A Randomized-controlled Trial of Post-operative Opiate Quantities After Urogynecologic Surgery
Phase: NA
Conditions: Postoperative Pain, Opioid Use
Sponsor: The Cleveland Clinic

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A randomized-controlled trial of post-operative narcotic quantities after urogynecologic surgery 
 
Emily RW Davidson, MD; Fellow in Female Pelvic Medicine and Reconstructive Surgery. Center of 
Urogynecology and Pelvic Floor Disorders; Obstetrics/Gynecology and Women’s Health Institute at the 
Cleveland Clinic 
 
Marie Fidela Paraiso, MD; Center of Urogynecology and Pelvic Floor Disorders; Obstetrics/Gynecology and 
Women’s Health Institute at the Cleveland Clinic 
Cecile Unger, MD, MPH; Center of Urogynecology and Pelvic Floor Disorders; Obstetrics/Gynecology and 
Women’s Health Institute at the Cleveland Clinic 
 
BACKGROUND 
The opiate abuse epidemic in the United States is a costly and deadly issue. Opiate overdose leads to 78 deaths 
each day, and half of these deaths involve prescription opiates1. Heroin overdose is also relevant given that 
three out of four heroin users reported abusing prescribed opiates prior to using heroin2. Recent government-led 
initiatives have attempted to reduce opiate prescriptions for patients with chronic pain1,3, but there are currently 
no guidelines regarding quantities of prescribed opioid medications for post-operative pain management. 
Balancing pain control with limiting opiate exposure may be a difficult task, especially in patients at risk for 
adverse events with narcotic use or potential diversion of prescribed opiate into abuse or addiction. Older 
patients may be at increased risk of development of chronic opiate abuse; a retrospective analysis of over 
390,000 patients found that in opiate-naïve patients 66 years old and older who underwent a short-stay surgery 
and received post-operative opiates, these patients were 44% more likely to become a long-term opiate user by 
post-operative year one than those who did not receive post-operative opiate medications.4  
 
In routine post-operative practice, many surgeons likely provide a standardized amount of pain medication after 
a procedure for all patients in anticipation of expected pain, potentially more than necessary in order to avoid 
patient phone calls. In Bates et al’s survey of post-operative urology patients, there was an excess of prescribed 
opiates for over two thirds of patients5. Most surveyed patients did not how to safely dispose of unused pills, 
and the majority of patients kept the excess at home. The median number of pills used was less than ten for 
minimally invasive procedures and less than twenty for the more invasive procedures despite prescribed 
numbers around twenty and thirty respectively.  This meant that over 40% of prescribed medication was going 
unused and potentially available for diversion. Recent results from a similar survey in a urogynecology patient 
population showed that patients are using approximately one third of prescribed opiate medications after 
minimally invasive urogynecology surgery6. This study also showed that patients given a large quantity of 
medication used more of the medication. Given these findings that physicians are not appropriately prescribing 
opiate medications which may be potentially contributing to the opiate abuse epidemic, it is important to 
determine an appropriate amount of pills to prescribe after surgery so that surgeons can be better stewards of 
these potentially dangerous prescriptions. The aim of this study is to provide information to inform future 
guidelines for prescription opiates after urogynecologic surgery. 
 
HYPOTHESIS 
Patients prescribed fewer or no opiates will have no difference in satisfaction with pain control. 
 

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STUDY DESIGN 
Randomized controlled non-inferiority clinical trial 
 
 
Primary Outcome:  
Patient satisfaction with pain control 
 
 
 
 
 
 
 
Secondary Outcomes: 
1. Number of opiate tablets used by patients 
2. Number of patient requests for narcotic medication 
3. Number of unscheduled visits for pain control 
4. Time of return to baseline activities 
5. Side effects of medications (such as constipation, dizziness) 
6. Patient use of other analgesics (such as ibuprofen, acetaminophen) 
7. Patient willingness to dispose of excess pills 
Study Population: Study subjects will be recruited from patients that present to the Center of Urogynecology 
and Pelvic Floor Disorders in the Department of Obstetrics and Gynecology at their preoperative visit at Main 
Campus. 
 
Inclusion Criteria: 
1. Women 18 years or older 
2. Women scheduled to undergo minimally invasive surgery within the urogynecology division at 
Cleveland Clinic with a plan to stay one night in the hospital afterwards for a benign indication which 
includes: 
o Vaginal hysterectomies with prolapse repair 
o Sacrospinous ligament fixations 
o Hysteropexy 
o Sacrocolpopexy 
3. Women able to provide consent for research participation and to sign an informed consent 
 
Exclusion Criteria: 
• Women with chronic pain or chronic pain syndrome 
• Women undergoing concurrent bowel surgery 
• Women with pre-operative chronic opiate use 
• Inability to comprehend written and/or spoken English 
• Inability to provide informed consent 
• Inability to take oxycodone 
• Inability to take acetaminophen due to allergy or liver disease 
• Women will be excluded if they undergo an unplanned laparotomy 

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• Pain catastrophization score 
o This is a previously published instrument to assess how patient’s handle pain; those who score 
high on this instrument have increased rumination over pain, increased sense of helplessness, and 
magnification of pain. Those who score 30 or more (75%ile) will be excluded as they have a 
higher post-operative pain rating.7 
 
Safety/Data Monitoring: 
Any adverse event or unanticipated events will be reported immediately to the IRB using IRB WebKit.  All 
events will be recorded and kept in a research binder assigned to this study in a locked office.  Monthly reviews 
during the study period will be done by all involved study staff members to ensure that events are not occurring, 
and if they are, that they are being handled and reported properly. The study will be terminated if over 50% of 
patients in the decreased opiate group request more or stronger medication during interim analysis or have 
>20% decreased satisfaction to the control group; this will be assessed monthly at the reviews mentioned above.    
 
