Clinical trial NCT03929640
Conditions: Pain, Postoperative Opioid Use
Sponsor: Milton S. Hershey Medical Center
Start date: 2019-08-05; Completion date: 2020-03-26
Enrollment: 49 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a double blinded randomized controlled trial to test the efficacy of a combination of acetaminophen and ibuprofen administered to patients on schedule compared to ibuprofen alone on the patient's reported pain score on the second post-operative day after Cesarean delivery. The investigators will also record opiate consumption and pain scores throughout the hospitalization of participants, and will survey patients at one and two weeks after surgery regarding opiate consumption and quality of life.

Detailed description:
The investigators have designed a double-blinded randomized, controlled trial to compare a standardized pain regimen of scheduled ibuprofen and acetaminophen to scheduled ibuprofen and placebo. In both arms, the participant will have the ability to ask for medication for breakthrough pain which will be oxycodone. By standardizing and scheduling the administration of ibuprofen with acetaminophen, the investigators hypothesize that total opioid requested and therefore consumed will be decreased in this participants who receive ibuprofen scheduled with acetaminophen. The investigators will primarily assess pain as reported on a 10-point scale mid-day on the second post-operative day. Secondarily, the investigators will collect reported pain scores and total opiate consumption while in the hospital, opiate consumption after discharge, and quality of life as assessed by the World Health Organization Quality of Life "Bref" (WHOQOL-BREF) survey. This information will be obtained via chart review and at-home surveys administered via email on the Research Electronic Data Capture (REDCap) system one and two weeks after surgery.

Enrollment will be performed by study staff. Participants will then be randomized by the institution's Investigational Drug Services (IDS) in REDCap, which uses a randomization table generated by Penn State University (PSU) bio-statisticians. A medication packet will then be prepared and distributed by IDS for the participant containing 20 tablets of acetaminophen 650 mg or placebo based on randomization assignment. The packet will then be sent to nursing staff caring for the patient. Participants will then receive study medication/placebo along with ibuprofen 600 mg (dispensed by the clinical pharmacy) every 6 hours. Participants will be able to request medication for breakthrough pain which will be oxycodone 5 mg or 10 mg depending on reported pain score (one pill for moderate pain, two pills for severe pain). Both ibuprofen and oxycodone will be ordered and dispensed by the clinical pharmacy. Until the participant is deemed able to receive medication by mouth, the participant may receive medication as prescribed by the caring obstetrician and/or anesthesiologist which will be beyond the scope of this trial. Pain scores will be collected and recorded in the medical chart by nursing and assistant staff as part of routine care.

At discharge, participants will receive a standard prescription for 20 tablets of oxycodone 5 mg with directions to take 1-2 tablets every 6-8 hours as needed for breakthrough pain, as is the current group standard at the institution in the Department of Obstetrics and Gynecology.

After discharge, study staff will then conduct a chart review to collect demographic information, review the operative report, and ensure no event took place which would exclude the participant from the study. Study staff will also record total opiate consumption and pain scores.

One week after surgery, the participant will receive an invitation via electronic mail (e-mail) to complete a survey on REDCap which will assess opiate consumption and perceived appropriateness of pain control. Two weeks after surgery, participants will receive two additional invitations; one to complete another survey to assess opiate consumption and perceived appropriateness of pain control, and a second to complete the WHOQOL-BREF. The WHOQOL-BREF survey has been validated to assess four distinct categories of quality of life in women two weeks postpartum. These invitations and reminders have been designed to occur automatically with the assistance of features inherent to the REDCap program. Participants will be considered non-compliant if they fail to complete surveys within three days of receiving their invitation.

Arms: arm 1: Oral administration of ibuprofen 600 mg tablet and placebo tablet every 6 hours arm 2: Oral administration of ibuprofen 600 mg tablet and acetaminophen 650 mg tablet every 6 hours
Interventions: intervention 1: Acetaminophen intervention 2: Placebo intervention 3: Ibuprofen
Intervention descriptions: intervention 1: Acetaminophen 650 mg tablet every 6 hours intervention 2: Placebo oral tablet every 6 hours intervention 3: Ibuprofen 600 mg tablet every 6 hours

Protocol documents:
Prot_SAP_000.pdf: 
Management of Pain After Cesarean:  A Randomized Control (MOPAC) Trial 
Clinical Trials Number: 
NCT0329640 
Study Protocol: 
 Version Date:  07/14/2020 
IRB Approval Date:  01/20/2023 


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HRP-592 - Protocol for Human Subject
Research with Use of Test Article(s)
Protocol Title:
Management Of Pain After Cesarean: A Randomized Control (MOPAC) Trial
Principal Investigator:
Name: Serdar Ural, M.D.
Department: Obstetrics and Gynecology
Telephone: 717-531-8142 (Opt 5)
E-mail Address: sural@pennstatehealth.psu.edu
Version Date:
07/14/2020
Clinicaltrials.gov Registration #:
NCT03929640
Important Instructions for Using This Protocol Template:
This template is provided to help investigators prepare a protocol that includes the necessary information needed by the
IRB to determine whether a study meets all applicable criteria for approval.
1.
GENERAL INSTRUCTIONS:

Prior to completing this protocol, ensure that you are using the most recent version by verifying the
protocol template version date in the footer of this document with the current version provided in the
CATS IRB Library.

Do not change the protocol template version date located in the footer of this document.

Some of the items may not be applicable to all types of research. If an item is not applicable, please
indicate as such or skip question(s) if indicated in any of the instructional text.

GRAY INSTRUCTIONAL BOXES:
o
Type your protocol responses below the gray instructional boxes of guidance language. If the
section or item is not applicable, indicate not applicable.
o
Penn State College of Medicine/Penn State Health researchers: Delete the instructional boxes
from the final version of the protocol prior to upload to CATS IRB (http://irb.psu.edu).
o
Penn State researchers at all other campuses: Do NOT delete the instructional boxes from the
final version of the protocol.

Add the completed protocol template to your study in CATS IRB (http://irb.psu.edu) on the “Basic
Information” page.
2.
CATS IRB LIBRARY:

Documents referenced in this protocol template (e.g. SOP’s, Worksheets, Checklists, and Templates) can be
accessed by clicking the Library link in CATS IRB (http://irb.psu.edu).
3.
PROTOCOL REVISIONS:

