Intravenous Ketorolac Vs. Morphine In Children With Acute Abdominal Pain

NCT06160778 | Recruiting Phase 3 DMC

• 1 other identifier: 23-0952
• Study Type: interventional
• Target: 495
• Locations: 1 country
• Sites: 1

Brief Summary

Appendicitis is a common condition in children 6-17 years of age, and the top reason for emergency surgery in Canada. Children with appendicitis can have very bad pain in their belly. Children often need pain medications given to them through a needle in their arm called an intravenous (IV). The most common IV pain medication is a type of opioid called morphine. We know that opioids work well to improve pain, but there are risks and side effects when taking them. There are non-opioid medications that doctors can give to patients, like ketorolac. Ketorolac helps decrease inflammation and pain and has fewer side effects when a patient takes it for a short period of time. Our past and present overuse of opioids, driven by an unproven assumption that opioids work best for pain, resulted in an Opioid Crisis and doctors are now looking for alternatives. To do this, we need to prove that there are other options to treat children's pain that are just as good as opioids, with less side effects. The goal of our study is to discover if school aged children who arrive at the emergency department with belly pain, improve just as much with ketorolac as they do with morphine. To answer this question, we will need a very large number of patients in a study that includes several hospitals across Canada. With a flip of a coin, each participant will either get a single dose of morphine or a single dose of ketorolac. To make sure that our pain assessment is impartial, no one will know which medicine the child received except the pharmacist who prepared the medicine.

Conditions

Acute Pain; Abdomen, Acute; Abdominal Pain; Appendicitis; Emergencies; Child, Only

Outcome Measures

Primary Outcomes (1)

• Pain relief as measured on the verbal numerical rating scale

  Between group 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 (21)

• Pain relief as measured on the verbal numerical rating scale

  30 minutes post drug administration

• Pain relief as measured on the verbal numerical rating scale

  90 minutes post drug administration

• Pain relief as measured on the verbal numerical rating scale

  120 minutes post drug administration

• Pain relief as measured on the verbal numerical rating scale

  6 hours post drug administration

• Pain relief as measured on the verbal numerical rating scale during the ultrasound diagnostic

  up to 6 hours post drug administration

Other Outcomes (1)

• Appendix visualization on ultrasound

  post-randomization and up to 8 hours post-intervention.

Study Arms (2)

Ketorolac Tromethamine

EXPERIMENTAL

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 in Canada for use to treat acute pain in the emergency department.

Drug: Ketorolac Tromethamine; Drug: normal saline

Morphine Sulfate

ACTIVE COMPARATOR

An intravenous opioid that is commonly used as part of usual care for treament of pain in patients with acute abdominal pain and suspected appendicitis.

Drug: Morphine Sulfate; Drug: Normal saline

Interventions

Ketorolac Tromethamine DRUG

Intravenous ketorolac given at 0.5 mg/kg of body weight up to a maximum of 30 mg in a single dose.

Ketorolac Tromethamine

Morphine Sulfate DRUG

Intravenous morphine given at 0.1 mg/kg of body weight up to a maximum of 5 mg in a single dose.

Morphine Sulfate

Normal saline DRUG

Intravenous normal saline placebo (labelled as morphine) given at 0.1 mg/kg of body weight up to a maximum of 5 mg in a single dose.

Also known as: Morphine Sulfate Placebo

Ketorolac Tromethamine

Eligibility Criteria

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

You may qualify if:

• Age 6 to 17 years
• Abdominal pain ≤5 days duration
• Acute abdominal pain that is being investigated (suspected) by the clinical team for appendicitis
• Patient with IV cannula in situ or ordered
• Currently experiencing moderate to severe abdominal pain at rest or with movement: self-reported pain score ≥5 using the verbal Numerical Rating Scale

You may not qualify if:

• Previous enrollment in the trial
• NSAID use within 3 hours and/or opioid use within 1 to 2 hours (1 hour post-IV or intra-nasal fentanyl and 2 hours post IV morphine).
• Children who need immediate resuscitation, are hemodynamically unstable as deemed by the clinical team or have a Canadian Triage Assessment Score of 1
• Significant caregiver and/or child cognitive impairment precluding the ability to complete study questions.
• Chronic pain requiring daily analgesic use: confounding as response to analgesics maybe altered.
• History of severe undiagnosed gastrointestinal bleeding requiring medical intervention, peptic or duodenal ulcer disease or inflammatory bowel disease, coagulation disorders, prior cerebrovascular bleeding, known arterio-vascular malformations. History of minor gastrointestinal bleeding from conditions such as resolved fissures, polyps or allergic colitis will not exclude patients from participating.
• History of chronic and active interstitial kidney disease
• History of chronic and active hepatocellular disease: ketorolac is metabolized by the liver.
• Known or suspected pregnancy at the time of enrollment or breastfeeding females
• Known hypersensitivity to NSAIDs or opioids.
• Absence of a parent/guardian for children who are \<16 years of age if they are not a mature minor.
• Inability to obtain consent due to a language barrier and the absence of language translator in person or by a phone translation service available in the ED.

Sponsors & Collaborators

• University of Calgary: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Alberta Children's Hospital Emergency Department

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

MeSH Terms

Conditions

Acute Pain; Abdomen, Acute; Abdominal Pain; Appendicitis; Emergencies

Interventions

Ketorolac Tromethamine; Morphine; Saline Solution

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Intraabdominal Infections; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Mohamed Eltorki, MBChB

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamed M Eltorki, MBChB, MSc

CONTACT

+1403-955-7723; mmeltork@ucalgary.ca

Angela Wallace

CONTACT

403-955-5451; angela.wallace@ahs.ca

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: SPONSOR

Model Details: Two parallel interventional groups.

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 7, 2023
• Study Start: May 27, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 24, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: within 10 years of study completion

Locations

CA (1)