STUDY PROCEDURES 
 
Study Identification and Recruitment 
Potential subjects will be identified by members of the Center for Urogynecology and Pelvic Reconstructive 
Surgery at the Cleveland Clinic Main Campus.   At the time of decision for surgery, attending staff who have 
been counseled about how to discuss the study will bring up the study. Fliers will be available to give to 
patients. Patients will be offered a visit with research staff at this time. They also will have the opportunity to 
meet research staff at their preop visit which is when consent forms would be signed and prescriptions given.  
Phone calls from research staff will also be made to interested patients or potential subjects. Eligible patients 
who agree to participate will be provided written informed consent administered by the collaborators listed on 
the IRB. Consents can be obtained at the Cleveland Clinic Main Campus or Fairview hospital. 
Randomization 
All subjects will be scheduled for surgery by their surgeon. Consenting patients who meet inclusion criteria will 
be randomized into one of two arms: “routine opiate prescription” or “decreased opiate prescription” according 
to a computer-generated randomization schedule with random block sizes with the use of the JMP statistical 
software.   The routine arm will receive twenty-eight tabs of oxycodone at discharge - thirty was  the usual 
number prescribed for these surgeries, but new opiate prescribing guidelines limit the amount prescribed as 28 
tablets based on morphine equivalent doses and a 7 day prescription limit. The decreased prescription arm will 
receive five tabs of oxycodone. All subjects will be instructed to use the opiate pills only as a back-up pain plan 
after the NSAID and acetaminophen. All subjects will be instructed to use the same schedule: schedule 
ibuprofen and acetaminophen for 3 days followed by these as needed.    Subjects will have their prescriptions 
filled on day of discharge at the Cleveland Clinic pharmacy based on the randomization in addition to the 
following medications that per protocol all patients will receive unless contraindicated due to 
allergy/medication interaction: Colace (100mg tablets to take PO BID, #60), Miralax (17gm packets to take PO 
daily, #30), and ibuprofen (600mg tablets to take PO every 6 hours for 3 days postoperatively then as needed, 
#60.  The use of scheduled NSAIDs is based on benefit of multimodal therapy in an effort to minimize opiate 
use.  Despite these medications’ potential effect to decrease effect seen between the study groups, their use in 
the trial provides increased clinical applicability.   
 
Dispensing Medication 

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If the patient approves to participate in the study, they will receive the allotted post-operative medication at time 
of discharge prescriptions for their postoperative medications as above at their preoperative visit.  In addition, 
patients will also receive a sealed envelope with a prescription for a back-up supply of pain medication (10 pills 
of oxycodone 5mg). They will be instructed to fill these only if they run out of the previous supply and are still 
requiring stronger pain medication. Because of the way the prescription will be written (with instructions to the 
pharmacy not to fill before the date of post-operative day 2), they cannot automatically fill the same day as 
discharge (post-operative day 1) and this prescription is only valid for two weeks after this date. They will be 
instructed that if they require more pain medication than this, they will need to be seen. Patients will be 
provided with a daily pain and activity diary and medication log. At their 6-week postoperative visit, patients 
will bring in this diary as well as any remaining opiate medication and/or the sealed envelope containing the 
back-up prescription.  
 
Data Collection & Management: 
Other than the study forms (see attached), the electronic medical record (EPIC) will be used to obtain basic 
medical information including medical problems, height & weight/BMI, past surgeries, current medications, 
and allergies. 
 
Preoperative data will include the following: 
• Patient age, race and ethnicity, menopausal state, tobacco use, BMI, education level, patient income 
level 
 
Peri-operative data will include the following: 
• Surgery performed 
• Surgical complications 
• EBL 
• Hospital complications 
• Delayed complications 
• Prescribed medications (with detail given to agreement with randomization arm and if multimodal 
agents were not prescribed and for what reason) 
• Post-operative pain scores at last RN assessment on day of discharge 
• Medication records of quantity of narcotics used perioperatively (to be standardized to morphine 
equivalents) 
 
Postoperative data will include the following: 
• Patient’s daily pain diaries including medications used which can be completed on paper diaries to be 
turned in at their post-operative visit OR entered electronically using REDCap (see below) 
• Patient satisfaction with post-discharge pain control 
• Patient’s daily activities 
• Whether patient received additional narcotic prescription through the following: 
o Study protocol through a phone call 
o Study protocol through an outpatient visit 
o Other (e.g. emergency room, urgent care) 
• Patient satisfaction with bowel symptoms and constipation treatment as needed 
• Number of pills used (as calculated by pill count or pain diary if pills not returned) 
• Number of remaining pills (as calculated by pill count or pain diary if pills not returned) 
• Patient’s willingness to destroy remaining pills 
 