When making revisions to this protocol as requested by the IRB, please follow the instructions outlined in
the Study Submission Guide available in the Help Center in CATS IRB (http://irb.psu.edu) for using track
changes.
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Update the Version Date on page 1 each time revisions are made.
If you need help…
University Park and other campuses:
Office for Research Protections Human Research
Protection Program
The 330 Building, Suite 205
University Park, PA 16802-7014
Phone: 814-865-1775
Fax: 814-863-8699
Email: irb-orp@psu.edu
College of Medicine and Penn State Health:
Human Subjects Protection Office
90 Hope Drive, Mail Code A115, P.O. Box 855
Hershey, PA 17033
(Physical Office Location: Academic Support Building
Room 1140)
Phone: 717-531-5687
Email: irb-hspo@psu.edu
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Table of Contents
1.0
Objectives
2.0
Background
3.0
Inclusion and Exclusion Criteria
4.0
Recruitment Methods
5.0
Consent Process and Documentation
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
7.0
Study Design and Procedures
8.0
Subject Numbers and Statistical Plan
9.0
Data and Safety Monitoring Plan
10.0
Risks
11.0
Potential Benefits to Subjects and Others
12.0
Sharing Results with Subjects
13.0
Subject Payment and/or Travel Reimbursements
14.0
Economic Burden to Subjects
15.0
Resources Available
16.0
Other Approvals
17.0
Multi-Site Study
18.0
Adverse Event Reporting
19.0
Study Monitoring, Auditing and Inspecting
20.0
Future Undetermined Research: Data and Specimen Banking
21.0
References
22.0
Confidentiality, Privacy and Data Management
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1.0
Objectives
1.1
Study Objectives
To compare the efficacy of a multimodal pain regimen of both ibuprofen with acetaminophen dispensed on
schedule vs a regimen of ibuprofen with placebo dispensed on schedule to control pain experienced by women
after scheduled, uncomplicated Cesarean delivery.
1.2
Primary Study Endpoints
a.
Pain score mid-day (12 pm – 4 pm) on the second post-operative day (POD), as assessed on a 10-point scale
obtained as part of routine vital signs
1.3
Secondary Study Endpoints
a.
Pain scores assessed through hospitalization on a 10-point scale mid-day (12 pm – 4 pm) on the first post-
operative day, on the morning (4 am – 8 am) of the second and third post-operative days, and the evenings
(6 pm – 10 pm) of the first and second post-operative day.
b.
Total opiate consumption while admitted in total number of oxycodone 5 mg tablets
c.
Total opiate consumption one week after discharge
d.
Total opiate consumption two weeks after discharge
e.
Scores on the WHOQOL-BREF survey two weeks after discharge measured and recorded in each of four
domains of quality of life (physical health, psychological, social relationships, and environment) scaled to the
WHOQOL-100 using procedure outlined in the provided manual from the World Health Organization
2.0
Background
2.1
Scientific Background and Gaps
In July 2017, the ACOG “Green Journal” published several papers which looked at the opiate epidemic
from different angles in relation to obstetrics. In the editorial, Dr. Patrick made note that “by 2012, 259
million prescriptions were written annually in the United States for opioid pain relievers-more than one
for every American adult,” and that nearly a third of women of reproductive age had been prescribed
opiates according to the CDC. However, a growing body of evidence has found that in post-operative
women after a Cesarean section, opiates are often prescribed in excess (1–3) and that when educated
and given the option, patients tended to opt for less pills of narcotic pain medication at discharge (4).
Especially concerning is that some women may have a genetic predisposition to opioid addiction, with
the risk of addiction increasing with total exposures to opiate medication (5). NSAIDs appear to be safe,
even in a population of women with pre-eclampsia with severe features (6), and may not increase
incidence of postpartum hypertension in women with hypertensive disease of pregnancy (7).
Additionally, evidence is beginning to accumulate suggesting non-opiates may not be non-inferior to
opiates (8). Furthermore, synergism has been found between NSAIDs and acetaminophen (9). More
high-quality evidence is needed to re-examine opiate prescribing habits in an effort to provide
guidelines for patients after Cesarean delivery.
We therefore propose a double-blinded, placebo-controlled randomized, controlled trial to compare a
standardized pain regimen of scheduled ibuprofen and acetaminophen to scheduled ibuprofen and
placebo. In both arms, the patient will have the ability to ask for medication for breakthrough pain
which will be oxycodone. By standardizing and scheduling the administration of ibuprofen with
acetaminophen, we hypothesize we can decrease the amount of opiate medication requested and
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decrease total narcotic exposure in this population. We will primarily assess pain as reported on a 10-
point scale mid-day on the second post-operative day. Secondarily, we will collect reported pain scores
and total opiate consumption while in the hospital, opiate consumption after discharge, and quality of
life as assessed by the WHOQOL-BREF. This information will be obtained via chart review and an at-
home survey administered via email on the Research Electronic Data Capture (REDCap) system one and
two weeks after surgery.
2.2
Previous Data
See. 2.1
2.3
Study Rationale
To collect high quality data in order to propose a standardized pain regimen for the average-risk woman
after an uncomplicated Cesarean delivery, which minimizes narcotic usage and exposure.
3.0
Inclusion and Exclusion Criteria
3.1
Inclusion Criteria

All pregnant women

Planned delivery via C-section

Pfannenstiel skin incision

Lower uterine segment transverse hysterotomy

English speaking

Access to electronic mail (email) to be checked at least daily since this project relies heavily on
automated computer software to send survey invitations and reminders via email. Crafting a
methodology to communicate with participants manually without email would add undue
burden to research staff. This criteria should not affect the equitability of research participants
given the general accessibility of email in our study population.
3.2
Exclusion Criteria

Major intra-operative or post-operative complication such that clinician recommends patient
should not receive non-steroidal anti-inflammatory drugs or that patient requires
acetaminophen to treat other condition (ie to treat fever if suspected endometritis)

Unplanned surgery (hysterectomy, bowel/bladder repair)

Allergy or contraindication to study medication

Non-English speaking

Inability to provide informed consent

History of opioid, other illicit substance, or alcohol use disorder either before or during
pregnancy

History of chronic pain requiring medication

Multifetal gestation

Severe renal or hepatic impairment
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3.3
Early Withdrawal of Subjects
3.3.1 Criteria for removal from study

Physician determines that continuing the research would be harmful to the participant

Complication of C-section such that participant cannot receive NSAIDs or requires
acetaminophen for indication other than pain

