Intramuscular Ketorolac at Two Single-Dose Regimens

Comparison of Intramuscular Ketorolac at Two Single-Dose Regimens for Treatment of Acute Musculoskeletal Pain in a Military Emergency Department: A Randomized Controlled Non-Inferiority Trial

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

Study Overview

• Status: Completed
• Conditions: Musculoskeletal Pain; Analgesia; Adverse Event
• Intervention / Treatment: Drug: Ketorolac Injection 15 mg; Drug: Ketorolac Injection 60 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • El Paso, Texas, United States, 79920
      • William Beaumont Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 15 mg ketorolac intramuscular; Patients who received a single 15 mg dose of ketorolac administered intramuscularly	Drug: Ketorolac Injection 15 mg; A single dose of 15 mg ketorolac administered intramuscularly.; Other Names: ketorolac; toradol; ketorolac tromethamine
ACTIVE_COMPARATOR: 60 mg ketorolac intramuscular; Patients who received a single 60 mg dose of ketorolac administered intramuscularly	Drug: Ketorolac Injection 60 mg; A single dose of 60 mg ketorolac administered intramuscularly.; Other Names: ketorolac; Toradol; ketorolac tromethamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference of Visual Analog Scale scores between the two groups	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.	60 minutes from administration of medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference of Visual Analog Scale scores between the two groups	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.	30 minutes from administration of medication
Incidence of adverse events related to the administration of ketorolac	The incidence of observed objective and reported subjective adverse events related to the administration of ketorolac.	At time of administration, 30 minutes after administration, and 60 minutes after administration.

Collaborators and Investigators

• Sponsor: William Beaumont Army Medical Center
• Investigators: Principal Investigator: Nathaniel J Turner, MPAS, Department of Emergency Medicine, William Beaumont Army Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 27, 2020
• Primary Completion (ACTUAL): November 9, 2020
• Study Completion (ACTUAL): November 9, 2020

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (ACTUAL): February 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 18, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: emergency department; ketorolac; non-inferiority; musculoskeletal pain; adverse event
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: C.2019.088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes