Clinical trial NCT02455518
Conditions: Pain
Keywords: pain
Sponsor: Montefiore Medical Center
Start date: 2015-07-01; Completion date: 2017-10-04
Enrollment: 416 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to perform a randomized, double blind 4-arm clinical trial of the comparative efficacy of 4 oral analgesics in the initial management of acute musculoskeletal extremity pain presenting to the ED.

Detailed description:
To perform a randomized, double blind 4-arm clinical trial of the comparative efficacy of 4 oral analgesics in the initial management of acute musculoskeletal extremity pain presenting to the ED. The 4 groups are as follows:

1. Oxycodone/acetaminophen (5/325)
2. Hydrocodone/acetaminophen (5/325)
3. Codeine/acetaminophen (30/300)
4. Ibuprofen/acetaminophen (400/1000)

Arms: arm 1: Oxycodone/acetaminophen (5 mg/325 mg) arm 2: Hydrocodone/acetaminophen (5 mg/300 mg) arm 3: Codeine/acetaminophen (30 mg/300 mg) arm 4: Ibuprofen/acetaminophen (400 mg/1000 mg)
Interventions: intervention 1: Oxycodone/acetaminophen intervention 2: Hydrocodone/acetaminophen intervention 3: Codeine/acetaminophen intervention 4: Ibuprofen/acetaminophen
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents:
Prot_SAP_000.pdf: 
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Title:  Comparative efficacy of 4 oral analgesics for the initial management of acute musculoskeletal 
extremity pain 
 
Investigators: Andrew Chang, M.D; David Esses, M.D; E. John Gallagher, M.D. 
 
 
Objective:  To perform a randomized, double blind 4-arm clinical trial of the 
comparative efficacy of 4 oral analgesics in the initial management of acute 
musculoskeletalextremity pain presenting to the ED.   
 
Introduction 
 
According to a recent study, over 44 million emergency department (ED) visits 
per year are for a chief complaint related to pain. Approximately 29%, or 12.8 million, of 
these visits result in a prescription for an analgesic.1  Yet, there are only a handful of 
studies that compare the efficacy of acute pain management of the most commonly 
prescribed oral analgesics.2-7 
The Cochrane Collaboration has produced several reviews describing the 
effectiveness of codeine, both with and without acetaminophen, as well as a review of the 
efficacy of oxycodone alone or in combination with acetaminophen.  Indirect 
comparisons over a period of 4-6 hours demonstrated greater efficacy with oxycodone 
compared to codeine.8-10Most of the studies included in the reviews were postoperative 
dental studies utilizing extraction of the third molar as the pain model.  There are no 
Cochrane reviews that describe the efficacy of hydrocodone.   
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Two randomized controlled trials were found comparing hydrocodone and 
codeine for chronic pain.  Rodriguez et. al. found no significant difference in either 
analgesia or incidence of side effects in a study of 121 patients using 5 mg of 
hydrocodone vs. 30 mg of codeine, both in combination with 500 mg of 
acetaminophen.11Palangio et al. in a three armed study design with 469 patients, found 
greater analgesia in the 15/400 mg hydrocodone/ibuprofen group compared to the 60/600 
mg of codeine/acetaminophen.6 
We have conducted three randomized clinical trials of oral opioids for patients 
discharged from the ED following presentation for acute musculoskeletal pain.  The first 
compared hydrocodone/acetaminophen against codeine/acetaminophen and found no 
difference in change in pain intensity when patients were contacted 24-hours post-
discharge.12  The second compared oxycodone/acetaminophen against 
codeine/acetaminophen and again found no difference at 24 hours (manuscript is in 
“revise and resubmit” status).The third trial compared oxycodone/acetaminophen against 
hydrocodone/acetaminophen and also failed to show a difference in pain control at 24 
hours following ED discharge (preliminary and unpublished data).  The design of these 
studies differed from other studies of oral analgesics in that patients were called 24 hours 
after they left the ED, and they were asked to recall their pain intensity just prior to their 
most recent dose of pain medication and again 2 hours after ingestion of the study 
medications.  
An alternative to oral opioid analgesics combined with acetaminophen is the 
combination of non-steroidal antiinflammatory drugs (NSAIDS) and acetaminophen.  A 
review published in 2010 found the combination of various NSAIDS and acetaminophen 
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to be superior to acetaminophen alone in 17 of 20 studies.13The combination of ibuprofen 
and acetaminophen published since that review has been found to be more effective than 
each drug alone in 4 out of 5 trials of patients following dental surgery.14-17Only one 
small ED study that examined the effect of the 800 mg ibuprofen/1000 mg 
acetaminophen combination on musculoskeletal pain one hour after administration did 
not find it to be superior to either of the component drugs.18 
We could find only one direct comparison between an ibuprofen/acetaminophen 
combination and an oral opioid combination. Patients who received 400 mg ibuprofen/ 
1000 acetaminophen following extraction of a third molar had significantly less pain and 
greater pain relief in the 12 hour period after analgesic administration than patients who 
received 30 mg codeine/1000 mg acetaminophen.14 
For this proposed study, we wished to look at the comparative efficacy of a single 
dose of 4 oral analgesics given while the patient is still in the ED.  We believe this will 
enhance our understanding of these commonly prescribed oral analgesics by eliminating 
recall bias,which may have played a role in driving our prior findings comparing 
acetaminophen/codeine vs. hydrocodone/acetaminophen and oxycodone/acetaminophen 
toward the null of no difference among the 3 combination analgesics when assessed 24 
hours later.  
 
Methods 
 Design: 
 
This will be a randomized, double blind, comparative efficacy trial of oral 
analgesics with four single-dose treatment arms:  oxycodone 5 mg/ acetaminophen 325 
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mg, hydrocodone 5mg/acetaminophen 300mg, codeine 30 mg/acetaminophen 300mg, 
and ibuprofen 400 mg/acetaminophen1000 mg.   
 
Setting: 
The study will be performed simultaneously in 2 teaching hospitalsED’s affiliated 
with the Albert Einstein College of Medicine, both located in the Bronx, approximately 5 
miles apart, with a total of 180,000 adult visits annually.  Both EDsare staffed by trained 
bilingual (Spanish and English) salaried research associates (RAs) available 24 hours a 
day/7 days a week.  The research associates receive training in the ethical and practical 
aspects of data collection and a practicum with a senior research associate.  Some of the 
RAs have been enrolling study patients for 5-10 years.  
 
Patients: 
 
Inclusion criteria: Patients age 21 to 64 years of age; complaint of acute pain of 
less than seven days duration; location of pain in one or more extremities defined as 
distal to and including the shoulder joint in the upper extremities and distal to and 
including the hip joint in the lower extremities; radiologic evaluation is planned; and 
willingness to provide NRS pain scores after discharge from the ED.   
Exclusion criteria: Inability to reach patient on patient’s cell phone while in the 
ED; past use of methadone; chronic condition requiring frequent pain management such 
as sickle cell disease, fibromyalgia, or any neuropathy; history of an adverse reaction to 
any of the study medications; opioids taken in the past 24 hours; ibuprofen or 
acetaminophen taken in past 8 hours; pregnancy by either urine or serum HCG testing; 
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breastfeeding per patient report; history of peptic ulcer disease; report of any prior use of 
recreational narcotics; medical condition that might affect metabolism of opioid 
analgesics, acetaminophen, or ibuprofen such as hepatitis, renal insufficiency or failure, 
hypo- or hyperthyroidism, Addison’s or Cushing’s disease; taking any medicine that 
might interact with one of the study medications, such as antidepressant SSRI’s or 
Tricyclics, antipsychotics, anti-malaria medications quinidine or halofantrine, 
Amiodarone or Dronedarone, diphenhydramine, celecoxib, ranitidine, cimetidine, 
ritanovir, terbinafine, or St John’s Wort.   
 