Inability to tolerate pain regimen

Post-operative complication such that clinician recommends patient should not receive
non-steroidal anti-inflammatory drugs or that patient requires acetaminophen for
indication other than pain (ie: fever)
3.3.2 Follow-up for withdrawn subjects
Subjects may withdraw at any time after enrollment by contacting the PI in writing. Subjects
who withdraw will be asked if information can continue to be obtained from their medical
records. Subjects who do not complete the surveys will also be asked if information can
continue to be obtained from their medical records.
4.0
Recruitment Methods
4.1
Identification of subjects
Study staff will review the Labor and Delivery (L&D) unit schedule for planned Cesarean sections 1-7
days in advance, and certain patient data will be collected and stored in a REDCap database used for
screening, which is separate from the primary project database. The patient’s name, medical record
number, phone number, and scheduled date of surgery will be entered into the REDCap database in a
HIPAA-compliant fashion.
4.2
Recruitment process
4.2.1 How potential subjects will be recruited.
Study staff will review the Labor and Delivery (L&D) unit schedule for planned Cesarean sections
1-7 days in advance, and certain patient data will be collected and stored in a REDCap database
used for screening, which is separate from the primary project database. The patient’s name,
medical record number, phone number, and scheduled date of surgery will be entered into the
REDCap database in a HIPAA-compliant fashion.
Patients will then be contacted via telephone, read a standardized script regarding our study,
and be invited participate. They will also be offered to have an electronic copy or paper copy of
the consent sent to them. They will be informed that they will be approached again on date of
surgery and that we will plan to obtain written consent on the date of surgery if they are
interested in participating. Please see supporting documentation for an example of the
telephone script and the REDCap tool which will be used to track patient enrollment.
Being allowed to review the L&D schedule and contact patients in advance offers significant
logistical benefits and will help promote successful enrollment. Speaking to the patient outside
of the hospital will afford the opportunity to introduce our project in a relaxed atmosphere
without the added stress and anxiety typical of the morning of surgery. Additionally, she will be
allowed the opportunity to receive a copy of our consent form to review at her leisure. On the
date of surgery, patients are often presented with tremendous information, paper forms to sign,
and new people they are meeting who will comprise their surgical and support staff. The
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process of preparing and getting the patient to the operating room leaves little time to allow
study staff to speak with patients ahead of time, and may add increased burden and stress to
the patient.
Since it’s not possible to know when a patient would start requiring oral pain medication after
surgery, enrollment prior to surgery would be ideal and best accomplished by contacting
patients by telephone in advance. Additionally, the REDCap database will be utilized to manage
patient phone calls and enrollment.
We will register the study on the Penn State Clinical and Translational Science Institute (CTSI)
“Study Finder” website. Additionally, a supplemental advertisement sheet (generated by
printing services at Penn State University Hershey Medical Center) will be included in the “36
Week Informational Packet” which is handed out to all women at 36 weeks undergoing a
planned, scheduled C-section. We will also place the fliers in conspicuous locations on the
second floor of the OB clinic located at 35 Hope Drive. The advertisement will contain a QR code
which will link back to the “Study Finder” website. This will allow patients to contact study staff
with any questions. Please see provided supplementary material.
4.2.2 Where potential subjects will be recruited.
On the third floor of the Penn State Hershey Medical Center Hospital Labor and Delivery Unit.
4.2.3 When potential subjects will be recruited.
Potential patients will be approached on their scheduled Cesarean date.
4.2.4 Describe the eligibility screening process and indicate whether the screening process will
occur before or after obtaining informed consent. Screening begins when the investigator
obtains information about or from a prospective participant in order to determine their
eligibility. In some studies, these procedures may not take place unless HIPAA Authorization
is obtained OR a waiver of HIPAA Authorization when applicable for the screening procedures
is approved by the IRB. [For FDA regulated studies, consent for any screening activities would
need to be obtained prior to screening unless specifically waived by the IRB.]
Patient medical records will be reviewed for eligibility prior to study enrollment. The patient’s
name, medical record number, phone number, and scheduled date of surgery will be entered
into the REDCap database. The entries for patients who do decide not to participate in the study
or who are not approached about participating will be deleted from the REDCap database no
later than 30 days after their scheduled C-section date.
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5.0
Consent Process and Documentation
5.1
Consent Process:
Check all applicable boxes below:
Informed consent will be sought and documented with a written consent form [Complete Sections
5.2 and 5.6]
Implied or verbal consent will be obtained – subjects will not sign a consent form (waiver of
written documentation of consent) [Complete Sections 5.2, 5.3 and 5.6]
Informed consent will be sought but some of the elements of informed consent will be omitted or
altered (e.g., deception). [Complete section 5.2, 5.4 and 5.6]
Informed consent will not be obtained – request to completely waive the informed consent
requirement. [Complete Section 5.5]
5.2
Obtaining Informed Consent
5.2.1 Timing and Location of Consent
Informed consent will be obtained in the patient’s room on the Labor and Delivery Unit at Penn
State Hershey Medical Center.
5.2.2 Coercion or Undue Influence during Consent
Informed consent will be obtained in the patient’s room. Patients will be informed verbally and
in writing that participating in this study is entirely voluntary and that her medical care is not
contingent on agreeing to participate in this study.
5.3
Waiver of Written Documentation of Consent
Not applicable
5.4
Informed consent will be sought but some of the elements of informed consent will be omitted or
altered (e.g., deception).
Not applicable
5.5
Informed consent will not be obtained – request to completely waive the informed consent
requirement
Not applicable
5.6
Consent – Other Considerations
5.6.1 Non-English-Speaking Subjects
The inclusion of non-English speaking participants is not planned.
5.6.2 Cognitively Impaired Adults
5.6.2.1 Capability of Providing Consent
The study team members will rely on the assessments of other providers. If the
patient was able to sign the inpatient general consent, she will be considered
capable of consenting to participate in this research study.
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5.6.2.2
Adults Unable to Consent
Adults unable to consent will not be included in this study.
5.6.2.3 Assent of Adults Unable to Consent
Assent will not be required in this study. Only patients who are able to provide
written informed consent will be included.
5.6.3 Subjects who are not yet adults (infants, children, teenagers)
5.6.3.1 Parental Permission
By Pennsylvania law, pregnant minors are allowed to consent and receive medical
care without approval or permission from a parent/guardian. Therefore, parental
permission is not required for minors to participate in this study.
5.6.3.2 Assent of subjects who are not yet adults
Not applicable as in 5.6.3.1.
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
6.1
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
Check all that apply:
Not applicable, no identifiable protected health information (PHI) is accessed, used or
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable]
Authorization will be obtained and documented as part of the consent process. [If this is the
only box checked, mark sections 6.2 and 6.3 as not applicable]
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical
records will be accessed to determine eligibility before consent/authorization has been
obtained). [Complete all parts of sections 6.2 and 6.3]
Full waiver is requested for entire research study (e.g., medical record review studies).
[Complete all parts of sections 6.2 and 6.3]
Alteration is requested to waive requirement for written documentation of authorization
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3]
6.2
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
6.2.1 Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the
individual
6.2.1.1
Plan to protect PHI from improper use or disclosure
Information is included in the “Confidentiality, Privacy and Data
Management” section of this protocol.
6.2.1.2
Plan to destroy identifiers or a justification for retaining identifiers
Study data will be collected and managed using REDCap. Data will be de-identified
with the removal of PHI when abstracted and stored onto this secure system and
there will be no PHI for statistical analysis. We will also need to access the
patient’s medical record throughout the study to obtain information regarding
opiate administration and pain scores while in the hospital and rates of medical
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complications and comorbidities. Additionally, we will review her Cesarean
operative report to ensure no unexpected complications were encountered.
Identifiers will include medical record number, patient name, and date of birth.
6.2.2 Explanation for why the research could not practicably be conducted without access to and
use of PHI
Without PHI, it would not be possible to identify patients eligible to participate in this study.
Additionally, it would not be possible to review their charts to obtain information on opiate
consumption, prescription, and operative complications.
6.2.3 Explanation for why the research could not practicably be conducted without the waiver or
alteration of authorization
Without the ability to access the medical records of patients, it would be impossible to identify
eligible patients to participate in the study in advance. As detailed previously, being able to
speak with patients prior to obtaining consent allows us to introduce the study without the
added anxieties associated with the day of surgery. We will also offer the patient the
opportunity to receive an electronic version of our consent to review at her leisure.
6.3
Waiver or alteration of authorization statements of agreement
Protected health information obtained as part of this research will not be reused or disclosed to any
other person or entity, except as required by law, for authorized oversight of the research study, or for
other permitted uses and disclosures according to federal regulations.
The research team will collect only information essential to the study and in accord with the ‘Minimum
Necessary’ standard (information reasonably necessary to accomplish the objectives of the research) per
federal regulations.
Access to the information will be limited, to the greatest extent possible, within the research team. All
disclosures or releases of identifiable information granted under this waiver will be accounted for and
documented.
7.0
Study Design and Procedures
7.1
Study Design
This is a prospective, double-blinded, placebo-controlled randomized controlled trial
7.2
Study Procedures
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7.2.1 Date of Patient Cesarean Section
Patients who verbally express an interest over the phone will be approached on the date of
surgery for enrollment. If interested, consent would be thoroughly explained and her questions
would be answered.
After thoroughly reviewing the consent, if the patient volunteers to participate, written
informed consent will be obtained. Two copies of the signed consent will then be made with one
given to the participant, another placed on the medical record, and the original to be stored in a
secured cabinet in the Maternal-fetal Medicine Division office.
We will then collect demographic and other information which will be stored in the REDCap
system. The questionnaire will be administered by study staff using an iPad or other tablet-style
mobile device connected to the PSU network.
Participants will then be randomized by Investigational Drug Services (IDS) using our REDCap
randomization table generated by our biostatistician in the Department of Public Health
Sciences to receive either the single (with placebo) or multimodal (with acetaminophen)
regimen. If the online interface is not available, a backup paper system will be utilized and
entries entered into the database later by IDS staff once back online. By design, the module
does not allow the randomization assignment to be edited.
After randomization assignment, the subject will then undergo her Cesarean section by the
labor and delivery assigned team. Her oral post-operative pain regimen will be dispensed as
follows: the clinical pharmacy will dispense scheduled ibuprofen 600 mg every 6 hours and
oxycodone 5 mg every 4 hours 1-2 tablets as needed for breakthrough pain. IDS will then
dispense 40 tablets of either acetaminophen (325 mg each) or placebo based on the
participant’s assignment to be administered by the nurse caring for the patient along with the
scheduled ibuprofen. In the immediate post-operative period, she may receive analgesia as
prescribed by the obstetric and/or anesthesia team, which would be beyond the control of this
trial.
“Breakthrough” pain is defined as pain that is present at a time which no scheduled pain
medication is due (in other words, the pain “broke through” the scheduled medication and
additional medication may be needed). Scheduled medication, either ibuprofen + placebo or
ibuprofen + acetaminophen, will be administered to the patient every 6 hours on schedule
regardless of their reported pain on the pain scale without oxycodone. Oxycodone will be given
if the patient has pain (4 or greater; 1 pill if pain 4-6 or 2 pills if pain 7-10) at a time when no
scheduled medication is due.
Here is a schedule:
0000 - Pain assessed; scheduled medication given
0400 – Pain assessed; may receive oxycodone if pain score 4+
0600 – Pain assessed; Scheduled medication given
0800 – Pain assessed; may receive oxycodone if pain score 4+
1200 - Pain assessed; scheduled medication given
1600 – Pain assessed; may receive oxycodone if pain score 4+
1800 - Pain assessed; scheduled medication given
2000 - Pain assessed; may receive oxycodone if pain score 4+
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In the event that the participant receives patient-controlled analgesia (PCA; typically a narcotic
such as morphine or hydromorphone), she may not receive oral oxycodone until the PCA is
discontinued. This is to prevent over-sedation that may occur if a participant receives excess
opioid medication, since oxycodone too is a narcotic. Typically, a patient may receive a PCA after
surgery if they did not receive long-acting morphine through an intrathecal and/or epidural
catheter. This usually is the case if a patient requires general anesthesia. The PCA administers a
low-dose basal rate of medication, and patients are allowed to request additional medication by
pressing a button. PCAs have a “lockout” feature with parameters pre-set by the anesthesia
team to prevent over-sedation, and they are stopped after 12-24 hours which is the typical time
of action of long-acting intrathecal morphine. While receiving PCA analgesia, our participants
will receive other study medication (ibuprofen and placebo/acetaminophen), since they are
non-narcotic. They will then be ordered for oral oxycodone once the PCA is discontinued.
7.2.2 Post-Operative Day 0 Until Discharge
Patient will receive pain regimen as prescribed: one tablet of ibuprofen and two tablets of either
