow-up period for 60 days will include contacts post-op day 
1, 2, 3, 4, 5, 14 +/- 2 days, 30 +/- 5 days, and post-op day 60 +/- 5 days. 
 
3.6.1. Interventions, Observations, or Data Sought: Pain intensity levels and total opioid use in MEUs used by the study subjects to 
treat their post-operative pain with or without a combination of supplemental ibuprofen. 
 
3.6.2. Data Collection and Processing: Data will be collected and recorded in a spreadsheet. At the conclusion of the study, all 
personally identifying information will be removed prior to analysis.  
 
3.6.3. Setting: Active Duty members and DoD beneficiaries age 18 years or older will be recruited at the MOFMC. No special 
populations (e.g., pregnant women, children, military basic trainees, prisoners, detainees) will be recruited. 
 
3.6.4. Date(s): November 2016-November 2018 
 
3.6.5. Source of Research Material: Source of Research Material 
per Participant (Procedures) 
# Routine Care 
# Research Driven 
# Total Procedures 
Fasting Comprehensive Metabolic Panel 
0 
1 
1 
Women of childbearing potential will have a serum or urine 
pregnancy test 
0 
1 
1 
Beck Depression Inventory-II or PHQ-9 depression screen 
0 
1 
1 
Opioid Risk Tool (ORT) 
0 
1 
1 
Pre-Operative Activities Assessment Scale (AAS) 
0 
2 
2 
Post-Operative Activities Assessment Scale (AAS) 
0 
8 
8 
Medication and Pain Level Diary 
0 
2 
2 
Pain Scale (lowest) 
0 
10 
10 
Pain Scale (average) 
0 
10 
10 
Pain Scale (highest 
0 
10 
10 
 
3.6.6. Subjects: Active Duty members and DoD beneficiaries age 18 years or older who are scheduled for an elective unilateral 
inguinal herniorrhaphy will be recruited at the MOFMC. No special populations (e.g., pregnant women, children, military basic 
trainees, prisoners, detainees) will be recruited. 


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3.6.7. Inclusion/Exclusion Criteria:  
Inclusion: 
• Active Duty members and DoD beneficiary patient 18 years or older 
• Elective, open unilateral inguinal herniorrhaphy using Lichtenstein (tension free with mesh) hernia repair technique 
• Agree to take only the prescribed oral analgesic medication (oxycodone/acetaminophen), plus or minus ibuprofen, for the initial 
fourteen-day post-operative period, with allowed exception of any currently prescribed opioid (codeine, hydromorphone, 
morphine, methadone, hydrocodone, oxymorphone, transdermal fentanyl), which can be continued. 
• Agree to honestly complete a depression screening questionnaire, illicit drug use personal history and questionnaire, and physical 
activity assessment questionnaire, with the knowledge that if the patient is an active duty member, this information could result 
in a referral to medical or command authorities for potential Uniform Code of Military Justice (UCMJ) violations or concerns for 
subject health and fitness for duty. 
 
 
Exclusion: 
• Subjects who are pregnant or nursing. 
• Patients who refuse to complete the illicit drug use, physical activity, and depression questionnaires. 
• Strangulated, incarcerated, or otherwise emergent, urgent, and non-elective inguinal herniorrhaphy. 
• Those patients who are allergic to, refuse to take, or are otherwise unable to take oxycodone, ibuprofen, or acetaminophen 
medication orally for post-operative pain management. 
• Patients on pain contracts, or under the care of a pain medicine specialist for management of chronic pain at the time of surgery. 
• Subjects with serum creatinine level > 1.3 mg/dL as measured at the baseline study visit. 
• Subjects with serum aspartate transaminase (AST) greater than 3 times the upper limit of normal (level >102 U/L) 
• Subjects with serum alanine transaminase (ALT) greater than 3 times the upper limit of normal (level > 165 U/L) 
• Subjects who do not speak, read, and write fluently in English. 
• Subjects with a history of cirrhosis. 
• Subjects enrolled in another clinical trial during the same period as their involvement as this study. 
• Subjects, who in the investigator’s opinion, will be unable to complete a pain diary or follow-up visits, or otherwise not comply 
with the study protocol. 
 
3.6.8. Instrumentation: N/A 
4.0.  Human Subject Protection: 
4.1. Recruitment: All potentially eligible patients, presenting to the Surgery Department for a unilateral inguinal herniorrhaphy, will 
be offered an opportunity to participate. Some patients may be patients of the PI or AI, however, they will have the research team 
recruit their patients to prevent any misconception of coercion or undue influence. When a potential subject is identified by the 
treating physician, the Research Staff will be contacted to speak with the patient directly. Surgery Department staff will ask the 
patient if they are willing to speak with the research staff and, if they agree, then the research staff will be contacted to come 
discuss the study with the potential participant. An advertisement will be placed in the Surgery Department. 
 
4.2. Consent Processes: Informed Consent and HIPAA authorization will be sought in advance of any study-related procedures from 
each prospective subject and appropriately documented in accordance with 32 CFR 219.117. Potential candidates will be notified 
about the study either through posted advertisements or by their care provider and will be given the opportunity to consent by one 
of the referred study coordinators. The study coordinator will provide a written copy of the Informed Consent Document (ICD). The 
subject may decline to consent without prejudice. At the subjects’ discretion, they may take the ICD home to discuss further prior to 
making a decision and if they decide they are interested in participating, they can contact the research department the next time 
they present to the Surgery Department. If the subject consents, a copy of the ICD will be given to the subject. No vulnerable 
populations are included in this research study. Subjects who cannot provide Informed Consent will not be allowed to participate. 
No Legally Authorized Representatives (LAR) will be utilized.  
 
4.3 Participation Compensation: Subjects will not be paid for participation in this study. 
 
4.4. Assent Process: N/A 
 
4.5. Benefits: There may be no direct benefits to the subjects for participating in this study. The indirect benefit of this study 
includes the benefit to the military members and society at large regarding the increased knowledge of post-operative pain 
management learned from the results of this study. 
 
