Adverse Event, Analgesia, Musculoskeletal Pain
Conditions
Keywords
emergency department, ketorolac, musculoskeletal pain, non-inferiority, adverse event
Brief summary
The purpose of this study was to evaluate a single 15 mg intramuscular (IM) dose of ketorolac for analgesic non-inferiority versus a single 60 mg IM dose for the treatment of acute MSK pain in a military emergency department (ED) that services Department of Defense (DoD), Department of Veteran Affairs (VA), and foreign military beneficiaries
Detailed description
The primary purpose of this study is to evaluate a single 15 mg IM dose of ketorolac for analgesic non-inferiority versus a single 60 mg IM dose for the treatment of acute MSK pain in a military ED that services Department of Defense (DoD), Department of Veteran Affairs (VA), and foreign military beneficiaries. The authors chose to evaluate 15 mg rather than the previously identified 10 mg dose for ease of administration as ketorolac is manufactured in 15 mg/mL, 30 mg/mL, and 60 mg/2mL vials in the U.S. The dose of ketorolac served as the primary independent variable for the study and the change in Visual Analog Scale (VAS) score served as the dependent variable. Prescribing the minimally effective doses of NSAIDs is pertinent to prevent and reduce the number of adverse events. Thus, the secondary outcome assessed for the dose-dependence of subjective and objective adverse events with ketorolac.
Interventions
DRUGKetorolac Injection 15 mg
A single dose of 15 mg ketorolac administered intramuscularly.
DRUGKetorolac Injection 60 mg
A single dose of 60 mg ketorolac administered intramuscularly.
Sponsors
William Beaumont Army Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
The patient was unaware of the dosage of ketorolac they received.
Intervention model description
Single blinded, randomized, non-inferiority
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Tricare beneficiaries between 18-55 years of age * Triaged as Emergency Severity Index 4 or 5 * Presenting to the William Beaumont Army Medical Center Emergency Department with a chief complaint of acute MSK pain (i.e., general muscular, neck, back, shoulder, arm, forearm, elbow, wrist, finger, hip, knee, thigh, leg, ankle, foot, or digits) * Pain intensity of 20 mm or greater on a standard 100 mm visual analog scale * Who the attending provider concurred with ketorolac IM administration for analgesia.
Exclusion criteria
* Body weight less than 50 kg (110 lbs.) * Younger than 18 or older than 55 years * Pregnant or breast feeding * History of: confirmed, unconfirmed, known, unknown, or suspected peptic ulcer disease, intestinal hemorrhage, renal insufficiency, hepatic insufficiency, cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, dark stools, bright red blood per rectum, hemoptysis, easy bruising, or high risk of bleeding * Unable to confidently convey or unknown medical history * Allergy or hypersensitivity to nonsteroidal anti-inflammatory drugs or aspirin * Systolic blood pressure \<90 or \>180 mmHg * Pulse rate \<50 or \>150 beats/min * Any over-the-counter or prescribed opioid and/or non-opioid analgesic medication (oral, per rectum, topical or parenteral) taken within 12 hours of ED presentation * Advised by any medical provider to not receive NSAIDs for any reason * Pain duration greater than 30 days (including acute on chronic pain) * Refusal to remain in the WBAMC ED for up to 60 minutes after injection of ketorolac * Patients currently taking anticoagulant medications * Concurrent use of medications which are contraindicated with concomitant NSAID use (drugs include aspirin, probenecid and pentoxifylline).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference of Visual Analog Scale Scores | 60 minutes from administration of medication | The mean difference of Visual Analog Scale scores between the two treatment groups measured at 60-minutes. The Visual Analog Scale used measures from 0 mm to 100mm. A higher score represents more degree of change. 13 mm was used as the non-inferiority margin. A difference between the two groups less than 13 mm demonstrates that 15 mg is non-inferior to 60 mg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference of Visual Analog Scale Scores | 30 minutes from administration of medication | The mean difference of Visual Analog Scale scores between the two treatment groups measured at 30-minutes. The Visual Analog Scale used measures from 0 mm to 100mm. A higher score represents more degree of change. 13 mm was used as the non-inferiority margin. A difference between the two groups less than 13 mm demonstrates that 15 mg is non-inferior to 60 mg. |
| Number of Participants With Adverse Events Related to the Administration of Ketorolac | At time of administration, 30 minutes after administration, and 60 minutes after administration. | The incidence of observed objective and reported subjective adverse events related to the administration of ketorolac. |
Countries
United States
Participant flow
Pre-assignment details
For the duration of our study, no study subjects were excluded or disenrolled.