placebo or acetaminophen 325 mg (for total of 650 mg) every 6 hours.
7.2.3
Hospital Discharge
Pain scores and opiate consumption will be recorded based on chart review. The patient will
receive a prescription for narcotic by physician study team staff which is currently the standard
of the “OB Providers” group at PSHMC: 20 tablets of oxycodone 5 mg with instruction to take 1-
2 tablets every 6-8 hours as needed for breakthrough pain.
7.2.4
One Week Post-Surgery
The patient will receive an invitation via email to complete a survey via REDCap to assess opiate
consumption.
7.2.5
Two Weeks Post-Surgery
Patient will receive an invitation to complete another survey to assess opiate consumption, as
well as the WHOQOL-BREF survey on the REDCap system. The invitations will be sent by email.
7.2.5 Other Considerations
Subjects will be sent daily reminders for 3 days by REDCap via email to complete surveys. After
the third day, the subject will not be eligible to complete the assigned survey. If subject still does
not complete the survey, data that we collected from the subject until this time will still be
utilized and incorporated into the data analysis.
Please see supplements provided for the sample surveys to be administered.
7.3
Duration of Participation
Patients will participate for two weeks.
7.4
Test Article(s) (Study Drug(s) and/or Study Device(s))
7.4.1 Description
We will dispense acetaminophen 325 mg or placebo as study medication. Both will be dispensed
as tablets and will be identical in appearance. Acetaminophen has been approved by the FDA for
use to treat pain.
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7.4.2 Treatment Regimen
Patient will receive ibuprofen 600 mg every 6 hours standing and oxycodone 5 mg 1-2 tablets
every 4 hours as needed for break through pain. In addition, to be dispensed with scheduled
ibuprofen, the patient will also receive either two tablets of placebo or acetaminophen 325 mg
(total dose of 650 mg; tablets coated to be identical in appearance to placebo). There will be no
dose adjustments.
7.4.3 Method for Assigning Subject to Treatment Groups
After enrollment, Investigational Drug Services (IDS) will randomize the participant using the
REDCap module which was built using tables designed by our biostatistician in the Department
of Public Health. A backup system has also been designed and will be available to IDS staff to use
in the event that REDCap is offline (randomization entries are then entered manually into
REDCap once back online by IDS). IDS will then dispense either acetaminophen 325 mg or
placebo tablets to the caring registered nurse. Total number of tablets dispensed will be 40 so
that medication is available for the entire hospitalization.
7.4.4 Subject Compliance Monitoring
Compliance will be assessed by review of the “eMAR” function available on the Powerchart
system, which records when and how patients are dispensed and receive medication.
7.4.5 Blinding of the Test Article
The acetaminophen 325 mg tablets will be blinded with a coating to be applied to the tablet by
IDS staff which will match the size, shape, and color of a corresponding placebo tablet.
7.4.6 Receiving, Storage, Dispensing and Return
7.4.6.1
Receipt of Test Article
A total of 40 tablets (of either acetaminophen 325 mg or placebo) will be
dispensed by IDS to the nurse caring for the patient. The medication will be
transported in a prescription bottle labeled with the patient’s name and
medical record number.
7.4.6.2
Storage
Medication bottles will be stored in either the Pyxis or within locked
cabinets on the nursing “Workstation On Wheels.” The tablets can be
stored at room temperature without additional considerations.
7.4.6.3
Preparation and Dispensing
Study drug (two tablets of either either acetaminophen 325 mg or placebo
tablet) will be dispensed by the nurse caring for the participant on the
postpartum unit at the same time as scheduled ibuprofen 600 mg.
7.4.6.4
Return or Destruction of the Test Article
All unused study medication will be returned to IDS.
7.4.6.5
Prior and Concomitant Therapy
Participant will continue to receive pain medication of ibuprofen 600 mg
every 6 hours and can also ask for additional medication, which will be
oxycodone 5 1-2 tablets every 4 hours as needed. Participants can continue
to receive other therapies and medications typically prescribed while
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postpartum, including prenatal vitamin, stool softener, and iron
supplement.
8.0
Subject Numbers and Statistical Plan
8.1
Number of Subjects
Our target sample size is 144 patients.
8.2
Sample size determination
The primary outcome of this randomized, double-blind trial is the mid-day pain score as assessed using a
10-point scale that will be collected on the second post-operative day. Factoring in 10% subject attrition
and assuming the pain score standard deviation will be 4.0 points, a sample size of 144 subjects (72 per
group) will provide 80% statistical power to detect a pain score difference of 2 points between the two
treatment groups using a two-sided test having a significance level of 0.05.
8.3
Statistical methods
A linear mixed-effects model, which is a subject-specific model, will be used to compare pain scores
between the two treatment groups. This methodology will account for the correlation due to repeated
pain measurements collected over time for each participant. For this model, the dependent variable will
be the pain score and the independent variables will be the treatment group, time, and the interaction
of treatment group and time. For the primary outcome, a contrast will be constructed from this model
to compare the two treatment groups at the mid-day POD 2 time point. Similarly, contrasts will be
constructed from the mixed-effects model to compare the treatment groups at the additional secondary
time points as well. For the mixed-effects model, a first-order antedependence covariance matrix will
assess the residual error associated with the repeated measurements over time per participant. If the
antedependence covariance structure fails to provide model convergence then other covariance
structures will be considered such as unstructured, heterogeneous compound symmetry, and
compound symmetry. Residual diagnostics will be used to determine the appropriateness of model fit
and, if necessary, transformations (e.g., logarithmic) of the outcome will be performed to meet
modeling assumptions. Following our assessment of the initial fit of the model, we will add total opiate
consumption while admitted (e.g., in MEUs) as a covariate to the model to assess its impact, if any, on
the intervention effect.
A mixed-effects model also will be used to compare the two treatments with respect to total opiate
consumption (i.e., in MEUs) collected over time: while admitted, one week after discharge, and two
weeks after discharge. Two-sample t-tests, or Wilcoxon Rank-Sum tests if the data are not normally
distributed, will be used to compare the treatment groups with respect to the secondary continuous
endpoints such as the WHOQOL-BREF survey scores and demographic information such as patient’s age.
Chi-square tests, or Fisher’s exact tests if the expected cell counts are small, will be used to compare the
treatment groups for any categorical demographic variables collected.
9.0
Data and Safety Monitoring Plan
This study involves minimal risk to subjects as it involves standard methods for pain control in patients
undergoing cesarean section.
9.1
Periodic evaluation of data
Not applicable
9.2
Data that are reviewed
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Not applicable.
9.3
Method of collection of safety information
On the REDCap “1 week” and “2 week” survey modules, participants will be queried regarding serious
adverse events (SAEs). Specifically, they will be asked if they experienced any complications requiring
hospitalization. By answering “yes,” that will trigger a free text module in REDCap to allow the
participant to specify the dates and location of her hospitalization, and to include a description of the
complication. An automated email notification will be sent from REDCap to the investigator in real time
when a participant reports a complication requiring hospitalization.
9.4
Frequency of data collection
One week and two weeks post-discharge (via the weekly surveys).
9.5
Individuals reviewing the data
The investigators (PI, Co-PI) will review reported SAEs on a case-by-case basis.
9.6
Frequency of review of cumulative data
Not applicable (SAEs will be reviewed on a case-by-case basis).
9.7
Statistical tests
Not applicable
9.8
Suspension of research
There are no criteria for the immediate suspension of research since all study medication have been FDA
approved for the treatment of pain in doses and schedules being prescribed.
10.0
Risks
Loss of confidentiality is the most significant risk associated with this study. There is also the risk of patient
complaint of suboptimal pain control in the group that’s not receiving acetaminophen. You will not be able to
select which group you’re placed in; this assignment will be made at random by a computer program. You have
a 50% chance of being placed in the group that will receive acetaminophen with scheduled ibuprofen. While
acetaminophen is generally considered safe and can be purchased over-the-counter, it is metabolized by the
liver and too much may lead to liver injury. This could be made worse if you have chronic liver disease or liver
injury, which you may not be aware of. If you have a known history of chronic liver disease or other known
reason why you should not take acetaminophen, you should not participate in this study. To minimize the risk,
acetaminophen dosages have been calculated to be below the daily recommended total dosage.
11.0
Potential Benefits to Subjects and Others
11.1
Potential Benefits to Subjects
None
11.2
Potential Benefits to Others
Will be the first study of its kind to offer high quality evidence examining the effect of a multimodal pain
regimen on pain control and narcotic prescription in this population of women after an uncomplicated
Cesarean section. Could also be included in body of literature hoping to minimize opiate prescription.
12.0
Sharing Results with Subjects
Not applicable
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13.0
Subject Payment and/or Travel Reimbursements
Patients will receive compensation for their completion of surveys. A Clincard will be issued to participants. The
amount loaded on the card will be based on the total number of surveys they complete. The participants will
receive $10 if they complete the one week post-discharge opiate consumption/pain control survey. The
participant will be eligible to receive another $10 if they complete the two week post-discharge opiate
consumption/pain control survey. They will also be eligible to receive $20 if they complete the WHOQOL-BREF
survey, also two weeks after discharge. Total possible compensation will be $40.
14.0
Economic Burden to Subjects
14.1
Costs
The subjects will not be responsible for any additional costs due to participation in the study.
14.2
Compensation for research-related injury
It is the policy of the institution to provide neither financial compensation nor free medical treatment
for research-related injury. In the event of injury resulting from this research, medical treatment is
available but will be provided at the usual charge. Costs for the treatment of research-related injuries
will be charged to subjects or their insurance carriers.
15.0
Resources Available
15.1
Facilities and locations
Penn State Health Hershey Medical Center, 3rd floor labor and delivery and postpartum unit. Post-
operative surveys to be completed online at the patient’s personal residence.
15.2
Feasibility of recruiting the required number of subjects
On average, we perform 1-3 Cesarean sections five days per week on labor and delivery. Assuming an
average of 2 C-section per day, we could theoretically enroll 10 patients per week and 40 patients per
month. Assuming half of the patients agree to participate, we could enroll 20 patients per month and
reach our target sample size of 144 subjects in 7-8 months.
15.3
PI Time devoted to conducting the research
The Co PI is an MFM fellow in the OB/GYN department with ample block research time to conduct and
complete this project. He is entering his second of three years in his fellowship training. The bulk of
patient enrollment could be completed during his third year of training, as he will be predominantly
assigned to research (for at least 9 months). We will also enlist the help of a medical student and
research coordinator to assist in patient enrollment. Assistance from other project members, including
the PI, Program Director, Dr. Serdar Ural, will be provided.
15.4
Availability of medical or psychological resources
Resources are available 24/7 at the Penn State Hershey Medical Center if needed.
15.5
Process for informing Study Team
All members of the research team will have access to the IRB approved protocol and supporting
documents. Additionally, the MFM division has research meetings during which all projects are
discussed. During these meetings, the progress of this study will be reviewed and research members can
clarify duties and expectations to ensure timely completion of the study.
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16.0
Other Approvals
16.1
Other Approvals from External Entities
Not applicable
16.2
Internal PSU Committee Approvals
Check all that apply:
Anatomic Pathology – Penn State Health only – Research involves the collection of tissues or use of
pathologic specimens. Upload a copy of “HRP-902 - Human Tissue For Research Form” in CATS IRB.
Animal Care and Use – All campuses – Human research involves animals and humans or the use of
human tissues in animals
Biosafety – All campuses – Research involves biohazardous materials (human biological specimens
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA
or gene therapy).
Clinical Laboratories – Penn State Health only – Collection, processing and/or storage of extra tubes
of body fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids
that had been collected for clinical purposes but are no longer needed for clinical use. Upload a copy
of “HRP-901 - Human Body Fluids for Research Form” in CATS IRB.
Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves the use of
CRC services in any way.
Conflict of Interest Review – All campuses – Research has one or more of study team members
indicated as having a financial interest.
Radiation Safety – Penn State Health only – Research involves research-related radiation
procedures. All research involving radiation procedures (standard of care and/or research-related)
must upload a copy of “HRP-903 - Radiation Review Form” in CATS IRB.
IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or
intends to hold the IND or IDE.
Scientific Review – Penn State Health only – All investigator-written research studies requiring
review by the convened IRB must provide documentation of scientific review with the IRB
submission. The scientific review requirement may be fulfilled by one of the following: (1) external
peer-review process; (2) department/institute scientific review committee; or (3) scientific review by
the Clinical Research Center Advisory committee. NOTE: Review by the Penn State Health Cancer
Institute (PSCI) Protocol Review Committee or the PSCI Disease Team is required if the study
involves cancer prevention studies or cancer patients, records and/or tissues. For more information
about this requirement see the IRB website.
17.0
Multi-Site Study
Not applicable
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18.0
Adverse Event Reporting
18.1
Adverse Event Definitions
For drug studies, incorporate the following definitions into the below responses, as written:
Adverse event
Any untoward medical occurrence associated with the use of the drug in
humans, whether or not considered drug related
Adverse reaction
Any adverse event caused by a drug
Suspected adverse
reaction
Any adverse event for which there is a reasonable possibility that the drug
caused the adverse event. Suspected adverse reaction implies a lesser degree
of certainty about causality than “adverse reaction”.