4.6. Risks: There is a risk of inadvertent breach of confidentiality. The potential risks to participate in this study are minimal and 
include: 


Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
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The risks and side effects of the standard of care opioid medication given during this study will be provided by the pharmacy along 
with the standard of care prescriptions. Opioid medications such as oxycodone are strong painkillers, and have the potential to be 
abused and can be habit-forming for some persons.  It is important to take only the necessary amount of opioid medication to 
relieve your pain to reduce the risk of developing addiction. 
 
The risks and side effects associated with the venipuncture (Blood Draw), although not likely, include pain, bleeding, bruising, feeling 
light-headed, and a slight possibility of infection 
 
The placebo is a capsule filled with corn starch. There is a chance, although not likely, that subjects have an allergic reaction. The 
signs and symptoms of an allergic reaction include: 
LESS LIKELY and not serious 
RARE and serious 
Hives or skin rash; nausea, stomach cramps, indigestion, vomiting or 
diarrhea; stuffy or runny nose, sneezing, headaches, asthma. 
Anaphylaxis (a potentially life-threatening reaction 
that impairs breathing and sends the body into shock) 
 
 
DRUG NAME 
LIKELY and not serious 
LESS LIKELY and not serious 
RARE and serious 
Ibuprofen 
difficulty with bowel, 
movements; drowsiness, lack 
of strength; relaxed and calm 
feeling; sleepiness or unusual 
drowsiness 
 
upset stomach; heartburn; 
diarrhea; constipation; bloating; 
gas; dizziness; headache; 
nervousness; skin itching or 
rash; blurred vision; ringing in 
ears 
nausea; stomach pain; itching, weight gain; 
discolored urine or stool; jaundice 
(yellowing of skin or eyes); severe 
headache; neck stiffness; chills; increased 
sensitivity to light; bruising; numbness; 
tingling; muscle weakness; fever; sore 
throat 
 
Rare and serious 
• 
There is a risk that completing the Beck Depression Inventory II, Patient Health Questionnaire (PHQ-9) depression screen, Opioid 
Risk Tool (ORT) and/or the Activities Assessment Scale (AAS) may identify a subject as at risk for a mental health condition or a 
substance abuse problem and result in a referral to medical or command authorities for potential Uniform Code of Military 
Justice (UCMJ) violations or concerns for subject health and fitness for duty. 
 
4.7. Costs: N/A 
4.8. Safeguards for Protecting Information: The research consents will be stored in a locked cabinet in a locked room. Medical 
records will be annotated with ICD-10 code Z00.6 to reflect the subject’s participation in a research study. All research data including 
identifiable patient demographics will be kept in a separate electronic database, which will be encrypted, double password 
protected and the access will be restricted. The research data will be coded and any links to identifiable data will be destroyed (an 
approved shredding bin) as soon as the Final Report Approval has been obtained from the IRB. The anonymized research data will 
not be utilized for further research activity beyond the protocol stipulations without additional IRB approval. The Master Key will be 
maintained by the MOFMC Pharmacy, and will have exclusive access to the key in the event of an adverse medication reaction. 
 
4.9. Safeguards for Protecting Subjects: The principal investigator will be responsible for the protocol safety monitoring. The PI will 
make study documents (e.g., consent forms, data pulls) and pertinent hospital or clinical records readily available for inspection by 
the local IRB and oversight staff for confirmation of the study data. 
 
4.9.1. Minimizing Risks: The participants will be monitored by their surgeon, in addition to the research team, principal investigator, 
and co-investigators. Subjects will have access to study personnel should they have any issues, and the study staff and investigator 
contact information will be given to all subjects when enrolled. If there are any adverse events or medical emergencies, they will be 
immediately reported to one of the Investigators and an applicable medical evaluation will be initiated.  The MOFMC Pharmacy will 
maintain the Master Key for the randomization, and the protocol assignment will be unblended if necessitated and requested by the 
treating medical personnel.  Adverse events that could require breaking the protocol would be any medical condition which is 
suspected to be related to the ibuprofen or placebo medication.  This conditions could include anaphylaxis, respiratory failure, 
altered mental status, hives, angioedema, acute kidney injury, or other symptoms of allergic reaction.  In an intention to treat 
analysis, the un-blinded patients will still be analyzed according to their randomization.  In a per protocol analysis, the un-blinded 
patients will be excluded from the analysis, given their deviation from the protocol. Given the special population of Active Duty 
members, the identification of any history of substance abuse can have severe consequences for the Active Duty personnel.  
Likewise, the identification of any mental health issues can have severe consequences for an Active Duty member’s career.  These 
consequences must not be taken lightly by the research staff or investigators, and must be made clear to the prospective subjects at 
the time of screening and enrollment.  The Active Duty personnel approached to consent to this study will be given a thorough 
explanation of the study procedures, including the collection of mental health and substance abuse questionnaires.  The risk to the 
subject will be minimized by allowing subjects to refuse to participate in the study.  Additionally, the subject’s will be informed that 


Version: 1 Dec 2012 
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Study 
they don’t have to complete or answer any question that they do not want to.  At the top of each questionnaire, a sticker will be 
placed that clearly states that the subject is not required to answer any or all questions, without repercussion.  The sticker will state: 
“You are not required to complete any or all questions on this questionnaire.” It will be made abundantly clear that Active Duty 
Members are given the option of completing all, part, or none of the questionnaires.  The informed consent process will include an 
explanation of potential consequences if the subject is identified as having a substance abuse history or current use of illicit drugs, or 
mental health illness.  These consequences include reporting the illicit drug use to the commanding officer, and reporting the mental 
health issues to the subject’s physician, and potentially to the mental health office. 
 
If a positive affirmation on a drug or alcohol questionnaire is identified, then this will be reported to command/law enforcement by 
an Active Duty investigator.  If a positive affirmation on a mental health questionnaire is identified, then that will result in a referral 
to mental health, and could potentially result in a medical evaluation board (MEB). 
 
We will place the subject ID number on all questionnaires in lieu of the subject name to protect confidentiality. 
 
