Comparison of Analgesic Efficacy of Morphine Sulfate Immediate Release (MSIR)/Acetaminophen vs. Oxycodone/Acetaminophen (Percocet) for Acute Pain in Emergency Department Patients
Phase: PHASE2
Conditions: Pain Management
Sponsor: Antonios Likourezos

Maimonides Medical Center Protocol  12/22/16 
TITLE: Comparison of Analgesic Efficacy of Morphine Sulfate Immediate Release 
(MSIR)/Acetaminophen  vs. Oxycodone/Acetaminophen (Percocet) for Acute Pain in 
Emergency Department Patients 
 
 
Unique Protocol ID: 2017-01-05 
 
 
Identifier #: NCT03088826 
 
 
Document Date:  December 22, 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Maimonides Medical Center Protocol  12/22/16 
Introduction: The non-medical use of prescription opioids is a major public health crisis in the 
United States. In 2014, a total of 10.3 million persons reported using prescription opioids non-
medically (i.e. using medications that were not prescribed for them or were taken only for the 
experience or feeling that they produced). In 2014, U.S. retail pharmacies dispensed 245 million 
prescriptions for opioid analgesics, which is 4 times higher when compared to 1999. Emergency 
department visits involving misuse or abuse of prescription opioids increased 153% between 
2004 and 2011, and admissions to substance-abuse treatment programs linked to prescription 
opioids more than quadrupled between 2002 and 2012. More troubling is that between 2000 and 
2014 the rates of death from prescription-opioid overdose nearly quadrupled (from 1.5 to 5.9 
deaths per 100,000 persons). The pattern of nonmedical use of prescription opioids varies, from 
infrequent use once or twice per year to daily or compulsive heavy use and addiction. A key 
underlying characteristic of the epidemic is the association between the increasing rate of opioid 
prescribing and increasing opioid-related morbidity and mortality. Oxycodone is the most 
commonly prescribed opioid in the ED and it has the highest rates of abuse, misuse, diversion 
and fatalities related to overdose. Moreover, it has been shown that a single opioid prescription 
from the ED has been associated with subsequent opioid abuse. 
 
This public health crisis calls for immediate interventions to identify safe and effective ways to 
control pain. One potentially powerful safety intervention is to identify an opioid that is effective 
for managing pain in the ED while at the same time having the least potential for recreational 
abuse, misuse and diversion. Therefore, our project is designed to investigate analgesic efficacy 
of Morphine Sulfate Immediate Release Tablets (MSIR) and consider its use in the ED as the 
alternative to commonly prescribed Oxycodone/Acetaminophen (Percocet). Our hypothesis is 
that MSIR is as effective as Percocet in treating pain in the ED and that it has far less potential 
for abuse based on the level of "likeability" and “attractiveness". The results of our investigation 
have the potential to be of great benefit to the safety of patients as well as for the education of 
providers and policy makers. By identifying a safer alternative to oxycodone, our study may 
influence opioid prescribing practices nationwide, which has the potential to reduce the 
considerable morbidity and mortality related to misuse and abuse of prescription opioids. 
Aim: We expect our study results to show that Morphine Sulfate Immediate Release (MSIR) 
possesses similar analgesic efficacy in comparison to Percocet in adult ED patients presenting 
with moderate to severe acute pain. The magnitude of the national opioid health crisis has 
reached unprecedented levels and our faculty and patients frequently express concern about what 
is being prescribed to them in the ED. Frequently, patients raise questions about the safety of 
prescribed analgesics and demonstrate significant fears about developing addiction. It is not 
uncommon to hear patients complain about receiving pain medications that induce a high feeling 
of drunkenness and euphoria. Patients present to the ED with an expectation that physicians can 
manage their pain without prescribing medications that are highly addictive. The goal of our 
project is to investigate if Morphine Sulfate Immediate Release combined with Acetaminophen 
can serve as an opioid analgesic alternative to Oxycodone combined with acetaminophen. 
Oxycodone, the active opioid ingredient in Percocet, is both the most widely prescribed and the 
most diverted and misused oral opioid, and it is responsible for more overdose related deaths 
than any prescription opioid. We believe that if we prove our hypothesis we will increase safety 

