Dosing of Ketorolac for Four Classes of Complaints in the Emergency Department
Phase: PHASE4
Conditions: Acute Pain
Sponsor: University of Missouri-Columbia

Study Title: Dosing of ketorolac 
NCT: NCT03464461 
Date: 5/12/2021 
 
 
 

Dosing of ketorolac 
 
Kara Goddard Pharm.D., Julie Stilley PhD., Matthew Robinson MD 
 
 
 
 
 
 
05/12/2021 v6 
 
1. 
Objective and Specific Aims 
The non-steroidal anti-inflammatory drugs (NSAID’s) are very commonly used to treat pain in 
Emergency Departments.  In January of 2018 more than 1100 doses of the injectable NSAID 
ketorolac were given in the University of Missouri Emergency Department.  The correct dosing 
of ketorolac is unclear.   
Our study is designed to clarify the optimal dose of ketorolac. 
2.  
Background and Significance 
Background 
Optimal pain management in the Emergency Department remains problematic[1]. 
NSAID are a particularly useful class of drugs in Emergency Departments because of 
their effectiveness and safety[2].  The parenteral form of ketorolac has become 
particularly popular for treatment of acute pain in Emergency Departments, 
demonstrated by the total of more than 1100 doses given in the University of 
Missouri Emergency Department in January of 2018 (internal audit).  
 
Recently the optimal dosing of ketorolac has been questioned[3]. This study showed 
equal efficacy among three doses of intravenous ketorolac: the standard 30mg dose, 
15mg, and 10mg. These investigators recommended a change in practice to adopt the 
10mg dose as standard. 
 
Significance 
The correct dosing of analgesics and ketorolac is actually a complicated and poorly 
understood issue.  Ketorolac, as with other NSAID’s, has multiple properties that may 
influence its analgesic properties; it has anti-inflammatory properties similar to other 
NSAID, is an analgesic, and is an inhibitor of prostaglandin synthesis[2]. Also it has 
significant placebo effect in some circumstances. In a study of acute headaches in an 
Emergency Department three intramuscular injections were compared: meperidine 
50mg with 25mg promethazine, ketorolac 60mg, and saline[4].  The three treatments 
were found to be effective and equivalent.  The authors conclude that the placebo 
effect was so profound that analgesic effects could not be evaluated.  There is also 
evidence that ketorolac and other NSAID’s have different efficacy as a function of 

the type of pain[2]; that is, that pain which is inflammation medicated may be more 
very responsive.  
3.  
Objectives and Purpose 
This study is designed to determine the optimal dose of ketorolac in four groups of patients that 
would be expected to have different mechanisms of response to NSAID’s.  
 
4.  
Research Design and Methods 
 
Methods 
Patients presenting to the Emergency Department with  pain will be screened for 
inclusion into one of four groups: 
1. Headache: Non-traumatic headache of less than four days duration. 
2. Trauma: Patients with acute mild to moderate musculo-skeletal injury (no trauma 
activation) or pain of less than four days duration. 
3. Colic/Abdominal pain: Patients with mild to moderate abdominal or flank pain of 
less than four days duration. 
4. Viral syndrome: Patients with less than four days of generalized systemic 
complaints suggestive of an acute viral syndrome. 
A pregnancy test will be administered to females of childbearing potential before 
administration of the study drug.  Patients will be randomized to receive either 30mg 
of ketorolac, 10mg of ketorolac, or saline as a slow intravenous infusion over 10 
minutes via a pump.  Thirty minutes or later their pain score will be re-evaluated, they 
will be assessed for any negative effects of the treatment, additional pain medications 
will be offered if indicated, and the patient’s involvement in the study will be 
concluded. 
Data collected: 
1. Patient demographics 
a. Age 
b. Sex 
c. Complaint 
2. Pain scores 
3. Side effects noted by patient or staff 
 
5.   
Subjects 
Subjects will be eligible for recruitment when they present to the Emergency Department with a 
chief complaint consistent with the four study groups.  Inclusion criteria will be: 

 
1. Age≥18y/o 
 
2. Not pregnant or lactating (negative urinary pregnancy test) 
 
3. No contraindication to ketorolac 
Exclusion criteria 
 
1. Age<18y/o 
 
2. Pregnancy or lactation 
 
3. Contraindication to ketorolac 
If the subjects are eligible for inclusion they will be offered inclusion in the study by one of the 
Emergency Department faculty.  If they refuse participation they will be treated in a standard 
fashion. 
 