4.9.2. Vulnerable Populations: N/A  
 
4.9.3. Clinical Care: All subjects will receive standard of care regardless of inclusion into this study. If at any time a subject 
experiences any injury or adverse effects, appropriate clinical care will be given or subject will be referred to appropriate provider.  
The MOFMC Pharmacy will maintain the Master Key for the randomization, and the protocol assignment will be un-blinded if 
necessitated and requested by the treating medical personnel.  Adverse events that could require breaking the protocol would be 
any medical condition which is suspected to be related to the ibuprofen or placebo medication.  This conditions could include 
anaphylaxis, respiratory failure, altered mental status, hives, angioedema, acute kidney injury, or other symptoms of allergic 
reaction.  In an intention to treat analysis, the un-blinded patients will still be analyzed according to their randomization.  In a per 
protocol analysis, the un-blinded patients will be excluded from the analysis, given their deviation from the protocol. In the event a 
subject makes a positive affirmation on a drug or alcohol questionnaire, an Active Duty research staff member will report it to command. 
If a subject is identified as at risk for a mental health condition or a substance abuse problem during the study, the Active Duty Principal 
Investigator will report the information immediately to mental health.  
4.9.4. Injury Compensation: N/A 
 
4.9.5. Data Safety Monitoring: The principal investigator will be responsible for the protocol safety monitoring. The PI will make 
study documents (e.g., consent forms, data pulls) and pertinent hospital or clinical records readily available for inspection by the 
local IRB and oversight staff for confirmation of the study data. 
 
5.0. Alternatives: The alternative is to receive standard of care and not to participate in this study. 
 
6.0. Data Analysis:  
6.1. Outcome Measures:  The primary outcome measure is morphine equivalent units (MEU; milligrams) at 8 repeated 
measurements over the first 120 hours of the study. Secondary outcome measures are MEU at 2 repeated measurements over 14 
days and 60 days of the study, sum of the pain intensity difference (SPID) at 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours 
post-surgery, total pain relief (TOTPAR) at 120 hours and 336 hours (14 days) post-surgery, and Activities Assessment Scale (AAS) at 
11 repeated measurements over the 60-day course of the study. The AAS will assess physical activity of the subjects via serial 
questionnaires to determine if the patients with ibuprofen have a quicker return to baseline physical activity. 
 
The use of the BDI-II or PHQ-9 depressive symptom screen and the Opioid Risk Tool and self-perceived risk for opioid addiction will 
assist the investigators in stratifying patients into groups to account for these known confounders.  A tertiary outcome measure will 
be to assess the validity of these tools in predicting prolonged use of opioid medications following surgery.  However, the primary 
reason for these tools is to account for confounding factors in the primary analysis. 
 
6.2. Sample size estimation/power analysis: For the primary outcome measure of MEU, we wish to detect a difference greater that 
1 SD among treatment groups. Prior research (7) indicates patients who have undergone inguinal hernia repair will have a mean 
MEU of 229 mg with 107 SD at 168 hours. Using this outcome measure, a priori power for H0 was assessed using G*Power Version 
3.1.9.2. (34)  The results shown below indicate a total of 160 subjects for each of the four treatment groups and two covariates, BDI 
and ORT having two categories each for a total of 16 groups, with 10 repeated measures will have a power of 0.973 at α = 0.05 to 
detect a 1 SD difference in MEU over repeated measures. A power of this magnitude for the rANOVA will ensure sufficient power for 
post hoc tests having smaller sample sizes. An interim analysis may be performed to determine if results have achieved sufficient 
power to terminate data collection early. 
 
F tests - ANOVA: Repeated measures, between factors 
Input: 
 
Effect size f = 0.44 (moderate) 


Version: 1 Dec 2012 
                                                                                Non-Exempt Human Research 
Study 
β/α ratio = 1 (β=0.05, α=0.05) 
Total sample size  = 160 
Number of groups = 16 
Number of measurements  = 10 
Corr among rep measures  = 0.8 
Output: 
 
 
Noncentrality parameter λ = 37.8 
Critical F = 1.90 
Numerator df  = 15.0 
Denominator df = 144 
α err prob  = 0.027 
β err prob = 0.027 
Power (1-β err prob)  = 0.973 
 
6.3. Statistical Analysis: The experimental design of this study is a mixed effects, randomized complete block design with repeated 
measures. Subject is a random effect as the subjects are a sample randomly selected and randomly assigned to treatment and 
covariate groups. Time of repeated measure and treatment group are fixed effects as these effects cannot be generalized to other 
treatments and times. Statistical analysis will be performed with R Version 3.2.4. (35) 
 
Sample means and standard errors of measurement will be calculated for normally distributed interval variables and medians and 
interquartile ranges (IQR) for non-normally distributed interval variables. Frequency distributions of nominal and ordinal variables 
will be calculated. Null hypotheses of repeated measures will be tested by a mixed effects repeated measures analysis of variance 
(rANOVA), and with appropriate parametric or non-parametric mean/median comparison tests for other variables. In the event the 
rANOVA null hypothesis is rejected, contrasts will be used to investigate effects and differences within time intervals. In the event 
multiple comparison tests are used to investigate effects, the Bonferroni method will be used to correct the level of significance for 
α to p=0.05. (36) 
 
Mr. Danny Sharon, Senior Research Biostatistician Subject Matter Expert for Clinical Research Management under contract W911QY-
11-D-0065, is the statistical consultant support for this study. 
 
6.4 Number of Subjects:  
Number of subjects planned for MOFMC 
Enrolled in Study   
185 
to result in 
160 
completing the study. 
TOTAL NUMBER OF SUBJECTS (nation-wide/study-wide): 185 
 
7. Duration of Study: Approximate duration of the study: 24 months 
8.  Local and External Support Services:  None. 
9.  Intramural (GME) and Extramural Funding Support:  None. 
10. Conflict of Interest: None  
11.  Use of an Investigational New Drug, use of a Drug for a non-FDA approved purpose, use of an investigative device or use of a 
placebo:  This research uses an Investigational New Drug 
      
 
                     [] YES 
[X] NO 
This research uses a FDA approved drug for a non-FDA approved purpose                                                                 [] YES                [X] NO 
This research uses an Investigational Device       
 
 
 
 
     [] YES                [X] NO 
This research uses a placebo. 
 