Measures 
Pain intensity will be assessed by an 11-point numeric rating scale (NRS) where 0 
indicates no pain, 10 indicates worst possible pain.  The primary endpoint will be the 
difference between NRS pain between the time immediately prior to ingestion of the 
study medication and 2 hours later. Secondary outcomes include NRS scores at 1 
hourpain based on a 4-point Likert scale (none, mild, moderate, severe), and overall 
satisfaction with the pain medication using a 4-point Likert scale:  very satisfied, 
satisfied, unsatisfied, or very unsatisfied with the study medication.  Other outcomes 
include the incidence of side effects (nausea, vomiting, itchiness, rash,drowsiness, or 
confusion). 
Baseline information will be obtained from the patient including demographic 
characteristics and a listing of all over-the-counter, topical, and prescribed analgesics 
taken in the 24 hours prior to enrollment.  Diagnosis, rescue medication, and any other 
treatment received will be recorded, such as application of ice and splints.   
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Protocol: 
Patients will be referred to the study by the patient’s provider.  The treating 
attending will confirm that the patient has met enrollment criteria and assess whether the 
patient has capacity to provide informed consent.  RAs will describe the study in detail 
and obtain informed consent.  Following randomization all patients will have their pain 
scores assessed immediately before administration of the study drug and 1 hour later 
while in the ED.  If the patient remains in the ED, additional NRS pain scores and 
incidence of side effects will be assessed at 2 hours post-baseline.  Patients who are 
discharged prior to 2 hours will be called at the appropriate time to obtain their pain 
scores.  Since radiologic imaging is required for study entry, it is anticipated that the 
majority of patients will have most of their pain scores assessed while still in the ED.  In 
our 3 prior oral opioid studies, more than 95% of study subjects were reached by phone at 
24 hours.  Thus, we do not anticipate any difficulty in being able to contact patients up to 
2 hours after study medication is administered.   
 
An on-line random number generator (www.randomization.com) will be used to 
allocate patients in blocks of 8to one of four experimental groups: oxycodone 
5mg/acetaminophen 325mg, hydrocodone 5mg/acetaminophen 300mg, codeine 
30mg/acetaminophen 300mg, or ibuprofen 400mg/acetaminophen 1000 mg. The opioid 
and acetaminophen combinations were selected to reflect commonly used analgesics for 
musculoskeletal pain.  The choice of dose for the ibuprofen/acetaminophen combination 
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is based on a recently published study performed in the ED18and our desire to not miss an 
analgesic effect by administering a sub-therapeutic dose. 
The research pharmacist will ensure proper allocation concealment by inserting 
each study medication combination into 3 identical unmarked opaque gel capsules, filling 
any void with small quantities of lactose to equalize weight.  The capsules will be placed 
in numbered packetsby the research pharmacist working in an area distant from and 
inaccessible to ED staff.  Each packet will have a sealed opaque envelope stapled to it 
that indicates what medication it contains so that the assignment is readily available if 
this information is needed clinically due to a serious adverse reaction.   The RAs will 
retrievethe packets in sequential order and the nurse will dispense the medication to the 
patient. Patients, providers, and RAs will be blinded to study allocation.   
Patients who require rescue medications will receive oxycodone 5 mg (without 
acetaminophen).  This will be determined subjectively (i.e. if the patient requests 
additional pain medication or the treating physician decides that additional pain 
medication is needed).  Discharge medications will be administered by the treating 
physician as per his/her usual care.  
 
 
 
Data Collection and Processing 
Data will be collected on a standardized data collection instrument in REDCAP, 
an electronic data capture system. The PI will review the data collected and informed 
consent documentsweekly for accuracy and completeness.   
 
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Data analysis 
The primary data analysis will be a one-way analysis of variance testing the null 
hypothesis that there are no differences between the effect of the medications on mean 
change in pain from baseline to 2 hours post-baseline with a significance level of 0.05.  If 
there is evidence to reject the null hypothesis we will conduct the set of t-tests comparing 
all pairwise mean differences in pain. The Bonferroni method will be used to adjust the 
overall significance level of 0.05 in order to account for multiple comparisons.  The data 
will be presented as the difference between each pair of means and the set of 95% 
simultaneous Bonferroni CIs around the differences. SPSS version 22 (Chicago, IL.) will 
be used to conduct all data analyses.  Data will be stored in an identified format in the 
event that a metaanalysis of studies is performed in the future. 
 
Sample Size Calculation 
The following parameters were used to calculate the sample size:  an overall 2-
sided significance level of 0.05 (0.008 for each t-test using the Bonferroni correction), 
power of 80%, 1.3 NRS unit or greater difference in change in pain between groups 
based on a standard definition of the minimal clinically significant difference in pain, and 
a within group standard deviation of 2.6 based on estimates of variability of change in 
pain in response to oral opioid analgesics.  Using these parameters 100 patients are 
needed in each group for a total of 400 patients.   We will plan to continue to enroll 
patients until we have 400 patients with usable data (not missing primary outcome or 
other critical data points).  Based on past experience we estimate not needing more than 
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20 additional subjects to order to reach our target sample size of 400 patients.  We used 
nQuery Advisor 7.0 (Los Angeles, CA) to calculate the sample size.   
 
