Clinical trial NCT03588910
Conditions: Surgery
Keywords: ambulatory narcotics opioids postoperative gynecology laparoscopy pain surgery
Sponsor: Montefiore Medical Center
Start date: 2018-08-08; Completion date: 2019-08-04
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Currently there is a nationwide epidemic in opioid abuse and overdose deaths. While the opioid epidemic is multi-factorial one major source of excess opioids may be over-prescribing in the post-operative period. There is wide variation in the prescribing practices for post-operative pain control and there is no standard of care for pain control after minor laparoscopic surgery in general or after gynecologic laparoscopy. There is also evidence to show that on average half of the opioids prescribed are unused by the patient. The aim of the study is to evaluate two opioid prescription regimens.

Detailed description:
This will be a randomized controlled study enrolling participants scheduled for outpatient minor laparoscopic gynecologic surgery. This is a two arm study consisting of 60 subjects in each arm. The participants will be randomized at the time of enrollment. We will use computer generated blocks of four participants. Both arms of participants will receive the same non-narcotic pain medication prescriptions which will include fifty tablets of acetaminophen 500mg (1-2 tablets every 6 hours as needed) and twenty-five tablets ibuprofen 600mg (1 tablet every 6 hours as needed). The arms will only differ in the number of tablets of oxycodone prescribed. In one arm (experimental) subjects will receive five tablets of oxycodone 5mg (1 tablet every 6 hours as needed) and the other arm (comparator) ten tablets of oxycodone 5mg (1 tablet every 6 hours as needed). Both prescription regimens are within the range of normal clinical practice for post-operative pain control.

The participants will receive a telephone call by administrative staff, who is not directly involved in the participants care or data collection for the study subjects, on postoperative day 1 and 7. The participants will all be scheduled for a 2- week post-operative follow up with the surgeon in the office. The primary outcome to be assessed will be number of opioids used by the participants at 24 hours and 7 days post-operative. The primary hypothesis is that participants prescribed only 5 tabs of oxycodone will not require more medication. The secondary hypothesis is that the pain scores between the two groups will not be different. The other variables being studied include the following: having had a post-operative bowel movement, presence of nausea, number of ibuprofen, acetaminophen tablets remaining, calls to the office prior to the follow up visit for pain issues, and urgent or emergency department visits for pain issues. These assessments will be asked during the brief telephone calls and also at the postoperative visit.

All participants will be given the clinic phone number and advised to call with any questions or clinical concerns. The participants will be advised if possible to return to a Montefiore Emergency Department or gynecologic provider in case of an urgent issue prior to the 2 week postoperative visit, as opposed to an outside facility.

Arms: arm 1: Participants will receive a prescription for 10 tablets of 5 mg oxycodone (1 tablet every 6 hours as needed) as well as 50 tablets of acetaminophen 500mg (1-2 tablets every 6 hours as needed) and 25 tablets ibuprofen 600mg (1tablet every 6 hours as needed). arm 2: Participants will receive 5 tablets of 5mg oxycodone as well as 50 tablets of acetaminophen 500mg (1-2 tablets every 6 hours as needed) and 25 tablets ibuprofen 600mg (1tablet every 6 hours as needed).
Interventions: intervention 1: Acetaminophen intervention 2: Ibuprofen 600 mg intervention 3: Oxycodone
Intervention descriptions: intervention 1: 50 tablets of acetaminophen 500mg (1-2 tablets every 6 hours as needed) intervention 2: 25 tablets ibuprofen 600mg (1tablet every 6 hours as needed) intervention 3: The number of tablets of oxycodone prescribed is the only difference between the two arms.

Protocol documents:
Prot_SAP_000.pdf: 
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Ambulatory Gynecologic Surgery: Finding the Optimal Opioid Prescription
Introduction:
Currently there is a nationwide epidemic in opioid abuse and overdose deaths. While the opioid 
epidemic is multi-factorial, one major source of excess opioids may be over-prescribing in the 
post-operative period. There is wide variation in the prescribing practices for post-operative pain 
control and there is no standard of care for pain control after minor laparoscopic surgery in 
general or after laparoscopic gynecologic surgery. There is also evidence to show that less than 
half of the opioids prescribed are used by the patient (Hill 2017, As-Sanie 2017) and that many 
patients feel they are prescribed too many opioids (Hota 2017). We are aiming to examine how 
the number of narcotic pills prescribed post operatively may affect the patient experience in the 
recovery period.  
Study Design:
This will be a randomized controlled study enrolling patients scheduled for outpatient minor 
laparoscopic gynecologic surgery. Enrollment will start after IRB approval. We aim to enroll 120 
patients to be able to evaluate outcomes for 100 patients with an anticipated 10-20% dropout 
rate.  This is a two arm study consisting of 60 subjects in each arm.  The patients will be 
randomized at the time of enrollment. We will use computer generated blocks of four patients. 
Both arms of patients will receive the same non-narcotic pain medication prescriptions which 
will include 50 tablets of acetaminophen 500mg (1-2 tablets every 6 hours as needed) and 25 
tablets ibuprofen 600mg (1tablet every 6 hours as needed). The standard arm will receive a 
prescription for 10 tablets of 5 mg oxycodone (1 tablet every 6 hours as needed). The 
intervention arm will be prescribed 5 tablets of 5mg oxycodone. Both of these prescription 
regimens are within the range of normal clinical practice for post-operative pain control.
Patient demographics to be studied will include age, race, parity, body mass index, insurance 
status, smoking status, medical co-morbidities and ASA classification. Other variables of interest 
include patient surgical history (number of previous abdominopelvic surgeries- total, 
laparoscopic, and open), surgeon characteristics, procedure performed and surgical findings.  
The patients will receive a telephone call by administrative staff, who is not directly involved in 
the patient care or data collection for the study subjects, on postoperative day 1 and 7.  The 
subjects will all be scheduled for a 2- week post-operative follow up with the surgeon in the 
office.  The primary outcome to be assessed will be number of opioids used by the patient at 24 
hours and 7 days post-operative. Our hypothesis is that patients prescribed only 5 tabs of 
oxycodone will not require more medication. Our secondary hypothesis is that the pain scores 
between the two groups will not be different.  The other variables being studied include the 
following:  having had a post-operative bowel movement, presence of nausea, number of 
ibuprofen, acetaminophen tablets remaining, calls to the office prior to their follow up visit for 
IRB NUMBER: 2018-8755
IRB APPROVAL DATE: 07/19/2018