Maimonides Medical Center Protocol  12/22/16 
for all our patients who require opioid prescriptions by reducing the likelihood of misuse and 
abuse, which has the potential to make an impact nationwide by influencing future prescribing 
practices, thereby helping to address the opioid epidemic with safer alternatives to current 
practice standards. 
Hypothesis: Is there a difference in the analgesic efficacy between oral analgesics Oxycodone 
combined with acetaminophen versus MSIR combined with acetaminophen for acute pain in the 
in ED setting? 
 
Our hypothesis is that MSIR coupled with acetaminophen will have similar if not better 
analgesic efficacy at 30 minutes and 1 hour than oxycodone coupled with acetaminophen for 
acute painful conditions in the emergency department. 
 
To compare the analgesic efficacy of two oral opioid analgesics potentially used in the inpatient 
emergency department setting to change the practices of emergency department physicians. The 
goal being to provide an alternate oral analgesic option and increase utilization of MSIR in a 
patient with acute pain. As there is a reported decreased likability in MSIR, the option of using 
MSIR in the ED may lead to decrease drug seeking and abuse if proven to have equal analgesia 
to Percocet. 
Study Design: We will conduct a double-blind, randomized, clinical trial comparing analgesic 
efficacy of MSIR and Percocet in the ED for adult patients presenting with moderate-to-severe 
pain. The study site is a 711-bed community teaching hospital with a Level 1 trauma center and 
an annual ED census of greater than 120,000 visits. Three research coordinators will be assigned 
to screen and enroll patients. All participants will be randomized to receive 15mg PO morphine 
sulfate immediate release combined with 650mg of Acetaminophen or 1 tablet 10mg Oxycodone 
combined with 650 mg Acetaminophen. Patients, physicians, nurses and research assistants will 
be blinded to drug assignment throughout the study. Medications will be prepared by the ED 
pharmacist. 
 
The study enrollment will proceed as follows. The study team will screen for eligible patients 
from 8 am to 8pm from Monday to Friday. After being evaluated by the treating adult ED 
physician, each patient will be approached by a member of the research team (other than the 
pharmacists or research manager) for assessment of eligibility criteria and acquisition of written 
informed consent and HIPAA authorization. To assess pain, we will use an 11-point Numerical 
Pain Rating Scale to evaluate the analgesic effectiveness of each medication. 
To assess "likeability" a Visual Analog Scale Questions will be used to evaluate the severity of 
the patient’s subjective effects. (Table 1) 
 
 
 
 

Maimonides Medical Center Protocol  12/22/16 
TABLE 1 
Questions: 
“Do you feel any DRUG EFFECT?” 
“Do you LIKE the drug?” 
“How HIGH are you?” 
“Does the drug have any GOOD EFFECTS?” 
“Does the drug have any BAD EFFECTS?” 
“How much do you DESIRE the medication?” 
" Does the drug make you have UNPLEASANT THOUGHTS?” 
“Does the drug make you have UNPLEASANT BODILY SENSATIONS?” 
“Does the drug make you feel IRRITATED?” 
“Does the drug make it DIFFICULT TO CONCENTRATE?” 
 
The patients will respond by positioning an arrow along 
a 100-point line labeled with “not at all” at one end and “extremely” at the other 
 
ED pharmacy investigators will maintain the randomization list which will be generated prior to 
commencement of the study, prepare the medication, and deliver it in a blinded manner to the 
nurse caring for the study participant. The study coordinators will screen for patients who qualify 
to be in the study. Patients will be included if upon evaluation by their treating physicians they 
warrant prescribing of oral narcotic analgesia. Painful conditions may include but are not limited 
to acute traumatic musculoskeletal pain including fracture and dislocations, renal colic and 
dental pain. 
 
Patients’ pain intensity will be assessed at 30, 45 and 60 minutes. The clinically significant pain 
outcome is reduction in pain score at 60 minutes. Secondary outcomes will include the rate of 
reportable adverse effects and the requirement of additional analgesia. 
 