6. 
Treatment of subjects 
There will be no long term follow up of patients for data. Subjects who have incomplete data will 
have their data discarded and removed from enrollment. 
 
7. 
Statistics 
End point: the primary hypothesis is that ketorolac has different effects depending on the dose 
and the condition. We will compare pain scores at 30 minutes or after for each of the doses and 
the groups. 
Sample size: We plan to enroll 170 patients in each group.  This is based on a change in pain 
scale of 2.5 with a standard deviation of 2.5, and αof 0.05 and power of 0.80[5].  
An interim analysis will be performed when half of the patients are enrolled in each group.  The 
study will be terminated if there is significant difference in the groups at this point.  Dr. Chelsea 
B. Deroche is providing statistical support for the project. 
8. 
Direct access to source data/documents 
Access to source data and documents will be provided by the investigators for any auditing or 
monitoring or reviews by the IRB/IEC, or regulatory inspections. 
 
9. 
Ethics 
This trial proposes to the study the proper dosing of ketorolac in several different conditions and 
attempts to clarify the placebo effect in this setting.  Standard care will not be withheld at any 
time during this protocol.  The intervention may offer significant benefit for the patients being 
studied.  An interim analysis is planned with termination of the study if this is the case. 
 

10. 
Data handling and recordkeeping 
 
Initial data collection will include identification of the patient by name and medical recorded 
number.  This data will be kept in a locked cabinet in the Emergency Medicine Department.  
Data will be extracted from these records and recorded in a computer data base and identified 
only by subject number.  No patient identifies will be entered in to the computer database. 
 
11. 
Investigators 
Starr-Mar’ee Bedy: Dr. Bedy in Pharm.D. with extensive training in the clinical use of the 
medications involved in this study and a history of working in the emergency department.  
 
Kara Goddard: Dr. Goddard in Pharm.D. with extensive training in the clinical use of the 
medications involved in this study whose clinical duties are in the Emergency Department. 
 
Matthew Robinson:  Dr. Robinson is an Associate Professor of Emergency Medicine. He is 
attending physician in the Emergency Department and routinely manages patients with headache. 
 
Julie Stilley: Dr. Stilley is Research Assistant Professor in the Department of Emergency 
medicine and has extensive training in research. 
 
 
 
12.  
Financing and insurance 
 
Patients will have regular charges for Emergency Department visit but will not be charged for 
ketorolac/placebo or its administration.  Charges for any treatment will be per usual.  There will 
be no payments to the subjects. 
 
13. 
References 
 
1. 
Patrick, P.A., et al., Timely pain management in the emergency department. Journal of 
Emergency Medicine, 2015. 48(3): p. 267-73. 
2. 
Catapano, M.S., The analgesic efficacy of ketorolac for acute pain. Journal of Emergency 
Medicine, 1996. 14(1): p. 67-75. 
3. 
Motov, S., et al., Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for 
Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Annals of 
Emergency Medicine, 2017. 70(2): p. 177-184. 
4. 
Harden, R.N., et al., The placebo effect in acute headache management: ketorolac, meperidine, 
and saline in the emergency department. Headache, 1996. 36(6): p. 352-6. 
5. 
Glantz, S.A., Primer of biostatistics. 7 ed. 2012: McGraw-Hill. 
 

 
 
________________________________________    ______________________ 
Signature                                                                              Date 
Matthew Robinson, MD, Emergency Medicine Department, University of Missouri-Columbia