Comparison of Ketorolac at Three Doses in Children With Acute Pain

NCT05641363 | Completed Phase 3

• 1 other identifier: KETODOSE20221107
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 2

Brief Summary

Hospital Scene #1: A 6-year-old arrives in the Emergency Department at McMaster Children's Hospital (MCH) complaining of pain in his lower right side. His Dad explains the pain has been going on for a few hours and that Advil and Tyelnol haven't helped at all. He's anxious and concerned about his son because he never complains about pain - so this must be bad. After he has been seen by the doctor, the appendix appears to be the problem and the boy needs to have it removed. Dad wants his son's pain to go away but is worried because he once got a high dose of a medication and had some unwanted side effects. Hospital Scene #2: A 14-year-old girl has been experiencing migraine headaches for the past months and is awaiting an appointment with a specialist. Today, however, the pain is the worst it's been. Mom has picked her up from school and brought her to MCH not knowing what else to do to help her. The Advil and Tylenol have not improved her pain. She desperately wants the pain to go away but is worried because she read that some pain medicines are used without any studies done to see if they work and if they are safe. (https://www.ottawalife.com/article/most-medications-prescribed-to-children-have-not-been-adequately-studied?c=9). In both cases, these children need medicine to help their pain. The treating doctors want to give them pain medicine that will 1) be safe and 2) make the pain go away. This is what parents and the child/teenager, and the doctors want too. Some pain medicines like opioids are often used to help with pain in children. Unfortunately, opioids can have bad side effects and can, when used incorrectly or for a long time, be addictive and even dangerous. A better option would be a non-opioid, like Ketorolac, which also helps pain but is safer and has fewer side effects. The information doctors have about how much Ketorolac to give a child, though, is what has been learned from research in adults. Like with any medication, the smallest amount that a child can take while still getting pain relief is best and safest. Why give more medicine and have a higher risk of getting a side effect, if a lower dose will do the trick? This is what the researchers don't know about Ketorolac and what this study aims to find out. Children 6-17 years old who are reporting bad pain when they are in the Emergency Department or admitted in hospital and who will be getting an intravenous line in their arm will be included in the study. Those who want to participate will understand that the goal of the study is to find out if a smaller amount of medicine improves pain as much as a larger amount. By random chance, like flipping a coin, the child will be placed into a treatment group. The difference between these treatment groups is the amount of Ketorolac they will get. One treatment will be the normal dose that doctors use at MCH, and the other two doses will be smaller. Neither the patient, parent nor doctor will know how much Ketorolac they are getting. Over two hours, the research nurse or assistant will ask the child how much pain they are in. Our research team will also measure how much time it took for the pain to get better, and whether the child had to take any other medicine to help with pain. The research team will also ask families and patients some questions to understand their perceptions of pain control, pain medicines and side effects they know of. This research is important because it may change the way that doctors treat children with pain, not just at MCH but around the world. The results of this study will be shared with doctors through conferences and scientific papers. It's also important that clinicians share information with parents and children so that they can understand more about pain medicines and how these medicines can be used safely with the lowest chance of side effects.

Conditions

Acute Pain; Abdominal Pain; Migraine; Appendicitis Acute; Renal Colic; Biliary Colic

Outcome Measures

Primary Outcomes (1)

• Pain relief

  Between each low-dose ketorolac group (B1 and B2) and standard group (A) mean differences in pain as measured on an 11-point verbal Numerical Rating Scale (0 is no pain and 10 is worst pain ever)

  60 minutes post drug administration

Secondary Outcomes (6)

• Pain relief

  8 hours post study drug administration

• Pain relief by a minimally important difference (MID)

  60 and 120 minutes post study drug administration

• Change in category of pain

  30, 90, 120 minutes and 6 hours post study drug administration

• Time to effective analgesia

  Within 8 hours post study drug administration

• Rescue analgesia use

  Within 8 hours post study drug administration

Other Outcomes (3)

• Safety outcome 1

  Within 8 hours post study drug administration

• Safety outcome 2

  Within 8 hours post study drug administration

• Survey to understand patients' and caregivers' knowledge, attitudes, perceptions, and emotions on pain, medications, and their use in treating acute pain.

