A Phase 3 interventional study of Ketorolac Tromethamine and Morphine Sulfate in Acute Pain, Abdomen, Acute and Abdominal Pain, sponsored by University of Calgary. Recruiting at 1 site in Canada. Open to participants aged 6 Years to 17 Years. Per ClinicalTrials.gov, last updated 2024-06-24.
Sponsored by University of Calgary · Phase 3, Interventional, and Treatment
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.
Background: Appendicitis, the most common surgical diagnosis in Canadian children aged 6-17 years, accounts for \~8000 admissions annually. Despite an ongoing opioid crisis, prescription narcotics remain a mainstay analgesic for children with suspected appendicitis. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), which has a safer adverse event (AE) profile than opioids, is commonly used in emergency departments (EDs) for adults; however, use in children is considered off label due to a lack of randomized trials in this patient population. We propose a multi-centre clinical trial to address this knowledge gap,informed by our team's successful pilot trial.
Specific Aim 1: To determine if administering intravenous (IV) ketorolac is non inferior to IV morphine in reducing mean pain scores in children with suspected appendicitis.
Hypothesis: IV ketorolac will be non-inferior to IV morphine
Specific Aim 2: To determine between group differences in rates of AEs. Hypothesis: IV ketorolac will be associated with less AEs than IV morphine.
Design: A randomized quadruple blind (participant, clinician, outcome assessor, investigator) parallel group double-dummy trial in 4 Canadian pediatric EDs. Eligible patients will be 6-17 years with 5-days of moderate-severe pain (vNRS ≥5 ) being investigated for suspected appendicitis, with intravenous (IV) access, will be randomized to either:
Primary outcome: Between-group mean difference in pain on the vNRS at 60 minutes following administration.
Safety outcome: Proportion of children experiencing AEs related to study drug administration.
Secondary Outcomes: Between-group differences: (1) pain relief as measured on vNRS at 30, 90 and 120 minutes and at 6-8 hours; (2) proportion who achieves a 2-point vNRS (minimal important difference) pain score reduction at 60 and 120 minutes; (3) proportion of patients who change their baseline pain category (vNRS: mild 0-3, moderate 4-6, severe ≥7) at each time point; (4) time to effective analgesia as measured by the time when vNRS of \<3 is achieved (5) proportion of patients requiring additional analgesia; (6) total opioids administered (i.e., morphine equivalent mg/kg within 8 hours of treatment); (7) frequency of specific types of AEs (e.g., dizziness); (8) frequency of delayed appendicitis diagnosis; and (9) Ramsay Sedation Score at 30, 60, 90 and 120 minutes.
Sample size:With a non-inferiority margin of 1.0 (50% of the minimal important difference), 600 participants would give a power of 0.9 (1- β) to establish non-inferiority of ketorolac vs. morphine (significance level α = 0.05).
1,073 studies on the registry are indexed under Acute Pain; 166 are open to participants now.
This study's planned enrollment of 495 is above the median of 86 across 902 interventional studies indexed under Acute Pain.
Browse Acute Pain studies →University of Calgary is the lead sponsor of 703 studies on the registry; 196 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 2 (20%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Intravenous ketorolac given at 0.5 mg/kg of body weight up to a maximum of 30 mg in a single dose.
Intravenous morphine given at 0.1 mg/kg of body weight up to a maximum of 5 mg in a single dose.
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
Intravenous normal saline placebo (labelled as ketorolac) given at 0.5 mg/kg of body weight up to a maximum of 30 mg in a single dose.