 
                                                                                    [x] YES                [] NO 
 
12.  Medical Research Area for the Study:  (Pick as many as appropriate) 
[] Analytical Chemistry 
[] Anatomy 
[] Anesthesiology 
[] Biochemistry 
[] Cardiovascular Surgery 
[] Cardiology 
[] Cell Biology 
[] Dentistry 
[] Dermatology 
[] Dietetics 
[] Electrophysiology 
[] Endocrinology 
[] Emergency medicine 
[] Gastroenterology 
[X] General Surgery 
[] Hematology 
[] Histology 
[] Immunology/Allergy 
[] Infectious Disease 
[] Microbiology 
[] Molecular Biology 
[] Neonatology 
[] Neurology 
[] Neurosurgery 
[] Nursing 
[] OB/GYN 
[] Occupational Medicine 
[] Occupational Therapy 
[] Oncology 
[] Ophthalmology 
[] Oral/Maxillofacial Surgery 
[] Orthopedics 
[] Pathology 
[] Pediatrics 
[] Pharmacology 
[] Physical Therapy 
[] Mental Health 
[] Radiology/Imaging 
[] Urology 
[] Wellness 
[] Other (state): 
 
 
13. Attachments: 
1. Form A-Signature Sheet 


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                                                                                Non-Exempt Human Research 
Study 
2. Form A2-Study Personnel 
3. Advertisement 
4. Placebo Justification 
5. Informed Consent Document 
6. HIPAA Authorization Document 
7. Form O: Use of a Drug in Research 
8. Beck Depression Inventory-II (BDI-II) 
9. Patient Health Questionnaire (PHQ-9) depression screen 
10. Medication and Pain Level Diary 
11. Opioid Risk Tool (ORT) 
12. Activities Assessment Scale (AAS) 
13. Centers for Medicare and Medicaid Services’ Hierarchical Condition Category Risk Adjustment Model 

ICF_000.pdf: 
buprofen to Decrease Opioid Use and Post-operative Pain Following 
Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-Controlled, 
Double-Blind, Randomized Controlled Trial  
NCT02929589
27 July 2020


Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-Controlled, 
Double-Blind, Randomized Controlled Trial 
For Protocol Office Use Only: 
FWH20160095H, Scott, ICD, PR 2020 
Version: 0514 
Page 1 of 11 
Volunteer Name: __________________________________________   
WILFORD HALL AMBULATORY SURGICAL CENTER 
INFORMED CONSENT DOCUMENT 
Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A 
Prospective, Placebo-Controlled, Double-Blind, Randomized Controlled Trial 
FWH20160095H 
INFORMATION ABOUT THIS CONSENT FORM:  
You may be eligible to take part in a research study. This form gives you important information about the study. You 
may be asked to sign in more than one place in this document. Please take time to review this information carefully. 
You should talk to the researchers about the study and ask them any questions you may have for them. You may also 
wish to talk to others (for example, your friends, family, or a doctor) about your participation in this study. If you 
decide to take part in the study, you will be asked to sign this form.  Before you sign this form, be sure you understand 
the procedures of the study and what the study is about, including the risks and possible benefits to you. If you are 
taking part in another research study, please tell the researchers or study staff. 
VOLUNTARY PARTICIPATION:  
You do not have to participate in the study if you don't want to participate.  You may also leave the study at any time.  
If significant new findings develop during the course of this study that may relate to your decision to continue to 
participate in the study, you will be informed. If you choose not to participate in this research study or leave before it 
is finished, your decision will not affect your eligibility for care or any other benefits to which you are entitled.   
PRINCIPAL INVESTIGATOR:  
The Principal Investigator (PI) is the researcher directing this study and is responsible for protecting your rights, safety 
and welfare as a participant in the research.  The PI for this study is William Scott, D.O., Maj, Physician, General 
Surgery, Mike O’Callaghan Military Medical Center. 
PURPOSE OF THIS STUDY (Why is this study being done?):  
You are being asked to consider participation in this study because you have been identified as needing an open 
unilateral inguinal herniorrhaphy (hernia repair). The purpose of this research study is to compare the difference in 
post-operative opioid usage in patients who also take ibuprofen versus those who do not take ibuprofen for pain 
relief. This study will enroll approximately 185 subjects. Opioids are a class of narcotic drugs approved by the 
Food and Drug Administration (FDA) used as a pain reliever. Oxycodone is considered an opioid and is a pill taken 
orally (by mouth). Ibuprofen is an anti-inflammatory pain reliever approved by the FDA and is a pill taken orally. 
Acetaminophen is a pain reliever approved by the FDA and is a pill taken orally. Oxycodone, acetaminophen and 
ibuprofen will be the pain relieving medications evaluated for this study. Persons who are already taking opioid 
medications for pain relief before enrolling in the study are still eligible to participate.  You may continue taking 
your currently prescribed opioid medication, as prescribed by your physician, if you meet the criteria to be included 
in this study. Other opioid medications allowed in this study (if currently prescribed by your personal physician) 
include codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone, morphine, methadone, and transdermal 
fentanyl.  You will not be allowed to take other over-the-counter pain medications that are not prescribed to you 
during this study.  This includes acetaminophen, naproxen, or ibuprofen containing medications, or other 
medications within the non-steroidal anti-inflammatory drug (NSAID) class. 


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PROCEDURES: 
If you decide to take part in this research study, you will be asked to sign this consent form. During your participation in 
this study, you will be asked to make four visits with William Scott, D.O., Maj, the Principal Investigator (PI) or study 
staff, and ten additional follow-up phone calls over sixty days to inquire about your pain medication use, to complete 
questionnaires, and to answer questions.   
 