Reasonable possibility. For the purpose of IND safety reporting,
“reasonable possibility” means there is evidence to suggest a causal
relationship between the drug and the adverse event.
Serious adverse
event or Serious
suspected adverse
reaction
Serious adverse event or Serious suspected adverse reaction: An adverse event
or suspected adverse reaction that in the view of either the investigator or
sponsor, it results in any of the following outcomes: Death, a life-threatening
adverse event, inpatient hospitalization or prolongation of existing
hospitalization, a persistent or significant incapacity or substantial disruption
of the ability to conduct normal life functions, or a congenital anomaly/birth
defect. Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based
upon appropriate medical judgment, they may jeopardize the patient or
subject and may require medical or surgical intervention to prevent one of the
outcomes listed in this definition.
Life-threatening
adverse event or
life-threatening
suspected adverse
reaction
An adverse event or suspected adverse reaction is considered “life-
threatening” if, in the view of either the Investigator (i.e., the study site
principal investigator) or Sponsor, its occurrence places the patient or research
subject at immediate risk of death. It does not include an adverse event or
suspected adverse reaction that had it occurred in a more severe form, might
have caused death.
Unexpected
adverse event or
Unexpected
suspected adverse
reaction.
An adverse event or suspected adverse reaction is considered “unexpected” if
it is not listed in the investigator brochure, general investigational plan, clinical
protocol, or elsewhere in the current IND application; or is not listed at the
specificity or severity that has been previously observed and/or specified.
For device studies, incorporate the following definitions into the below responses, as written:
Unanticipated
adverse device
effect
Any serious adverse effect on health or safety or any life-threatening problem
or death caused by, or associated with, a device, if that effect, problem, or
death was not previously identified in nature, severity, or degree of incidence
in the investigational plan or IDE application (including a supplementary plan
or application), or any other unanticipated serious problem associated with a
device that relates to the rights, safety, or welfare of subjects.
18.2
Recording of Adverse Events
Subjects will be routinely questioned about AEs while participating in this study.
An abnormal test finding will be classified as an adverse event if one or more of the following criteria are
met:
• The test finding is accompanied by clinical symptoms
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• The test finding necessitates additional diagnostic evaluation(s) or medical/surgical intervention;
including significant additional concomitant drug treatment or other therapy
NOTE: Simply repeating a test finding, in the absence of any of the other listed criteria, does not
constitute an adverse event.
• The test finding leads to a change in study drug dosing or discontinuation of subject participation
in the clinical research study
• The test finding is considered an adverse event by the investigator.
18.3
Causality and Severity Assessments
The investigator will promptly review documented adverse events and abnormal test findings to
determine 1) if the abnormal test finding should be classified as an adverse event; 2) if there is a
reasonable possibility that the adverse event was caused by the study drug(s) or device(s); and 3) if the
adverse event meets the criteria for a serious adverse event.
If the investigator’s final determination of causality is “unknown and of questionable relationship to the
study drug(s) or device(s)”, the adverse event will be classified as associated with the use of the study
drug(s) or device(s) for reporting purposes. If the investigator’s final determination of causality is
“unknown but not related to the study drug(s) or device(s)”, this determination and the rationale for the
determination will be documented in the respective subject’s case history.
18.4
Reporting of Adverse Reactions and Unanticipated Problems to the FDA
18.4.1 Written IND/IDE Safety Reports
Not applicable
19.0
Study Monitoring, Auditing and Inspecting
19.1
Study Monitoring Plan
19.1.1 Quality Assurance and Quality Control
The investigators will permit study-related monitoring, audits and inspections by the Penn State
Quality Assurance Office, IRB and government regulatory bodies of all study related documents (e.g.,
source documents, regulatory documents, data collection instruments, study data, etc.) The
investigators will ensure that capability for inspections of applicable study related facilities.
19.1.2 Safety Monitoring
Adverse events will be identified by the clinician providing care for the patient’s intra-
operatively and post-operatively. They will be educated to report any symptoms concerning for
an AE to the PI and or Co-I. The investigator will confirm that all AEs are correctly entered into
the AE case report forms and will notify the IRB. AEs will also be monitored via the REDCap
“Termination Form” module so that we can monitor how many patients drop out due to AEs.
20.0
Future Undetermined Research: Data and Specimen Banking
Not applicable
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21.0
References
1.
Bateman BT, Cole NM, Maeda A, Burns SM, Houle TT, Huybrechts KF, et al. Patterns of Opioid Prescription and Use
After Cesarean Delivery: Obstet Gynecol. 2017 Jul;130(1):29–35.
2.
Bartels K, Mayes LM, Dingmann C, Bullard KJ, Hopfer CJ, Binswanger IA. Opioid Use and Storage Patterns by Patients
after Hospital Discharge following Surgery. Costigan M, editor. PLOS ONE. 2016 Jan 29;11(1):e0147972.
3.
Osmundson SS, Schornack LA, Grasch JL, Zuckerwise LC, Young JL, Richardson MG. Postdischarge Opioid Use After
Cesarean Delivery: Obstet Gynecol. 2017 Jul;130(1):36–41.
4.
Prabhu M, McQuaid-Hanson E, Hopp S, Burns SM, Leffert LR, Landau R, et al. A Shared Decision-Making Intervention
to Guide Opioid Prescribing After Cesarean Delivery: Obstet Gynecol. 2017 Jul;130(1):42–6.
5.
Donaldson K, Demers L, Taylor K, Lopez J, Chang S. Multi-variant Genetic Panel for Genetic Risk of Opioid Addiction.
Ann Clin Lab Sci. 2017 Aug;47(4):452–6.
6.
Viteri OA, England JA, Alrais MA, Lash KA, Villegas MI, Ashimi Balogun OA, et al. Association of Nonsteroidal
Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features: Obstet
Gynecol. 2017 Oct;130(4):830–5.
7.
Workman P, Spinosa D, Su H-C, Roeder H. Association of NSAIDs with Postpartum Blood Pressure in Women With
Hypertensive Diseases in Pregnancy [26L]: Obstet Gynecol. 2017 May;129:S128.
8.
Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on
Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial. JAMA. 2017 Nov 7;318(17):1661.
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9.
Ong CKS, Seymour RA, Lirk P, Merry AF. Combining Paracetamol (Acetaminophen) with Nonsteroidal
Antiinflammatory Drugs: A Qualitative Systematic Review of Analgesic Efficacy for Acute Postoperative Pain: Anesth
Analg. 2010 Feb;1.
10. Skevington SM, Lotfy M, O’Connell KA. The World Health Organization’s WHOQOL-BREF quality of life assessment:
Psychometric properties and results of the international field trial. A Report from the WHOQOL Group. Qual Life
Res. 2004 Mar;13(2):299–310.
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ICF_001.pdf: 
Management of Pain After Cesarean:  A Randomized Control (MOPAC) Trial 
Clinical Trials Number: 
NCT0329640 
Study Consent: 
 Version Date:  07/14/2020 
IRB Approval Date:  01/20/2023 