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Protection of each subject’s personal health information will be a priority in this study. One master excel file 
containing subject personal information including name and medical record number will be kept in a password-
protected file, on a designated protected research drive on a password-protected computer in a locked office at 
the Cleveland Clinic. In that file, each subject will be assigned a subject identification number that will be used 
for the purposes of data collection in order to de-identify subjects.  
All paper forms used for data collection will be kept in a research cabinet dedicated to this project which will be 
locked at all times, in a locked office at the Cleveland Clinic. All forms will contain de-identified information – 
identification numbers will correspond to the subjects listed in the master excel file.  
All study data will be transferred and managed electronically using REDCap (Research Electronic Data 
Capture). Each subject will be entered into REDCap using the assigned identification number from the master 
excel file. REDCap is a secure, web-based application designed to support data capture for research studies, 
providing user-friendly web-based case report forms, real-time data entry validation, audit trials, and a de-
identified data export mechanism to common statistical packages. They system was developed by a multi-
institutional consortium which was initiated at Vanderbilt University and includes the Cleveland Clinic. The 
database is hosted at the Cleveland Clinic Research Datacenter in the JJN basement and is managed by the 
Quantitative Health Sciences Department. The system is protected by a login and Secure Sockets Layers (SSL) 
encryption. Data collection is customized for each study based on a study-specific data dictionary defined by 
the research team with guidance from the REDCap administrator in Quantitative Health Sciences at the 
Cleveland Clinic. The REDCap database will include potential identifiers to enable online surveys. The 
collected potential patient identifiers include: 
Date of Birth 
Surgery Date 
Subject Email (that they provide for the study) 
 
Analysis Plan: 
Sample size calculation was based on data suggesting a 92% satisfaction with a regimen of pain control similar 
to the study’s control group. With a power of 90% at an alpha of 5%, we would require 57 subjects per arm. 
With a drop-out rate of 3% (based on 2016 post-operative visit “no-show” rates for the Urogynecology division 
– the timepoint when the primary outcome is collected), 59 subjects per arm will be recruited for a total goal 
recruitment of 118. 
Continuous data will be analyzed using Student’s t test or the Mann-Whitney U test, and proportions will be 
compared using a χ2 or Fisher’s exact test, as appropriate. P values ≤ 0.05 will be considered statistically 
significant, and we will use JMP as our statistical package to perform these analyses.  
 
STUDY COST/BUDGET 
 
The study budget is estimated at $10,000.  Estimated sample size is 59 patients per arm in each group for a total 
of 118 subjects.  

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Patient reimbursement: 
• $10 for parking at post-op visit x 118 subjects = $1180 
• $25 for diary completion x 118 subjets = $2950 
Research Nurse Support: 
• Salary: $4586 
• Fringe: $1284 
 
 
 

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Summary of tasks for study: 
 
 
Preop 
Day of Surgery 
Post-operative:       
Daily Basis 
Post-operative:       
As Needed Basis 
Post-operative:       
Post-op visit 
Informed 
consent 
X 
 
 
 
 
Demographic 
data 
X 
 
 
 
 
Randomization 
and scripts 
X 
 
 
 
 
Patients fill 
prescription 
 
X 
 
 
 
Patients receive 
backup written 
prescription in 
sealed envelope 
 
X 
 
 
 
Pain diary and 
medication use  
 
 
X 
 
 
Return to 
baseline 
function 
assessment  
 
 
X 
 
 
Post-operative 
satisfaction 
survey 
 
 
 
 
X 
Remaining 
medication 
count 
 
 
 
 
X 
Patient 
reimbursement 
(parking and 
incentive – total 
$35) 
 
 
 
 
X 
 
 
 
 

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References: 
1. 
The Opioid Epidemic: By the Numbers. [Website].  http://www.hhs.gov/sites/default/files/Factsheet-opioids-
061516.pdf. Accessed October 19, 2016. 
2. 
Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: a retrospective 
analysis of the past 50 years. JAMA Psychiatry. 2014;71(7):821-826. 
3. 
Combatting The Opioid Epidemic: A Review of Anti-Abuse Efforts By Federal Authorities and Private Insurers. In. 
Committee on Homeland Security and Government Affairs Permanent Sub-Committee on Investigations. 
4. 
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;172(5):425-430. 
5. 
Bates C, Laciak R, Southwick A, Bishoff J. Overprescription of postoperative narcotics: a look at postoperative 
pain medication delivery, consumption and disposal in urological practice. J Urol. 2011;185(2):551-555. 
6. 
Swenson CW, Kelley AS, Fenner DE, Berger MB. Outpatient Narcotic Use After Minimally Invasive Urogynecologic 
Surgery. Female Pelvic Med Reconstr Surg. 2016;22(5):377-381. 
7. 
Sullivan M, Biship S, Pivik J. The pain catastrophizing scale: development and validation. Psychol Assess. 
1995;7(4):524-532.