Screening Procedures– a history will be taken after you sign this consent to participate. This screening is done to find 
out if you can continue in the study (screening procedures). This screening visit will add approximately 30 minutes to 
the length of a routine care visit. If you are not allowed to continue in the study, the researcher will discuss the reasons 
with you. The following procedures will be performed. All are research-driven, unless specifically stated as standard of 
care: 
 
Screening Visit: 
• We will discuss the purpose of this study and the required completion of study-related questionnaires and their 
potential impact for active duty members. 
• Obtain your signed Informed Consent Document and HIPAA Authorization. 
• Review your past medical history. 
• We will record information from your pre-operative visits, including your name, date of birth, age, phone 
number, current email address, gender, race, ethnicity, DoD ID, surgical history, family history (first degree 
relative) of opioid use disorder, medical history, height, weight, blood pressure, temperature, pulse, respiratory 
rate, allergies, and medications.  The medication record will include all current prescription and over the counter 
medications, including the use, frequency, and dosage.  Specifically, the use of acetaminophen alone or in 
combination with other medications will be recorded. (standard of care) 
• We will record your history of tobacco, alcohol, marijuana, and other illicit drug use history, and previous non-
prescription use of opioids. 
• Ask what your overall pain score is, from 0 to 100, with 100 being the worst pain imaginable. 
• Ask what your localized pain score is from 0 to 100, with 100 being the worst pain imaginable, which you 
believe is related specifically to the hernia that is scheduled for surgical intervention. 
• You will be instructed to discontinue use of any over-the-counter pain medications, such as ibuprofen, naproxen, or 
acetaminophen containing medications that were not prescribed by the investigators during this study. 
• You will be instructed to take the study medication preferentially if able, and only use the opioid medication as a 
“breakthrough medication.” The total 24 hour dose of acetaminophen from all prescription and over the counter 
medications must not exceed 4 grams. 
• You will be asked the following (approximately 5 minutes to complete): 
o Beck Depression Inventory-II 
o Opioid Risk Tool (ORT). 
o “How likely do you think it is that you will develop an addiction problem from pain medication you take after 
surgery?” and chose from 1 of 4 answers: 1: “not at all”; 2: “unlikely”; 3: “somewhat likely”; or 4: “very 
likely”. 
• You will have a fasting comprehensive metabolic panel test via 1 venipuncture (5-10 milliliters (mls), 1-2 
teaspoons of blood drawn). This test must be completed within 30 days of the surgery, or it will need to be repeated. 
• If you are capable of becoming pregnant, you will have a serum pregnancy test (1 venipuncture or 5-10 milliliters, 
1-2 teaspoons of blood drawn) or urine pregnancy test (10 drops or less than 1 milliliter of urine).  If needed, the 


Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-Controlled, 
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additional 5-10 milliliters for the serum pregnancy test would be gathered via the same venipuncture as the 
fasting comprehensive metabolic panel. 
 
Study Procedures - as a participant, you will undergo the following study-related procedures: 
 
Randomization: 
• You will be randomly assigned (like flipping a coin) into one of the study groups below depending on your past 
opioid use.  Neither you nor your doctor will know which group to which you are assigned. 
o You will be prescribed ibuprofen 800 milligrams by mouth every 8 hours as needed for pain for 5 days, and 1 
to 2 tablets of oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as 
needed for pain for 5 days. Refills will be prescribed if needed through the period of 14 days. 
o You will be prescribed a placebo pill to be taken by mouth every 8 hours as needed for pain and 
oxycodone/acetaminophen 5 milligrams/325 milligrams (Qty. 30) by mouth every 4 hours as needed for pain 
for 5 days. Refills will be prescribed if needed through the period of 14 days. 
 
Day of Surgery: 
• The standard of care local anesthesia used for this type of surgery is bupivacaine. The surgeon will be reminded 
via a note in the medical record. (standard of care) 
• You will be given standard of care pre-operative instructions regarding the use of your pain medications following 
your surgery. The preoperative instructions will include standardized verbal and written instructions: “After your 
surgery, it is expected that you will experience a certain amount of pain for a short period of time. You will be 
prescribed pain medication that you should take only when you are in pain. If you are no longer experiencing 
pain, you should stop taking the medication. If you do not require all of the pain medication that was prescribed, 
you should record the amount of medication that was unused and then properly dispose of the remainder.” 
(standard of care) 
• You will receive treatment medications based on your randomization group.  These prescriptions will be filled at 
the Nellis pharmacy. 
 
Pre-Surgery: 
• Activities Assessment Scale (AAS) 
• You will be asked the following questions: 
o “On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average 
level of pain at rest in the past 24 hours?” 
o “On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest 
level of pain when at rest in the past 24 hours? 
o “On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest 
level of pain when at rest in the past 24 hours? 
• You will be given a Medication and Pain Level Diary and will be instructed to complete it every day for 14 days 
beginning after your surgery. You will be instructed to begin recording your average pain number, highest pain 
number, and lowest pain beginning 24 hours post-surgical incision. You will also be instructed to record the total 
milligrams of each medication used in the previous 24 hours. We will issue you a new one at the 14-day visit.   
 
Post-Surgery: 
• We will record information from your surgery, for example: the start and end times of surgery and anesthesia, 


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how long the surgery lasted, how difficult the surgery was, and which opioid medications the anesthesiologist 
gives at any point during your care. 
• Research staff will record the start and end times of your surgery, record the amounts of standard of care pain 
medications used during your hospital stay, document any standard of care pain assessments that were performed, 
and document the type of anesthesia you received. 
• You will be reminded in the Post Anesthesia Care Unit (PACU) to complete the Medication and Pain Level Diary 
and bring it to your 14 day follow up visit. 
 
Time of Discharge: 
• You will be contacted by a research team member in person or via telephone and asked the following questions: 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest 
level of pain when at rest in the past 24 hours?  
o What pain medications are you taking including the strength (in milligrams), and how many total doses have 
you taken since your surgery? Time of last opioid medication taken? 
o My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• You will be reminded to complete your Medication and Pain Level Diary. 
 
Visits 1-5 (Post-Op day 1 through Day 5 Contact (Each visit every 24 hours plus or minus 4 hour visit 
window): 
• You will be contacted by a research team member in person or via telephone and asked the following questions: 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest 
level of pain when at rest in the past 24 hours?  
o What pain medications are you taking including the strength (in milligrams), and how many total doses have 
you taken since your surgery? Time of last opioid medication taken? 
o My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• You will be asked to complete the AAS (approximately 5 minutes to complete). 
• You will be reminded to complete your Medication and Pain Level Diary. 
 