Version Date: 07/14/2020
Page 1 of 11 (v.12/19/2018)
CONSENT FOR RESEARCH
Penn State College of Medicine
Penn State Health
Title of Project: Management Of Pain After Cesarean (MOPAC) Trial
Principal Investigator: Serdar Ural, MD
Address: Penn State Health, Department of Obstetrics and Gynecology
Division of Maternal Fetal Medicine
500 University Drive, Hershey, PA 17033
Telephone Numbers: Weekdays: 8:00 a.m. to 5:00 p.m. (717) 531-8142 opt 5. After hours call (717) 531-8521.
Ask for the obstetrician doctor on 24-hour call.
Subject’s Printed Name: _____________________________
We are asking you to be in a research study.
Whether or not you take part is up to you. You can choose not to take part. You can agree to take part
and later change your mind. Your decision will not be held against you, and there will be no penalty or
loss of benefits to which you are entitled.
This form gives you information about the research. Please ask questions about anything that is
unclear to you and take your time to make your choice.
KEY INFORMATION
The following is a short summary of this study to help you decide whether or not to be a part of this
research. More detailed information is provided later in this form. If you have any questions, be sure to
ask the study team.
Why am I being invited to take part in this research study?
We are asking you to take part in this voluntary research study because you are scheduled to have a
Cesarean section (C-section), which is a surgical procedure in which babies are born through the abdomen
(stomach).
What is the purpose of this research study?
The purpose of this voluntary research study is to see if a standardized pain regimen combining ibuprofen
with acetaminophen on schedule is better at controlling pain than a regimen of ibuprofen with placebo,
which is a tablet designed to look like the acetaminophen tablet but which has no therapeutic effect. We
also wish to study how much opiate medication women consume in both groups.
How long will the research study last?
If you agree to take part in this research, you will participate for two weeks after your Cesarean section.
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What will I need to do?
If you take part in this research, your major responsibilities will include:

Allowing the study team to review your medical chart after you are discharged to record your
pain scores and calculate how much opiate pain medication you received in the hospital

Allowing the study team to review your operative report and all notes associated with your
surgery to assess for rates of complications

Completing a survey one week after surgery which asks questions regarding medication
prescription, consumption, and your overall satisfaction with your pain control

Completing two surveys two weeks after surgery: one which will ask additional questions
regarding medication consumption and your overall satisfaction with your pain control, and
another which will ask questions regarding your quality of life.