Data safety and monitoring 
Data monitoring committee and interim analysis.This committee will be composed of Dr. 
Polly Bijur, PhD, a statistician and epidemiologist, and Dr. Benjamin Friedman who will 
meet quarterly tomonitor adverse events, recruitment, and enrollmentAn interim analysis, 
which will be approved by the DSMC prior to randomization, will be conducted after 200 
subjects (50 in each treatment arm) with analyzable data have been enrolled. The purpose 
of the interim analysis is to identify one or more treatments that are clearly inferior or 
superior to the others. A clinically important difference in change in pain has been 
defined as 2 units or more on an NRS scale or 20 mm or more on a VAS score.  We will 
examine the point estimates of the change in pain.  If one or more arms has a mean 
decrease in pain that is at least 2 NRS units less than in other arms, that arm(s) will be 
discontinued regardless of statistical significance.   For example, if group A has mean 
pain scores that decrease from 8 NRS units to 4 NRS units over time, and group B has 
mean pain scores that decrease from 8 NRS units to 6 NRS units, we will discontinue 
treatment B.  If one group is clearly superior by this much the trial will be terminated.   
Conclusion 
 
This randomized, double-blind clinical trial is expected to further our 
understanding of the relative efficacy of 4 commonly used oral analgesics for acute 
musculoskeletal extremity pain.  In particular, we are interested in comparing the efficacy 
of high-dose ibuprofen/acetaminophen with traditional combinations of opioids and 
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acetaminophen. The results of these studies are intended to improve the emergency 
medicine physician’s ability to manage acute extremity pain in the emergency 
department. 
 
 
 
 
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References 
 
1. 
Pletcher MJ, Kertesz SG, Kohn MA, Gonzales R. Trends in opioid prescribing 
by race/ethnicity for patients seeking care in US emergency departments. JAMA : the 
journal of the American Medical Association 2008;299:70-8. 
2. 
Charney RL, Yan Y, Schootman M, Kennedy RM, Luhmann JD. Oxycodone 
versus codeine for triage pain in children with suspected forearm fracture: a 
randomized controlled trial. Pediatric emergency care 2008;24:595-600. 
3. 
Forbes JA, Bates JA, Edquist IA, et al. Evaluation of two opioid-acetaminophen 
combinations and placebo in postoperative oral surgery pain. Pharmacotherapy 
1994;14:139-46. 
4. 
Litkowski LJ, Christensen SE, Adamson DN, Van Dyke T, Han SH, Newman KB. 
Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg compared 
with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 
mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: 
a randomized, double-blind, placebo-controlled, single-dose, parallel-group study in 
a dental pain model. Clinical therapeutics 2005;27:418-29. 
5. 
Palangio M, Morris E, Doyle RT, Jr., Dornseif BE, Valente TJ. Combination 
hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in 
the treatment of moderate or severe acute low back pain. Clinical therapeutics 
2002;24:87-99. 
6. 
Palangio M, Wideman GL, Keffer M, et al. Combination hydrocodone and 
ibuprofen versus combination oxycodone and acetaminophen in the treatment of 
postoperative obstetric or gynecologic pain. Clinical therapeutics 2000;22:600-12. 
7. 
Turturro MA, Paris PM, Yealy DM, Menegazzi JJ. Hydrocodone versus codeine 
in acute musculoskeletal pain. Annals of emergency medicine 1991;20:1100-3. 
8. 
Derry S, Moore RA, McQuay HJ. Single dose oral codeine, as a single agent, for 
acute postoperative pain in adults. The Cochrane database of systematic reviews 
2010:CD008099. 
9. 
Gaskell H, Derry S, Moore RA, McQuay HJ. Single dose oral oxycodone and 
oxycodone plus paracetamol (acetaminophen) for acute postoperative pain in 
adults. The Cochrane database of systematic reviews 2009:CD002763. 
10. 
Toms L, Derry S, Moore RA, McQuay HJ. Single dose oral paracetamol 
(acetaminophen) with codeine for postoperative pain in adults. The Cochrane 
database of systematic reviews 2009:CD001547. 
11. 
Rodriguez RF, Castillo JM, Del Pilar Castillo M, et al. Codeine/acetaminophen 
and hydrocodone/acetaminophen combination tablets for the management of 
chronic cancer pain in adults: a 23-day, prospective, double-blind, randomized, 
parallel-group study. Clinical therapeutics 2007;29:581-7. 
12. 
Chang AK, Bijur PE, Munjal KG, John Gallagher E. Randomized clinical trial of 
hydrocodone/acetaminophen versus codeine/acetaminophen in the treatment of 
acute extremity pain after emergency department discharge. Academic emergency 
medicine : official journal of the Society for Academic Emergency Medicine 
2014;21:227-35. 
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13. 
Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol 
(acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative 
systematic review of analgesic efficacy for acute postoperative pain. Anesthesia and 
analgesia 2010;110:1170-9. 
14. 
Daniels SE, Goulder MA, Aspley S, Reader S. A randomised, five-parallel-
group, placebo-controlled trial comparing the efficacy and tolerability of analgesic 
combinations including a novel single-tablet combination of ibuprofen/paracetamol 
for postoperative dental pain. Pain 2011;152:632-42. 
15. 
Mehlisch DR, Aspley S, Daniels SE, Bandy DP. Comparison of the analgesic 
efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol 
alone in the management of moderate to severe acute postoperative dental pain in 
adolescents and adults: a randomized, double-blind, placebo-controlled, parallel-
group, single-dose, two-center, modified factorial study. Clinical therapeutics 
2010;32:882-95. 
16. 
Mehlisch DR, Aspley S, Daniels SE, Southerden KA, Christensen KS. A single-
tablet fixed-dose combination of racemic ibuprofen/paracetamol in the 
management of moderate to severe postoperative dental pain in adult and 
adolescent patients: a multicenter, two-stage, randomized, double-blind, parallel-
group, placebo-controlled, factorial study. Clinical therapeutics 2010;32:1033-49. 
17. 
Merry AF, Gibbs RD, Edwards J, et al. Combined acetaminophen and 
ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial. 
British journal of anaesthesia 2010;104:80-8. 
18. 
Bondarsky EE, Domingo AT, Matuza NM, Taylor MB, Thode HC, Jr., Singer AJ. 
Ibuprofen vs acetaminophen vs their combination in the relief of musculoskeletal 
pain in the ED: a randomized, controlled trial. The American journal of emergency 
medicine 2013;31:1357-60. 
 