Visit 6 (Post-Op Day 14 Contact plus or minus 2 day visit window): 
• You will be contacted before or after your Post-Operative Follow-up visit and asked the following questions in 
person or via telephone: 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest 


Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-Controlled, 
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level of pain when at rest in the past 24 hours?  
o What pain medications are you taking including the strength (in milligrams), and how many total doses have 
you taken since your surgery? Time of last opioid medication taken? 
o My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• You will be asked to complete the AAS (approximately 5 minutes to complete). 
• You will return your Medication and Pain Level Diary and be issued new diaries for you to use during the remainder 
of the study. 
• You will be reminded of the two remaining follow-up contacts at 30 days and 60 days. 
 
Visit 7 (Post-Op Day 30 Contact (plus or minus 5 day visit window)): 
• You will be contacted by a research team member in person or via telephone and asked the following questions: 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest 
level of pain when at rest in the past 24 hours?  
o What pain medications are you taking including the strength (in milligrams), and how many total doses have 
you taken since your surgery? Time of last opioid medication taken? 
o My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
• You will be asked to complete the AAS (approximately 5 minutes to complete). 
• You will be reminded to complete your Medication and Pain Level Diary and bring it to your next visit. 
 
Visit 8 (Post-Op Day 60 Contact (plus or minus 5 day visit window)): 
• You will be contacted by a research team member in person or via telephone and asked the following questions: 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what is your average 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your lowest 
level of pain when at rest in the past 24 hours? 
o On a scale of 0-100, with 0 being no pain and 100 being the worst pain imaginable, what was your highest 
level of pain when at rest in the past 24 hours?  
o What pain medications are you taking including the strength (in milligrams), and how many total doses have 
you taken since your surgery? Time of last opioid medication taken? 
o My relief from starting pain is: 0 = none, 1= a little, 2 = some, 3 = a lot, 4 = complete 
o Were you diagnosed with post-operative neuralgia (nerve pain) at any point following your surgery 
o Were you diagnosed with an inguinal hernia recurrence at any point following your surgery? 
o Were you diagnosed with a surgical site infection at any point following your surgery 
• You will be asked to complete the AAS (approximately 5 minutes to complete). 
• The Medication and Pain Level Diary will be collected by the research team. 
• You will be informed what group you were randomized into. 
 
RISKS OR DISCOMFORTS:  
There are risks to taking part in this research study.  One risk is that you may have medication side effects while in the 
study.  Side effects can range from mild to serious.  Serious side effects are those that may require hospitalization, are 


Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-Controlled, 
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life threatening or fatal (could cause death).  The frequency that people experience a certain side effect can range from 
many (likely), few (less likely) or only one or two (rarely).  Side effects from this study will usually go away soon after 
you stop taking the study drugs.  The side effects related to the blood draw will usually go away soon after the blood 
draw has been completed. In some cases, side effects can be long lasting or may never go away. Everyone taking part in 
the study will be watched carefully for any side effects.  However, the study doctors don’t know all the side effects that 
may happen.  Be sure to tell your study doctor immediately, about any side effect that you have while taking part in the 
study. 
 
The following section will describe the risks related to each drug that is part of this research study.  You should talk to 
your study doctor about any side effects or other problems that you have while taking part in the study. There is a risk 
of accidental release of confidential information. 
 
The risks and side effects of the standard of care opioid medication given to you during this study will be provided 
by the pharmacy along with the standard of care prescriptions.  Opioid medications such as oxycodone are strong 
painkillers, and have the potential to be abused and can be habit-forming for some persons.  It is important to take 
only the necessary amount of opioid medication to relieve your pain to reduce the risk of developing addiction. 
 
The risks and side effects associated with the venipuncture (Blood Draw), although not likely, include pain, 
bleeding, bruising, feeling light-headed, and a slight possibility of infection. The placebo is a capsule filled with 
lactose. There is a chance, although not likely, that you may have an allergic reaction. The signs and symptoms of 
an allergic reaction include: 
 
LESS LIKELY and not serious 
RARE and serious 
Hives or skin rash; nausea, stomach cramps, indigestion, vomiting 
or diarrhea; stuffy or runny nose, sneezing, headaches, asthma. 
Anaphylaxis (a potentially life-threatening reaction 
that impairs breathing and sends the body into 
shock) 
 
DRUG 
NAME 
LIKELY and not serious 
LESS LIKELY and not 
serious 
RARE and serious 
Ibuprofen 
difficulty with bowel, 
movements; drowsiness, 
lack of strength; relaxed and 
calm feeling; sleepiness or 
unusual drowsiness 
 
upset stomach; heartburn; 
diarrhea; constipation; 
bloating; gas; dizziness; 
headache; nervousness; skin 
itching or rash; blurred 
vision; ringing in ears 
nausea; stomach pain; itching, weight 
gain; discolored urine or stool; jaundice 
(yellowing of skin or eyes); severe 
headache; neck stiffness; chills; 
increased sensitivity to light; bruising; 
numbness; tingling; muscle weakness; 
fever; sore throat 
 
Rare and serious 
• 
There is a potential for liver injury if more than 4 grams of acetaminophen is consumed in one day. 
• 
There is a risk that completing the Beck Depression Inventory II, Opioid Risk Tool (ORT) and/or the Activities 
Assessment Scale (AAS) may identify you as at risk for a mental health condition or a substance abuse 
problem and result in a referral to mental health and command notification.  If you are an Active Duty member, 
and diagnosed with a mental health and/or substance abuse condition, you may require a Medical Examination 
Board (MEB) referral, be subject to UCMJ action and/or be disqualified from active duty.  You may be 


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reported to command/law enforcement if illicit drug use is affirmed. 
• 
Given the special population of Active Duty members, the identification of any history of substance abuse 
or any mental health issues, could impact an Active Duty members’ military career.  At the top of each 
questionnaire, a sticker clearly states that you are not required to answer any or all questions, without 
repercussion. 
• 
Subjects participating in this study must disclose all over the counter, herbal, and prescription medications to 
the investigators and study staff at time of enrollment and screening.  There is a risk of adverse medication 
interactions if you do not comprehensively disclose all additional medication or supplements that you are 
taking at the time of enrollment. 
 