Please note: you are free to skip any questions that you would prefer not to answer.
What are the main risks of taking part in the study?
For this study, the main risks to know about are: Risk of loss of confidentiality if your information or your
identity is obtained by someone other than the investigators. There is a risk that the pain regimen that you
receive will not be satisfactory to you. While acetaminophen is generally considered safe and can be
purchased over-the-counter, it is metabolized by the liver and too much may lead to liver injury. This could
be made worse if you have chronic liver disease or liver injury, which you may not be aware of. If you have a
known history of chronic liver disease or other known reason why you should not take acetaminophen, you
should not participate in this study. To minimize the risk, acetaminophen dosages have been calculated to
be below the daily recommended total dosage.
What are the possible benefits to me that may reasonably be expected from being in the research?
We cannot promise any benefits to you from taking part in this study. However, possible benefits include
perceived better pain control if you receive our experimental pain regimen and require less opiate pain
medication for breakthrough pain. Results of the study may benefit other people in the future by helping
us learn more about guidance and motivation for future studies to address post-operative pain control in
women who have undergone Cesarean section.
What happens if I do not want to be in this research project?
If you do not wish to participate in this research project, you will receive standard pain medication as
prescribed by the delivering obstetrical team.
DETAILED INFORMATION
The following is more detailed information about this study in addition to the information listed above.
1. Why is this research study being done?
This research is being done to see if a standardized pain regimen combining ibuprofen with
acetaminophen on schedule is better at controlling pain than a regimen of ibuprofen with placebo.
We also wish to study how much opiate medication women consume in both groups.
144 women will take part in this research study at the Penn State Health Hershey Medical Center.
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2. What will happen in this research study?
Date of Patient Cesarean Section
You will be approached by a study team member to see if you are interested in participating in this
research. The consent form will then be thoroughly explained to you and all your questions will be
answered. If you agree to participate, we will proceed with signing the consent. Once signed by you
and the study team member, a copy will be given to you and placed on your medical chart so that
others caring for you will know that you are participating in this project.
We will then collect demographic and other information about your obstetric and medical history.
You are free to skip any questions that you are not comfortable answering.
You will then be randomized (assigned by a computer program) to receive the pain regimen of
ibuprofen plus acetaminophen or ibuprofen plus placebo. You have a 50% chance of being placed in
either group, similar to the odds of flipping a coin and landing on “heads” or “tails.” Neither you nor
the research team will know which study treatment you are receiving, but the research team will be
able to get this information quickly if it is needed to ensure your safety.
You will then undergo your Cesarean section by the obstetrical team per standard of care.
After Cesarean Section until Your Discharge
Before you are able to take medication by mouth, you may receive medication intravenously
(through the IV) or intramuscularly (as an injection) for relief of pain as prescribed by the obstetric
and/or anesthesia team, which would be beyond the control of this trial. Once able to take
medication by mouth, you will be given pain medication as assigned by your grouping
(randomization). You will either receive one regimen (ibuprofen 600mg and placebo scheduled
every 6 hours), or the other regimen (ibuprofen 600mg and acetaminophen 650 mg every 6 hours).
You will also have the option to ask for either one or two tablets of oxycodone 5mg every 4 hours if
you have “breakthrough” pain. “Breakthrough” pain is defined as pain that is present at a time
which no scheduled pain medication is due (in other words, the pain “broke through” the scheduled
medication and additional medication may be needed). Scheduled medication, either ibuprofen +
placebo or ibuprofen +acetaminophen, will be administered every 6 hours on schedule regardless of
your reported pain on the pain scale without oxycodone. Oxycodone will be given if you have pain (4
or greater; 1 pill if pain 4-6 or 2 pills if pain 7-10) at a time when no scheduled medication is due.
Here is a schedule to help you understand when you may receive pain medication, and what
medication may be dispensed:
0000 - Pain assessed; scheduled medication given
0400 – Pain assessed; may receive oxycodone if pain score 4+
0600 – Pain assessed; Scheduled medication given
0800 – Pain assessed; may receive oxycodone if pain score 4+
1200 - Pain assessed; scheduled medication given
1600 – Pain assessed; may receive oxycodone if pain score 4+
1800 - Pain assessed; scheduled medication given
2000 - Pain assessed; may receive oxycodone if pain score 4+
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Hospital Discharge
Pain scores and the drug amount that you have taken will be recorded based on review of your
chart. You will receive a prescription for narcotic which is the standard for all women who have a C-
section at the Penn State Hershey Medical Center: 20 tablets of oxycodone 5 mg of which you can
take 1-2 tablets every 6-8 hours for breakthrough pain. You will be free to take additional over-the-
counter pain medication if you would like.
One Week Post-Surgery
You will receive an invitation via electronic mail (email) to complete another survey online to assess
opiate consumption. You will then receive a daily reminder for three days if the survey is not
complete. If the survey remains incomplete after that time, the invitation link will expire and you
will not be able to complete the survey.
Two Weeks Post-Surgery
You will again receive an invitation to complete another survey to assess opiate consumption, as
well as a quality of life survey (called the WHOQOL-BREF). The invitations will be sent via email. You
will then receive a daily reminder for three days if the surveys are not complete. If the surveys
remain incomplete after that time, the invitation links will expire and you will not be able to
complete the surveys.
What are my responsibilities if I take part in this research?
If you take part in this research, your major responsibilities will include:

Allowing the study team to review your medical chart after you are discharged to record your
pain scores and calculate how much opiate pain medication you received in the hospital

Allowing the study team to review your operative report and all notes associated with your
surgery to assess for rates of complications

Completing a survey one week after surgery which asks questions regarding medication
prescription, consumption, and your overall satisfaction with your pain control

Completing two surveys two weeks after surgery: one which will ask additional questions
regarding medication consumption and your overall satisfaction with your pain control, and
another which will ask questions regarding your quality of life.

Please note: you are free to skip any questions that you would prefer not to answer.
3. What are the risks and possible discomforts from being in this research study?
You will be assigned to a treatment program by chance. The treatment that you receive may prove to
be less effective or to have more side effects than the other research treatment or other available
treatment.
While acetaminophen is generally considered safe and can be purchased over-the-counter, it is
metabolized by the liver and too much may lead to liver injury. This could be made worse if you have
chronic liver disease or liver injury, which you may not be aware of. If you have a known history of
chronic liver disease or other known reason why you should not take acetaminophen, you should not
participate in this study. To minimize the risk, acetaminophen dosages have been calculated to be
below the daily recommended total dosage.
There is also a risk that the pain regimen you receive will not be satisfactory to you. This risk is low
because all medications used in the study have been extensively studied and found to be very good at
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treating pain in the post-operative period. Additionally, these medications are already in use for
treating post-operative pain at the Hershey Medical Center, and you will be allowed to request
additional medication as needed. What makes this study unique is that our regimens will standardize
the schedule of medication administration
There is a risk of loss of confidentiality if your information or your identity is obtained by someone other
than the investigators, but precautions will be taken to prevent this from happening. The confidentiality
of your electronic data created by you or by the researchers will be maintained as required by applicable
law and to the degree permitted by the technology used. Absolute confidentiality cannot be guaranteed.
4. What are the possible benefits from being in this research study?
4a. What are the possible benefits to me?
There is no guarantee that you will benefit from this research. The possible benefit you may experience
from this study is that you may require less opiate pain medication if you receive our experimental pain
regimen.
4b. What are the possible benefits to others?
The results of this research may guide the future studies to address post-operative pain control in
women who have undergone Cesarean section.
5. What other options are available instead of being in this research study?
You do not have to take part in this study to be treated for your condition. Instead of participating in
this research, you could:

Receive normal standard of care for your pain management from the caring obstetrical team.

Be part of a different research study, if one is available.
Before you decide if you want to be in this research, we will discuss the other choices that are available
to you. We will tell you about the possible benefits and risks of these choices.
6. How long will I take part in this research study?
Participation in this study will last approximately 2 weeks after your surgery. This time period will
include one 10-15 minute survey 1 week after your surgery and 2 surveys at 2 weeks after your
surgery that will take 30-45 minutes to complete.
7. How will you protect my privacy and confidentiality if I decide to take part in this research study?
7a. What happens to the information collected for the research?
Efforts will be made to limit the use and sharing of your personal research information to people who
have a need to review this information. Reasonable efforts will be made to keep the personal
information in your research record private. However, absolute confidentiality cannot be guaranteed,
and there may be situations where disclosure is required by law.
In our research files at Penn State Health (PSH) and Penn State College of Medicine (PSU) we will
include these identifiers: your name, address, phone number, date of birth, medical record number,
email address, and a code number.

A list that matches your name with your code number will be kept in a locked file in the Division of
Maternal Fetal Medicine’s research office and only the study team members will have access to it.

Your research records will be labeled with: your code number and your initials and will be kept in a
safe area in the Division of Maternal Fetal Medicine’s research office.
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A copy of this signed consent form will be included in your PSH medical record. This means that
other PSH healthcare providers will know you are in this study.
In the event of any publication or presentation resulting from the research, no personally
identifiable information will be shared.
7b. What will happen to my research information and/or samples after the study is completed?
We may use your research information in future studies with other investigators for future research
without your additional informed consent. Before we use or share your information we will remove
any information that shows your identity.
7c. How will my identifiable health information be used?
In general, under federal law (including the Health Insurance Portability and Accountability Act – HIPAA
or privacy laws) your health information is private. By signing this form, you are authorizing us to
collect, use, and disclose your identifiable health information, sometimes referred to as “Protected
Health Information” or “PHI” under HIPAA, for the purposes of this research study. We will use and
disclose your information only as described in this form, in the PSH Privacy Notice, and as may be
required or allowed under the applicable privacy laws.
The research team may use the following health information:

Past, present, and future medical records, including identifiable information

New health information from tests, procedures, visits, interviews, or forms filled out as part of
this research study.
The following people/groups may see, use, and share your identifiable health information:

PSH/PSU research staff involved in this study

The PSH/PSU Institutional Review Board (IRB), a group of people who review the research study
to protect subjects’ rights and welfare

The PSH/PSU Human Subjects Protection Office

The PSH/PSU Research Quality Assurance Office

Non-research staff within PSH/PSU who need this information to do their jobs (such as for
treatment, payment (billing), or health care operations)

Federal and state agencies (such as the U.S. Food and Drug Administration, the Office for
Human Research Protections, the Department of Health and Human Services, the National
Institutes of Health, and other U.S. or foreign government bodies that oversee or review
research)

People or groups that we hire to do work for us, such as data storage companies, insurers, and
lawyers

Organizations that provide independent accreditation and oversight of hospitals and research

Public health and safety authorities (for example, if we learn information that could mean harm
to you or others, we may need to report this, as required by law)

The PSH/PSU pharmacy

A group that oversees the data (study information) and safety of this research
These groups may also review and/or copy your original PSH/PSU records while looking at the results of
the research study. It is possible that some of the other people/groups who receive your health
information may not be required by Federal privacy laws to protect your information. We share your
information only when we must, and we ask anyone who receives it from us to protect your privacy.
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Sometimes a Principal Investigator or other researcher moves to a different institution. If this happens,
your identifiable health information and samples may be shared with that new institution and their
oversight offices. PHI will be shared securely and under a legal agreement to ensure it continues to be
used under the terms of this consent and HIPAA authorization.
We may remove identifying information from your protected health information. Once we do this, the
remaining information will not be subject to the privacy laws. Information without identifiers may be
used or disclosed with other people or organizations for purposes besides this study.
Because research is an ongoing process, your permission for the use, storage and sharing of your health
information will continue indefinitely.
Your privacy rights:

You have the right to refuse to sign this form that allows us to use and share your health
information for research; however, if you don’t sign it, you will not be able to take part in this
research study.