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pain issues, and urgent or emergency department visits for pain issues. These assessments will be 
asked during the brief telephone calls and also at the postoperative visit.  
All patients will be given the clinic phone number and advised to call with any questions or 
clinical concerns.  They will be advised if possible to return to a Montefiore ER or GYN 
provider in case of an urgent issue prior to their 2 week postoperative visit, as opposed to an 
outside facility.  They will be counseled to bring their medical records with them to their 
postoperative visit or notify us of any such outside visit.
Study Population:
All patients presenting for outpatient laparoscopic gynecologic surgery will be assessed for 
inclusion. Exclusion criteria include: recent opioid use as determined by use in the past 3 weeks, 
and those with contraindications to receiving the study medications.   These include: 
hypersensitivity or allergy to any NSAID, aspirin, ibuprofen, acetaminophen, oxycodone, a 
history of coronary artery bypass graft, any active gastrointestinal bleeding, active 
gastrointestinal ulcer disease, advanced hepatic disease, alcoholic liver disease, coagulopathy, 
heart failure, impaired renal function (Creatinine >1.2), G6PD deficiency, respiratory depression, 
or hypotension.
Clinicians will identify patients during pre-operative evaluation and will approach to inquire if 
patients are interested. The study team will consent patients pre-operatively for enrollment. 
There will be no exclusion of non-English language speakers; the Montefiore telephonic 
interpreter services will be utilized for translation services.
Risks:
This study will use post-operative pain control regimens that are within the standard of care, 
therefore the intervention itself does not pose additional risk to the patient. Medications will 
be prescribed as clinically necessary and will not be withheld from the patient as needed.  
As is routinely done for all post surgical patients, patients will be counseled to take the pain 
medications as prescribed and not take additional over the counter pain medications without 
speaking to their provider first.  Patients will be asked during the phone surveys and at the 
follow up visit if additional medications were taken for pain control.  All appropriate 
measures will be taken to prevent any breach in confidentiality of protected health 
information. Some physicians typically call their patients on the first post-operative day as 
well; hence this is not a significant change in clinical practice.  
Benefits:
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Study benefits are to future patients undergoing ambulatory laparoscopic surgery to find the best 
modalities to treat post-operative pain. The benefits are also to society at large if we are able to 
decrease the excess opioids contributing to the opioid epidemic.
Sample Size Calculation:
The primary outcome will be the number of opioids used by the patients. With N=50 sample size 
for each group after dropout, standardize effect sizes (i.e., mean difference in SD units between 
groups) of the primary outcome greater than 0.6 will be detected with >80% power at a two-
sided significance level of 0.05 with application of a Mann-Whitney test.
Data Analysis:
Software use for analysis will be based on the discretion of the statistician.  A p-value of <0.5 
will be considered to be significant. The chi-squared test and the Fisher’s exact test will be used 
to compare categorical variables. The Mann-Whitney U test will be used to analyze continuous 
variables.  The treatment arms will be compared to assess for any significant differences in 
baseline characteristics including demographic variables, surgical data, and surgeon 
characteristics.  These differences will be controlled for in a secondary analysis.  
Data Safety and Monitoring Plan:
Data quality control and database management:
Data collected for study use will be maintained in a locked office on a password protected 
computer and accessible only to study investigators. Patient identifiers will be kept separate from 
the data collection sheet on a password protected computer and accessible only to study 
investigators.  
Patient cases will be continually reviewed on a bi-weekly basis by the PI. If any safety issues 
arise they will be addressed by the study team. The patients will be in continuous care of the 
physicians for the weeks after surgery should any issues arise. 
References:
Thomazeau J, Rouquette A, Martinez V, Rabuel C, Prince N, Laplanche JL, Nizard R, Bergmann 
JF, Perrot S, Lloret-Linares C. Acute pain factors predictive of post-operative pain and opioid 
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De Oliveira GS Jr, Ahmad S, Fitzgerald PC, Marcus RJ, Altman CS, Panjwani AS, McCarthy 
RJ. Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of 
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https://www.cdc.gov/drugoverdose/data/index.html
IRB NUMBER: 2018-8755
IRB APPROVAL DATE: 07/19/2018