Clinical trial NCT03088826
Conditions: Pain Management
Sponsor: Antonios Likourezos
Start date: 2017-08-18; Completion date: 2020-12-22
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Oxycodone and Hydrocodone are the most commonly used oral opioid analgesics in the emergency department and in outpatient settings. Both medications have a very high potential for abuse due to the prominence of the euphoric effect (abuse liability) and relative lack of "bad "or "negative" effects (likeability). The highly addictive properties of these medications lead to recurrent ED visits for repetitive dosing and prescribing that may lead to abuse, misuse, development of dependence and addiction, and, most importantly, death due to overdose. In contrast, several research papers demonstrated that administration of MSIR results in similar analgesic efficacy to Oxycodone and Hydrocodone but with significantly less euphoric and rewarding associated effects. In addition, consumption of large doses of MSIR leads to dysphoria, vomiting and sedation ("negative effects"). To the investigators' knowledge, there are no randomized controlled trials in the ED that directly compared analgesic efficacy of MSIR to Percocet

Detailed description:
The investigators' 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.

This study will be a double-blind randomized clinical trial evaluation analgesic efficacy of orally administered MISIR+acetaminophen in comparison to Oxycodone+acetaminophen for treating pain. Patients will be enrolled from a single ED in a tertiary academic center.

Patients based on inclusion criteria will be randomized to receive either 1 tablet of 15mg PO morphine sulfate immediate release combined with 650mg of Acetaminophen or 1 tablet 10mg Oxycodone combined with 650 mg Acetaminophen. All drugs will be crushed and given to the subjects in blinded fashion. Patients, physicians, nurses and research assistants will be blinded to drug assignment throughout the study. Medication will be prepared by on site pharmacist.

Pain will be reassessed at both 30 minutes, 45 minutes and 1 hour with the primary outcome of reduction in pain score by 1.3 points at 60 minutes. Assuming a 1.7 pain difference is minimally significant clinically with standard deviation of 3.0 (based on a previous study of morphine analgesia), a minimum of 50 patients per group will be needed for 80% power with alpha equal to 0.05.

Secondary outcomes will include any reported adverse effects; the requirement of additional analgesia.

Generalized likability and chance of repeated use will be reported by using a visual analogue scale with following 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.

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. Statistical analyses will be conducted by the research manager and the hospital senior biostatistician who will be independent of all data collection.

Arms: arm 1: The patients in this group will receive 1 tablet 15mg PO morphine sulfate immediate release combined with 650mg of Acetaminophen arm 2: The patients in this group will receive 1 tablet 10mg Oxycodone combined with 650mg of Acetaminophen
Interventions: intervention 1: Morphine Sulfate intervention 2: Oxycodone intervention 3: Acetaminophen
Intervention descriptions: intervention 1: 15mg PO morphine sulfate intervention 2: 10mg Oxycodone intervention 3: 650 mg Acetaminophen

Protocol documents:
Prot_SAP_000.pdf: 
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 
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