For more information about risks and side effects, ask one of the researchers or study staff. 
 
As a FEMALE OF CHILDBEARING POTENTIAL wishing to volunteer for this project, you must not be pregnant 
and agree to take a pregnancy test before you participate in this study.  You must also agree to take precautions to 
prevent pregnancy during the course of this study.  The only completely reliable methods of birth control are total 
abstinence or surgical removal of the uterus.  Other methods, such as the use of condoms, a diaphragm or cervical cap, 
birth control pills, IUD, or sperm killing products are not totally effective in preventing pregnancy.  Also, you may not 
breast-feed and participate in this study. If you become pregnant or feel you might be pregnant, contact your provider 
and the study investigator listed in the voluntary participation section. 
 
Are there risks if you also participate in other research studies? Being in more than one research study at the 
same time, may increase the risk to you.  It may also affect the results of the studies.  You should not take part in 
more than one study without approval from the researcher.   
 
There may also be unforeseen risks associated with this or any research study. 
 
WITHDRAWAL FROM THE STUDY:  
If you first agree to participate and then you change your mind, you are free to withdraw your consent and 
discontinue your participation at any time.  Your decision will not affect your ability to receive medical care and 
you will not be penalized or lose any benefits to which you would otherwise be entitled. If you withdraw from the 
study or you have been withdrawn by the PI, you will continue to receive adequate pain medication for standard of 
care, as prescribed by your medical provider. However, the pain medication may or may not include the use of 
ibuprofen. 
 
ARE THERE RISKS RELATED TO WITHDRAWING FROM THE STUDY?  
If you decide to withdraw from this study early, please discuss your decision with the principal investigator.  The 
researchers may ask you to complete study withdrawal procedures at a final study visit. There is no risk to you if 
you do not complete the final withdrawal procedures and you can choose not to participate in them. 
 
COULD YOUR PARTICIPATION END EARLY:  
The researcher may withdraw you from the study prior to the study’s end and the study medication may be stopped, 
without your consent for one or more of the following reasons:  
• 
Failure to follow the instructions of the researchers and study staff. 
• 
The researcher decides that continuing your participation is not in your best interests. 


Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-Controlled, 
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• 
You become ineligible to participate. 
• 
You need treatment not allowed in the study. 
• 
The study is cancelled. 
• 
Other administrative reasons. 
• 
Unanticipated circumstances. 
 
Should you be withdrawn from the study by the Investigator, the Investigator will refer you to your primary care 
provider. 
 
If you lose your status as a military health care beneficiary, you can no longer be included in the study.  Please let 
the Principal Investigator and study staff know as soon as you become aware of your situation. 
 
The Principal Investigator of this study may terminate the study and/or your participation in this study for safety 
reasons.   
 
BENEFITS:  
The investigators have designed this study to learn what standard treatments are effective in controlling pain for 
inguinal hernia repair. There is no guarantee or promise that you will receive any benefit from this study other than 
knowing that the information may help future patients. The possible benefit of your participation in this study is a 
decrease in pain. 
 
COSTS:  Will taking part in this study cost anything?  
The investigators have designed this study so that there is no cost to you to participate in this study other than what it 
will cost you to travel to the research appointment. The extent of medical care provided on this research protocol is 
limited and will be within the scope authorized for Department of Defense (DoD) health care beneficiaries.  Your 
entitlement to medical and dental care is governed by federal laws and regulations. 
 
PAYMENT (COMPENSATION): You will not receive any compensation (payment) for participating in this study. 
 
ALTERNATIVES TO PARTICIPATION:  
Choosing not to participate in this study is your alternative to volunteering for the study.  Your other alternative is to 
receive standard of care treatment for a unilateral inguinal hernia repair, in which Ibuprofen may or may not be 
prescribed with your other pain medications by your attending physician. 
 
CONFIDENTIALITY OF RECORDS OF STUDY PARTICIPATION:  
Records of your participation in this study may only be disclosed in accordance with federal law, including the Federal 
Privacy Act, 5 U.S.C. § 552a, the Health Insurance Portability & Accountability Act of 1996, Public Law 104-109 (also 
known as HIPAA), and their implementing regulations.  DD Form 2005, Privacy Act Statement- Military Health 
Records, contains the Privacy Act Statement for the records.   
 
This is to inform you this study meets the definition of an applicable clinical trial under Section 801 of the Food 
and Drug Administration Amendments Act (FDAAA 801), which requires responsible parties to register and 
submit summary results of applicable clinical trials with ClinicalTrials.gov.  The law applies to certain clinical 
trials of drugs (including biological products) and medical devices.  As a condition for the publication of research 


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results generated by the clinical trial, the International Committee of Medical Journal Editors (ICMJE) also requires 
trial registration through ClinicalTrials.gov.  
 
By signing this consent document, you give your permission for information gained from your participation in this 
study to be published in medical literature, discussed for educational purposes, and used generally to further medical 
science.  You will not be personally identified; all information will be presented as anonymous data. 
 
Your records may be reviewed by the U.S. Food & Drug Administration (FDA), the Air Force, the DoD, other 
government agencies that oversee human research, the 59 MDW Institutional Review Board. 
 
Your consent to participate in this study will be annoted in your medical record.  A copy of this consent will be 
stored by the investigator in a locked cabinet in a locked room. All information about you collected on this study 
will be kept in an electronic database, which will be double password protected and the access will be restricted to 
people involved in this study. Only the pharmacist and the Research Coordinator will have access to the 
randomization records and will not reveal the randomization until the end of the study or in the event of a research 
related adverse event. As soon as possible any link between your identity and the research information will be 
destroyed. The research information collected about you for this study will not be used for any additional research 
activity beyond what you have approved by signing this consent. 
 
The study staff advises that you protect your copy of the informed consent document. A breach of confidentiality 
could occur if you inadvertently lose this document or allow others to view the document. In the unlikely event that 
you experience a loss of confidentiality, the study staff will take appropriate action to assist you.   
 
Complete confidentiality cannot be promised, particularly for military personnel, because information regarding  
potential UCMJ violations or concerns your health and fitness for duty may be required to be reported to appropriate 
medical or command authorities. 
 