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ICF_001.pdf: 
Einstein IRB Greater Than Minimal Risk Template v. 12/12/2014 
Page 1 of 5 
ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY 
MONTEFIORE MEDICAL CENTER 
 
DOCUMENTATION OF INFORMED CONSENT AND HIPAA AUTHORIZATION 
 
Introduction 
You are being asked to participate in a research study called “Comparative efficacy of 4 oral 
analgesics for the initial management of acute musculoskeletal extremity pain.” Your 
participation is voluntary -- it is up to you whether you would like to participate. It is fine to say 
“no” now or at any time after you have started the study. If you say “no,” your decision will not 
affect any of your rights or benefits or your access to care. 
 
The researcher in charge of this project is called 
the “Principal Investigator.” His name is Dr. 
Andrew Chang. You can reach Dr. Chang at:  
Office Address: 111 East 210th Street 
City, State Zip:  Bronx, NY 10467 
Telephone #: 718-920-6626 
For questions about the research study, or if you 
believe you have an injury, contact the Principal 
Investigator or the IRB. 
The Institutional Review Board (IRB) of 
the Albert Einstein College of Medicine 
and Montefiore Medical Center has 
approved this research study. The IRB # 
is in the stamp in the upper right hand 
corner. If you have questions regarding 
your rights as a research subject you may 
contact the IRB office at 718-430-2253 or 
by mail: 
 
Einstein IRB  
Albert Einstein College of Medicine 
1300 Morris Park Ave., Belfer Bldg #1002 
Bronx, New York 10461 
Support for this research study is provided by the 
Department of Emergency Medicine 
 
Why is this study being done?  
 
The goal of this study is to find out which, if any, of four pain medicines provides the best pain 
relief for patients who come to the emergency department with acute arm or leg injury.   
 
The four pain pills are: oxycodone/ acetaminophen (Percocet), hydrocodone/ acetaminophen 
(Vicodin), codeine/ acetaminophen (Tylenol #3) and ibuprofen/ acetaminophen (Motrin & 
Tylenol).  All four pain medications used in this study are approved by the U.S. Food and Drug 
Administration (FDA) to treat acute pain and are commonly used in the Montefiore emergency 
departments.   
 