Participants by arm
| Arm | Count |
|---|---|
| 15 mg Ketorolac Intramuscular Patients who received a single 15 mg dose of ketorolac administered intramuscularly
Ketorolac Injection 15 mg: A single dose of 15 mg ketorolac administered intramuscularly. | 55 |
| 60 mg Ketorolac Intramuscular Patients who received a single 60 mg dose of ketorolac administered intramuscularly
Ketorolac Injection 60 mg: A single dose of 60 mg ketorolac administered intramuscularly. | 55 |
| Total | 110 |
Baseline characteristics
| Characteristic | 15 mg Ketorolac Intramuscular | 60 mg Ketorolac Intramuscular | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 14 Participants | 31 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 41 Participants | 79 Participants |
| Age, Continuous | 31.1 years | 30.7 years | 30.9 years |
| Duration of pain | 69.8 minutes | 66.3 minutes | 68 minutes |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 55 participants | 55 participants | 110 participants |
| Sex: Female, Male Female | 13 Participants | 17 Participants | 30 Participants |
| Sex: Female, Male Male | 42 Participants | 38 Participants | 80 Participants |
| Weight in kilograms | 82.8 kg | 84.5 kg | 83.7 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 55 |
| other Total, other adverse events | 1 / 55 | 9 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 |
Outcome results
Primary
Mean Difference of Visual Analog Scale Scores
The mean difference of Visual Analog Scale scores between the two treatment groups measured at 60-minutes. The Visual Analog Scale used measures from 0 mm to 100mm. A higher score represents more degree of change. 13 mm was used as the non-inferiority margin. A difference between the two groups less than 13 mm demonstrates that 15 mg is non-inferior to 60 mg.
Time frame: 60 minutes from administration of medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 mg Ketorolac Intramuscular | Mean Difference of Visual Analog Scale Scores | -29.74 score on a scale | Standard Deviation 22.46 |
| 60 mg Ketorolac Intramuscular | Mean Difference of Visual Analog Scale Scores | -29.85 score on a scale | Standard Deviation 23.14 |
Secondary
Mean Difference of Visual Analog Scale Scores
The mean difference of Visual Analog Scale scores between the two treatment groups measured at 30-minutes. The Visual Analog Scale used measures from 0 mm to 100mm. A higher score represents more degree of change. 13 mm was used as the non-inferiority margin. A difference between the two groups less than 13 mm demonstrates that 15 mg is non-inferior to 60 mg.
Time frame: 30 minutes from administration of medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 mg Ketorolac Intramuscular | Mean Difference of Visual Analog Scale Scores | -18.99 score on a scale | Standard Deviation 17.73 |
| 60 mg Ketorolac Intramuscular | Mean Difference of Visual Analog Scale Scores | -17.31 score on a scale | Standard Deviation 18.31 |
Secondary
Number of Participants With Adverse Events Related to the Administration of Ketorolac
The incidence of observed objective and reported subjective adverse events related to the administration of ketorolac.
Time frame: At time of administration, 30 minutes after administration, and 60 minutes after administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 15 mg Ketorolac Intramuscular | Number of Participants With Adverse Events Related to the Administration of Ketorolac | 1 Participants |
| 60 mg Ketorolac Intramuscular | Number of Participants With Adverse Events Related to the Administration of Ketorolac | 9 Participants |