Also known as: Ketorolac Tromethamine Placebo
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)
Time frame: 60 minutes post drug administration
Pain relief as measured on the verbal numerical rating scale
Between group mean differences in pain as measured on an 11-point verbal
Time frame: 30 minutes post drug administration
Pain relief as measured on the verbal numerical rating scale
Between group mean differences in pain as measured on an 11-point verbal
Time frame: 90 minutes post drug administration
Pain relief as measured on the verbal numerical rating scale
Between group mean differences in pain as measured on an 11-point verbal
Time frame: 120 minutes post drug administration
Pain relief as measured on the verbal numerical rating scale
Between group mean differences in pain as measured on an 11-point verbal
Time frame: 6 hours post drug administration
Pain relief as measured on the verbal numerical rating scale during the ultrasound diagnostic
score from 0-10 on verbal numerical rating scale
Time frame: up to 6 hours post drug administration
Proportion who achieve the minimal important difference for pain relief
Proportion of participants who achieves the 2-point verbal Numerical Rating Scale minimal important difference pain score reduction
Time frame: 60 minutes post drug administration
Proportion who achieve the minimal important difference for pain relief
Proportion of participants who achieves the 2-point verbal Numerical Rating Scale minimal important difference pain score reduction
Time frame: 120 minutes post drug administration
Change in baseline pain category
Proportion of participants who change the severity of their baseline pain category. Pain categories on the verbal numerical rating scale as follows: mild = 0 to 4, moderate = 5 to 7, severe \>7)
Time frame: 30 minutes post drug administration
Change in baseline pain category
Proportion of participants who change the severity of their baseline pain category. Pain categories on the verbal numerical rating scale as follows: mild = 0 to 4, moderate = 5 to 7, severe \>7)
Time frame: 60 minutes post drug administration
Change in baseline pain category
Proportion of participants who change the severity of their baseline pain category. Pain categories on the verbal numerical rating scale as follows: mild = 0 to 4, moderate = 5 to 7, severe \>7)
Time frame: 90 minutes post drug administration
Change in baseline pain category
Proportion of participants who change the severity of their baseline pain category. Pain categories on the verbal numerical rating scale as follows: mild = 0 to 4, moderate = 5 to 7, severe \>7)
Time frame: 120 minutes post drug administration
Change in baseline pain category
Proportion of participants who change the severity of their baseline pain category. Pain categories on the verbal numerical rating scale as follows: mild = 0 to 4, moderate = 5 to 7, severe \>7)
Time frame: 6 hours post drug administration
Time to effective analgesia
Duration of time from time of drug administration to time at which a verbal Numerical Rating Scale ≤3 is achieved.
Time frame: up to 6 hours post drug administration
Additional analgesia requirment
Proportion of participants requiring any additional analgesia in each trial arm
Time frame: up to 6 hours post drug administration
Total opioids administered
total morphine-equivalent mg/kg administered for all trial participants
Time frame: up to 8 hours post drug administration
Ramsay sedation score
Assessment of sedation levels post drug administration; score is 1-6 (1 is alert, 6 is not responsive)
Time frame: 30 minutes post drug administration
Ramsay sedation score
Assessment of sedation levels post drug administration; score is 1-6 (1 is alert, 6 is not responsive)
Time frame: 60 minutes post drug administration
Ramsay sedation score
Assessment of sedation levels post drug administration; score is 1-6 (1 is alert, 6 is not responsive)
Time frame: 90 minutes post drug administration
Ramsay sedation score
Assessment of sedation levels post drug administration; score is 1-6 (1 is alert, 6 is not responsive)
Time frame: 120 minutes post drug administration
Adverse events per participant
Frequency of specific adverse event occurrence per participant enrolled
Time frame: up to 6 hours post drug administration
Frequency of each specific adverse event
Frequency of each specific adverse event occurrence
Time frame: up to 6 hours post drug administration
Appendix visualization on ultrasound
proportion of participants who had the appendix visualized on ultrasound
Time frame: post-randomization and up to 8 hours post-intervention.
Plan to share: Yes — At the completion of the study and publication of main manuscript, anonymized participant data can be shared upon reasonable request.
Supporting information: Study protocol, Statistical analysis plan
Time frame: within 10 years of study completion
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Studies of the drug tested here: Ketorolac Tromethamine