  Within 7-days of pain outcome completion.

Study Arms (3)

Standard dose group A

ACTIVE COMPARATOR

IV ketorolac 0.5 mg/kg/dose up to a maximum dose of 30 mg plus IV normal saline placebo given at 0.25 mg/kg to a maximum of 30 mg plus IV normal saline placebo given at 0.5 mg/kg to a maximum of 10 mg

Drug: Ketorolac Tromethamine

Low dose group B1

EXPERIMENTAL

IV ketorolac 0.5 mg/kg to a maximum of 10 mg plus IV normal saline placebo given at 0.25 mg/kg to a maximum of 30 mg plus IV normal saline placebo given at 0.5 mg/kg to a maximum of 30 mg

Drug: Ketorolac Tromethamine

Low dose group B2

EXPERIMENTAL

IV ketorolac 0.25 mg/kg to a maximum of 30 mg plus IV normal saline placebo given at 0.5 mg/kg to a maximum of 30 mg plus IV normal saline placebo 0.5 mg/kg to a maximum of 10 mg

Drug: Ketorolac Tromethamine

Interventions

Ketorolac Tromethamine DRUG

ketorolac tromethamine, an NSAID belonging to a group of non-opioid analgesics that inhibit the synthesis of prostaglandins and thromboxanes with strong analgesic and anti-inflammatory properties. It is the only non-opioid parenteral non-sedating analgesic available for use to treat acute pain in the emergency department.

Also known as: ketorolac, toradol, intravenous ketorolac

Low dose group B1; Low dose group B2; Standard dose group A

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6.0 years to \<18 years: primary outcome measure, 11-point vNRS is validated for use in children ≥6 years, and no other evidence-based acute pain measure is recommended for use in younger children Currently experiencing moderate to severe pain (self-reported pain score \>4 using the vNRS at the time of enrollment; ketorolac is used to treat moderate to severe pain)
• Patients seen in the ED or inpatient setting with acute pain ≤30 days in duration
• Patient with IV cannula in situ or ordered (to minimize any additional pain or distress)

You may not qualify if:

• Previous enrollment in trial (to ensure all observations are independent and not paired)
• Post-operative patient (as this included medically induced pain, versus pathology-only)
• Ketorolac 6 hours and/or opioids 4 hours prior to recruitment (avoid over-dosing and confounding)
• Use of daily analgesic for any indications (confounding as response to analgesics maybe altered)
• Caregiver and/or child cognitive impairment (precludes the ability to respond to study questions)
• History of gastrointestinal bleed or ulcers, inflammatory bowel disease, coagulation disorders, cerebrovascular bleeding, known arterio-vascular malformations (increased bleeding risk)
• History of chronic and active renal disease, excluding renal calculi and urinary tract infections
• History of chronic and active hepatocellular disease (ketorolac is metabolized in the liver)
• Known pregnancy at the time of enrollment (risk of closure of patent ductus arteriosus in fetus)
• Known hypersensitivity to NSAIDs or opioids
• Inability to obtain consent (language barrier and the absence of language translator)

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• McMaster University: collaborator

Study Sites (2)

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L9H6k6, Canada

Location

Related Publications (1)

• Eltorki M, Carciumaru R, Ali S, Holbrook A, Livingston M, Samiee-Zafarghandy S, Beattie K, Thabane L, Giglia L. Comparison of Ketorolac at 3 Doses in Children With Acute Pain: Protocol for A Randomized Controlled Trial. JMIR Res Protoc. 2025 Sep 26;14:e76554. doi: 10.2196/76554.

  PMID: 41066173 DERIVED

MeSH Terms

Conditions

Acute Pain; Abdominal Pain; Migraine Disorders; Appendicitis; Renal Colic

Interventions

Ketorolac Tromethamine; Ketorolac

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intraabdominal Infections; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double dummy design
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: December 7, 2022
• Study Start: June 1, 2023
• Primary Completion: April 24, 2025
• Study Completion: May 6, 2025
• Last Updated: July 9, 2025

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 20 years

Locations

CA (2)