ENTITLEMENT TO CARE:  
The researchers have taken steps to minimize the known or expected risks.  However, you may still experience 
problems or side effects, even though the researchers are careful to avoid them.  If you believe that you have been 
harmed, notify the researchers as soon as possible. You may also need to tell your regular doctors. 
 
In the event of injury resulting from this study, the extent of medical care provided is limited and will be within the 
scope authorized for Department of Defense (DoD) health care beneficiaries. 
 
Your entitlement to medical and dental care and/or compensation in the event of injury is governed by federal laws and 
regulations, and if you have questions about your rights as a research subject or if you believe you have received a 
research-related injury, you may contact the Director, 59 MDW Clinical Research Division, (210) 292-7069 or Mike 
O’Callaghan Military Medical Center Human Subject Research Protections Officer, (702) 653-3298. 
 
If you sign this form, you do not give up your right to seek additional compensation if you are harmed as a result of 
being in this study. 
 
 


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PROTECTED HEALTH INFORMATION (PHI) AND PERSONAL IDENTIFYING INFORMATION (PII) 
DATA:  
All de-identified research data that will be used in the database repository will be kept at the Mike O’Callaghan 
Military Medical Center, Clinical Investigation Program and will be handled and disposed of in accordance with 
federal regulations.  No unauthorized individual or agency outside of MOFMC will have access to this database 
without permission of the “Mike O’Callaghan Military Medical Center General Research Data Repository 
(FWH20180064H)”, Manager Col Paul Crawford and the Wilford Hall Ambulatory Surgery Center (WHASC) 59th 
MDW Institutional Review Board (IRB). 
 
The Investigators are asking for your permission to store your de-identified research data in the database repository 
for future use in research studies.  The specifics of these research studies are unknown at this time, but these studies 
will frequently be in the area of acupuncture.  Your stored de-identified research data will be information such as 
gender, age, height/weight, medical history, laboratory tests, blood pressure, waist circumference measurements 
and surgical procedures and post-surgery outcomes.  This data is considered non-identifying information and 
cannot be traced back to you as a donor when added to a database.  The Principle Investigator and Database 
Repository Manager will take every precaution possible to safeguard your information to eliminate the possibility 
of any breach of confidentiality.  This is explained above in the section, “Confidentiality”. 
 
The Database Repository Manager, Col Paul Crawford, is responsible for all de-identified research data stored in 
the repository.  All recipient investigators requesting data from the repository must have approval from the 
Database Repository Manager and must have a research study approved through a DoD Institutional Review Board 
(IRB) and the 59th MDW IRB.  Only de-identified data (no personal identifiers or information) will be released to 
recipient investigators, so specific information can’t be traced back to the donor of the data.  Recipient investigators 
may only receive limited data sets of de-identified information necessary to conduct their research.  Generally, you 
will not be provided with the results of these research studies using your de-identified data from the repository.  
Any results would be of unclear value and unknown clinical meaning, since your de-identified data will be 
combined with other de-identified data from numerous patients used for the study. You cannot request that your de-
identified research data be withdrawn from the database repository since we will have no way to identify you.  This 
request may be accomplished by calling the Database Repository Manager at Col Paul Crawford or mailing your 
request to the following address: Col Paul Crawford, MD, c/o Department of Medical Education, 4700 Las Vegas 
Blvd North, Nellis AFB, NV 89191. 
 
 
_______NO: I do not authorize the storage of my de-identified research data for future use in research studies. 
 
_______YES:  I authorize the storage of my de-identified research data for future use in research studies. 
 
 
 
_____________________________________________________ 
Signature of Study Participant 
 
 


Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy: A Prospective, Placebo-Controlled, 
Double-Blind, Randomized Controlled Trial 
 
For Protocol Office Use Only: 
FWH20160095H, Scott, ICD, PR 2020 
 
 
 
 
Version: 0514 
 
Page 11 of 11 
BLOOD & TISSUE SAMPLES:  
All blood specimens collected will be kept at 99MDG will be handled and disposed of in accordance with federal 
regulations.  Laboratories outside of 99MDG, will not have 99MDG permission to use the samples for any additional 
research. No other blood and tissue samples will be collected. 
 
CONTACT INFORMATION:  
Principal Investigator (PI): The principal investigator or a member of Clinical Investigation Department will be 
available to answer any questions concerning procedures throughout this study. The Principal Investigator is William 
Scott, D.O., Maj, USAF, MC, Phone: (702) 653-3298. 
 
Institutional Review Board (IRB): The PI is responsible for safeguarding your rights as a research subject.  If you have 
any questions about your rights as a research subject, research-related injuries, or any other concerns that cannot be 
addressed by the PI, you can contact the Clinical Investigation Program, 4700 Las Vegas Blvd North, Nellis AFB, NV 
89191 or (702) 653-3298. In addition, if you have any comments, questions, concerns or complaints, you may also 
contact the Chairperson of the 59 MDW IRB, at (210) 916-8251.  Or mail to: 59th Medical Wing/ST, 1100 Wilford 
Hall Loop, Bldg 4430, Lackland AFB, TX 78236-9908 Attn: Authorized Institutional Official. Your consent to 
participate in this study is given on a voluntary basis.  All oral and written information and discussions about this study 
have been in English, a language in which you are fluent. If you agree to participate in this research sign this section.  
You do not waive any of your legal rights by signing this form.   
 
SIGN THIS FORM ONLY IF THE STATEMENTS LISTED BELOW ARE TRUE 
 
• 
You have read the above information. 
• 
Your questions have been answered to your satisfaction.  
• 
Your consent to participate in this study is given on a voluntary basis.  
 
A signed copy of this form has been given to you. 
 
 
_______________________________________  
 
__________________  
VOLUNTEER'S SIGNATURE 
 
 
 
DATE 
 
 
_______________________________________ 
VOLUNTEER'S PRINTED NAME 
 
 
_________________________________________ 
 
____________   
____________________ 
STUDY STAFF SIGNATURE  
 
 
 
DATE  
 
PHONE NUMBER 
 
 
_________________________________________ 
 
 
 
 
PRINTED NAME OF STUDY STAFF