Why am I being asked to participate?  
 
You are being asked to participate in this study because your physician plans to give you a pain 
medication to treat your acute pain and your physician thinks you need an x-ray.   
 
 
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How many people will take part in the research study? 
 
You will be one of about 400 people who will be participating in this study.  All research subjects 
will be enrolled from the Moses and Weiler adult emergency departments of Montefiore Medical 
Center.  
 
How long will I take part in this research? 
 
It will take you about 2 hours to complete this research study.  You will need to remain in the ED 
for a minimum of 1 hour after taking the study medication.  If you are discharged before 2 hours, 
we will call you at the 2 hours and ask you about your pain level.   
 
What will happen if I participate in the study?   
 
If you are eligible for the study, we will spend about 10 minutes asking you questions about your 
medical history (including medications that you take or have taken), your age, gender, and 
ethnicity and we will take your vital signs.  If you are a woman, you may not participate if you are 
pregnant or breastfeeding.  You will be asked to rate your pain on various pain scales.  We will 
then assign you by chance (like a coin toss) to the oxycodone/acetaminophen group, the 
hydrocodone/acetaminophen group, the codeine/acetaminophen group, or the 
ibuprofen/acetaminophen group.  You and the study doctor cannot choose your study group.  
You will have equal chance of being assigned to one of these 4 study groups. You will receive 3 
tablets that have been coated to prevent you, the research study doctor, the research associate 
or the nurse from knowing which of the four medicines you are receiving. However, if the study 
doctor needs to find that out in an emergency, he can do so.  If you require a rescue pain 
medication, you will receive oxycodone 5 mg, which is an opioid pain medication.  The study will 
end 2 hours after you receive the study medicine.    
 
A description of this clinical trial will be available on 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. 
 
 
 
Will I be paid for being in this research study?  
 
You will not receive any payment or other compensation for taking part in this study. 
 
Will it cost me anything to participate in this study?  
 
Taking part in this study will not involve added costs to you. All study drugs (a single dose 
divided into three tablets) will be given free of charge by the research study. You and/or your 
insurance company will have to pay for any costs that are part of your regular medical care.  
 
What will happen if I am injured because I took part in this study? 
 
If you are injured as a result of this research, only immediate, essential, short-term medical 
treatment as determined by the participating hospital, will be available for the injury without 
charge to you personally.  
 
 
No monetary compensation will be offered.  
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 
You are not waiving any of your legal rights by signing this informed consent document.  
 
If additional treatment is required as a result of a physical injury related to the research, 
necessary medical treatment will be provided to you and billed to your insurance 
company or to you as part of your medical expenses.  
 
Immediately report any discomforts, problems or injuries you experience during the course of 
your participation in the study to Dr. Andrew Chang at 718-920-6626.  
 
What else do I have to do? 
 
 
You must tell the research personnel about any past and present diseases or allergies 
you are aware of and about all medications you are taking including “over-the-counter” 
remedies and nutritional supplements or herbs. 
 
You must take your study drug as instructed. 
 
If you do not feel well at any time, call your doctor or the research study doctor 
immediately.  
 
Drugs may cause a reaction that, if not treated promptly, could be life-threatening.  
It is important that you report all symptoms, reactions and other complaints to the 
research personnel.  
 
 
Are there any risks to me?  
 
 
All pain medications have side effects, which include but are not limited to the following: 
o Common, not serious: blurred vision; constipation; difficulty breathing; dizziness; 
drowsiness; flushing; lightheadedness; mental/mood changes; nausea; vomiting. 
o Rare, but serious: Severe allergic reactions (rash; hives; itching; difficulty 
breathing; chest tightness; swelling of the mouth, face, lips, or tongue); anxiety; 
change in the amount of urine; change or loss in hearing; fear; interrupted 
breathing; mental or mood changes; unusual tiredness, gastrointestinal bleeding, 
kidney impairment, hypotension (low blood pressure), bradycardia (low heart 
rate), respiratory depression (slowed breathing), and oxygen desaturation 
(decreased oxygen carried by your blood). 
 
There may be other risks of the four study drugs that are currently unknown. 
 