You have the right to withdraw your permission for us to use or share your health information
for this research study. If you want to withdraw your permission, you must notify the person in
charge of this research study in writing using the address on the front of this form. Once
permission is withdrawn, you cannot continue to take part in the study.

If you withdraw your permission, we will stop collecting health information about you for this
study; we may continue to use and share your health information that we already have if it is
necessary for safety and scientific soundness of the research study; and we will not be able to
take back information that has already been used or shared with others.

You have the right to see and get a copy of your health information that is used or shared for
treatment or for payment. However, you may not be allowed to see or copy certain health
information that is a part of this research study. This is only for the period of the study. You will
be allowed to see that information when the entire research study is complete.
8. What are the costs of taking part in this research study?
8a. What will I have to pay for if I take part in this research study?
For costs of medical services for care you would receive even if you were not in this research study:

You and/or your insurance company will be responsible for the cost of routine medications,
tests and procedures that you would receive even if you were not in this research.

You and/or your insurance company will be billed for the costs of these routine tests and
procedures in the usual manner.

You will be responsible for any co-payments, co-insurance and deductibles that are standard
for your insurance coverage.

You will be responsible for any charges not reimbursed by your insurance company.

Some insurance companies may not pay for routine costs for people taking part in research
studies. Before deciding to be in this research you should check with your insurance company
to find out what they will pay for.

You will not be required to pay for medication dispensed by the study (placebo or
acetaminophen 650 mg tablets).
If you have any questions about costs and insurance, ask the research study doctor or a member of the
research team.
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8b. What happens if I am injured as a result of taking part in this research study?
It is possible that you could develop complications or injuries as a result of being in this research study.
If you experience a side effect or injury and emergency medical treatment is required, seek
treatment immediately at any medical facility. If you experience a side effect or injury and you
believe that emergency treatment is not necessary, you should contact the principal investigator
listed on the first page of this consent form as soon as possible and the principal investigator will
arrange for medical treatment. You should also let any health care provider who treats you know
that you are in a research study.
PSH/PSU compensation for injury

There are no plans for PSH/PSU to provide financial compensation or free medical treatment
for research-related injury.

If an injury occurs, medical treatment is available at the usual charge.

Costs will be charged to your insurance carrier or to you.

Some insurance companies may not cover costs associated with research injuries.

If these costs are not covered by your insurance, they will be your responsibility.
When you sign this form you are not giving up any legal right to seek compensation for injury.
9. Will I be paid to take part in this research study?
Reimbursement and payment must occur in accordance with PSU Research Protection Guidelines:
RPG03, as outlined below.
Payment must be issued by Greenphire ClinCard

The subject must be paid by deposit onto the card, which may be used as a credit or debit
card;

Social security number must always be collected, but it will only be used to generate a 1099
form for tax reporting purposes for money offered as a stipend. Reimbursement dollars will
not be counted towards tax reporting purposes.

If you believe that you cannot use the Greenphire ClinCard, please contact the Controller’s
Office at controller@pennstatehealth.psu.edu.
If you complete the one week opiate consumption/pain control survey, you will be receive $10. If you
complete the two week opiate consumption/pain control survey, you will receive $10. If you complete
the quality of life survey, you will receive $20. Therefore, the total compensation you could receive is
$40. If you do not complete a survey for any reason, you will receive compensation only for the surveys
you have completed. Payments will be provided by a Greeenphire ClinCard which will be mailed to your
home address upon completion of your participation in the study.
This reimbursement will be issued by an external company called Greenphire, which will issue your
reimbursement. You will be issued a ClinCard, which is a debit card that your funds are loaded onto and
can be used at your discretion. The research team will give Greenphire some personal information
about you, as described below. Greenphire will only use your personal information to process this
reimbursement and will not share it with anyone for any other purpose. Details of the debit card system
are explained on an additional sheet. If you lose the card, you may be responsible for the replacement
fee.
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When the survey(s) are completed, funds will be approved and loaded onto your card. The funds will be
available within 2-3 business days. In order to assign a ClinCard to you and load funds onto the ClinCard,
Greenphire will need your Study/Subject ID, Name, Address, and Social Security Number.
You will have the option to receive updates related to payment alerts via text message and/or email
message. Standard text messaging rates will apply. In order to send you messages Greenphire will need
your Mobile Phone Number and/or E-mail Address.
10. Who is paying for this research study?
Funds from the Department of Obstetrics and Gynecology, Penn State College of Medicine will be used
to support this research. The Penn State Addiction Center is providing computer equipment.
11. What are my rights if I take part in this research study?
Taking part in this research study is voluntary.

You do not have to be in this research.

If you choose to be in this research, you have the right to stop at any time.

If you decide not to be in this research or if you decide to stop at a later date, there will be no
penalty or loss of benefits to which you are entitled.
If you stop being in the research, already collected data may not be removed from the study database.
You will be asked whether the investigator can collect medical information from your routine medical
care. If you agree, this data will be handled the same as research data. If you withdraw completely from
the research study, no further information will be collected and your participation will end. You may
discontinue taking part at any time without penalty or loss of benefits to which you are otherwise
entitled.
Your research doctor may take you out of the research study without your permission. Some possible
reasons for this are: continuing the research would be harmful because of serious side effects, you
cannot receive NSAIDs or you require acetaminophen for a reason other than pain.
During the course of the research you will be provided with any new information that may affect your
health, welfare or your decision to continue participating in this research.
12. If I have questions or concerns about this research study, whom should I call?
Please call the head of the research study Dr. Serdar Ural at 717-531-8142, option #5 or the Obstetrics
doctor on 24-hour call at (717) 531-8521 if you :

Have questions, complaints or concerns about the research.

Believe you may have been harmed by being in the research study.
You may also contact the research protection advocate in the PSH Human Subjects Protection Office (HSPO)
at (717) 531-5687 if you:

Have questions regarding your rights as a person in a research study.

Have concerns, complaints or general questions about the research.

Have questions about your privacy and the use of your personal health information.

You may also call this number if you cannot reach the research team or wish to offer input or to talk
to someone else about any concerns related to the research.
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You may visit the Penn State College of Medicine’s Clinical Research web site at
http://med.psu.edu/clinical-research/faqs for:

Information about your rights when you are in a research study;

Information about the Institutional Review Board (IRB), a group of people who review the research
to protect your rights; and

Links to the federal regulations and information about the protection of people who are in research
studies. If you do not have access to the internet, copies of these federal regulations are available
by calling the HSPO at (717) 531-5687.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law.
This Web site will not include information that can identify you. At most, the Web site will include a
summary of the results. You can search this Web site at any time.
INFORMED CONSENT AND AUTHORIZATION TO TAKE PART IN RESEARCH
Signature of Person Obtaining Informed Consent
Your signature below means that you have explained the research to the subject or subject
representative, provided the subject or subject representative an opportunity to discuss and consider
whether or not to participate in the research, and have answered any questions about the research.
______________________________
__________
______
________________
Signature of person who explained this research Date
Time
Printed Name
(Only approved investigators for this research may explain the research and obtain informed consent.)
Signature of Person Giving Informed Consent and Authorization
Before making the decision about being in this research you should have:

Discussed this research study with an investigator,

Read the information in this form, and

Had the opportunity to ask any questions you may have.
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Your signature below means that you have received this information, have asked the questions you currently
have about the research and those questions have been answered. You will receive a copy of the signed and
dated form to keep for future reference.
Signature of Subject
By signing this consent form, you indicate that you voluntarily choose to be in this research and authorize
your information to be used and shared as described above.
___________________________
__________
______
________________
Signature of Subject
Date
Time
Printed Name
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