The minimum clinically significant difference in generalized likability and chance for repeated 
use is by 2 mm for each question by using VAS. 
Statistical Analyses: Data will be analyzed by intention to treat and will include frequency 
distributions, and Student’s T-test to assess a difference in pain scores and vital signs. The chi-
square test will assess the presence or absence of side effects between the two groups. P<.05 will 
denote statistical significant difference between the groups.  
 
 
 
 
 

Maimonides Medical Center Protocol  12/22/16 
References: 
1. Phillips DM. JCAHO pain management standards are unveiled. Joint Commission 278 on 
Accreditation of Healthcare Organizations. JAMA 2000;284:428–9. N 279 
2. Schwartz RK, Soumerai SB, Avorn J. Physician motivations for nonscientific 280 drug 
prescribing. Soc Sci Med 1989;28:577–82. 281 
3. Maxwell JC. The prescription drug epidemic in the United States: a perfect storm. 282 Drug 
Alcohol Rev 2011;30:264–70. N 283 
4. Manchikanti L, Helm S 2nd, Fellows B, et al. Opioid epidemic in the United 284 States. Pain 
Physician 2012;15(3 Suppl):ES9–38. N 285 
5. Centers for Disease Control and Prevention. Prescription opioid overdose data. 286 
http://www.cdc.gov/drugoverdose/data/overdose.html. Accessed August 6, 1016. 287 
6. Beaudoin FL, Merchant RC, Janicki A, McKaig DM, Babu KM. Preventing 288 iatrogenic 
overdose: a review of in-emergency department opioid-related adverse 289 drug events and 
medication errors. Ann Emerg Med 2015; 65;423-31. 290 
7. Gulseth MP, Meisel S, Meisel M. Increasing the safety of analgesia use in a 291 community 
hospital. Am J Health Syst Pharm 2004; 61:1143-6. 292 
8. Neil K, Marcil A, Kosar L, et al. Retrospective analysis of opioid medication 293 incidents 
requiring the administration of naloxone. Can J Hosp Pharm 2013; 66: 294 280-288. 295 
9. Mazer-Amirshahi M, Mullins PM, Rasooly I, van den Anker J, Pines JM. Rising 296 opioid 
prescribing in adult U.S. emergency department visits:2001-2010. Acad 297 Emerg Med 2014; 
21:236-43. 298 
10. Mazer-Amirshahi M, Dewey K, Mullins PM, van den Anker J, Pines JM, Perrone 299 J, 
Nelson L. Trends in opioid analgesic use for headaches in U.S. emergency 300 departments. Am 
J Emerg Med 2014; 32:1068-73. 
11. Butler MM, Ancona RM, Beauchamp GA, et al. Emergency department 308 prescription 
opioids as an initial exposure preceding addiction. Ann Emerg Med 309 2016;68:202-8 
12. Atluri S, Sudarshan G, Manchikanti L, et al. Assessment of the trends in medical 442 use and 
misuse of opioid analgesics from 2004 to 2011. Pain Physician 443 2014;17:E119-28. 
13. Dasgupta N, Freifeld C, Brownstein JS, Menone CM, et al. Crowdsourcing black 446 market 
prices for prescription opioids. J Med Internet Res 2013;16:e178. 
14. Wightman R, Perrone J, Portelli I, Nelson L. Likeability and abuse liability of 453 commonly 
prescribed opioids. J Med Toxicol 2012;8:335-40. 
15. Jasinski DR. Assessment of the abuse potentiality of morphine-like drugs 456 (methods used 
in man).In: Martin WR,Drug Addiction I, Springer Publishing, 457 1977. 
http://link.springer.com/chapter/10.1007/978-3-642-66612-4_4. 
16. Bickel WK, Bigelow GE, Preston KL, Liebson IA. Opioid drug discrimination in 460 
humans: stability, specificity and relation to self-reported drug effect. J Pharmacol 461 Exp Ther 
1989;251:1053-63.