Confidentiality 
We will keep your information confidential, however, a risk of taking part in this study is that your 
confidential information might be shared accidentally with someone who is not on the study 
team and is not supposed to see or know about your information. This is very unlikely, because 
the study team takes confidentiality of your information seriously. Your research records will be 
kept confidential and your name will not be used in any written or verbal reports. Your 
information will be given a code number and separated from your name or any other information 
that could identify you. The form that links your name to the code number will be kept in a 
locked file cabinet and only the investigator and study staff will have access to the file. All 
information will be kept in a secure manner and computer records will be password protected. 
Your study information will be kept by the principal investigator, Dr. Andrew Chang, as long as it 
is useful for his research on pain. 
 
The only people who can see your research records are: 
 the research team and staff who work with them 
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 clinicians and staff at Montefiore who review your records for your care 
 groups that review research (the Einstein IRB, the Office for Human Research 
Protections, and the US Food and Drug Administration) 
 
These people who receive your health information, may not be required by privacy laws to 
protect it and may share your information with others without your permission, if permitted by 
laws governing them.  All of these groups have been asked to keep your information 
confidential. 
 
Risks to Women Who Are or May Become Pregnant 
The effect of the study drugs on an embryo or fetus (developing baby still in the womb), or on a 
breastfeeding infant, is unknown and may be harmful.  Because of these unknown risks, women 
cannot take part in this study if they are: 
 
Pregnant 
 
Trying to become pregnant 
 
Breastfeeding or sharing breast milk 
 
If you are a menopausal woman and have not had a menstrual period for the past 12 months or 
more, you will not need to have a pregnancy test.  Also, you will not need to have a pregnancy 
test if you have had a hysterectomy (surgical removal of your uterus and/or ovaries).  All other 
female subjects must have a negative pregnancy test (either by blood or urine) before starting 
the study drug.  In the case of a blood test, approximately 1 tablespoon would be drawn. 
 
Allergic Reaction to Study Drug 
Any drug can cause an allergic reaction which could be mild or more serious and can even 
result in death.  Common symptoms of an allergic reaction are rash, itching, skin problems, 
swelling of the face and throat, or trouble breathing. However, when most opioids (hydrocodone, 
oxycodone, codeine) cause hives (an itchy rash) they do so through a non-allergic mechanism. 
If you are having trouble breathing, tell a nurse or the study doctor immediately, or if you have 
already left the ED, call 911 immediately. 
 
 
New Findings 
If we learn any significant new findings during the study that might influence your decision to 
participate, we will contact you and explain them. 
 
Unknown Risks 
We have described all the risks we know. However, because this is research, there a possibility 
that you will have a reaction that we do not know about yet and is not expected.  
  
Are there possible benefits to me?  
 
You may or may not receive personal, direct benefit from taking part in this study. The possible 
benefits of taking part in this study include being assigned to a group whose medication results 
in better pain relief.  In addition, the information learned from this study may, in the future, 
benefit other patients who receive pain medication while in the ER.   
 
 
IRB NUMBER: 2014-4156
IRB APPROVAL DATE: 05/27/2015
IRB EXPIRATION DATE: 03/26/2016


Einstein IRB Greater Than Minimal Risk Template v. 12/12/2014 
Page 5 of 5 
What choices do I have other than participating in this study? 
 
You can refuse to participate in the study. If you decide not to participate, the medical care 
providers at this facility will still give you all of the standard care and treatment that is 
appropriate for you.  It is very likely that you will receive one of the same pain pills even if you 
don’t participate in this study.  
   
 
 
Are there any consequences to me if I decide to stop participating in this study? 
 
No. If you decide to take part, you are free to stop participating at any time without giving a 
reason. This will not affect your care and you will continue to be treated at this facility. However, 
some of the information may have already been entered into the study and that will not be 
removed.  
 
 
 
CONSENT TO PARTICIPATE 
I have read the consent form and I understand that it is up to me whether or not I participate. I 
know enough about the purpose, methods, risks and benefits of the research study to decide 
that I want to take part in it. I understand that I am not waiving any of my legal rights by signing 
this informed consent document. I will be given a signed copy of this consent form. 
 
Printed name of participant 
Signature of participant 
Date 
Time 
Printed name of the person 
conducting the consent 
process 
Signature 
Date 
Time 
 
IRB NUMBER: 2014-4156
IRB APPROVAL DATE: 05/27/2015
IRB EXPIRATION DATE: 03/26/2016