Ketorolac vs. Morphine for Acute Abdominal Pain in Children

(KETOAPP Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Mohamed Eltorki, MBChB

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: University of Calgary

Must not be taking: NSAIDs, Opioids

Disqualifiers: Cognitive impairment, Chronic pain, Pregnancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that participants have not used NSAIDs within 3 hours and opioids within 1 to 2 hours before enrollment. If you are currently taking these medications, you may need to stop them for a short period before participating.

What data supports the effectiveness of the drug ketorolac compared to morphine for acute abdominal pain in children?

Research shows that ketorolac is effective for pain relief in various conditions, such as postoperative pain and cancer pain, with fewer side effects compared to morphine. In a study on postoperative pain, ketorolac was found to be as effective as higher doses of morphine, with fewer reports of drowsiness.

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Is ketorolac safe compared to morphine for treating pain in children?

Ketorolac has been shown to be a safe and effective pain reliever in various studies, with fewer side effects compared to morphine, which can cause drowsiness and nausea. In studies involving both adults and children, ketorolac was generally well-tolerated, with fewer patients stopping its use due to side effects compared to morphine.

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How does the drug ketorolac differ from morphine for treating acute abdominal pain in children?

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that provides pain relief without the risk of respiratory depression or drug abuse potential associated with morphine, an opioid. While ketorolac may take longer to provide pain relief, it has a longer duration of action compared to morphine.

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Eligibility Criteria

This trial is for children aged 6-17 with severe belly pain, suspected of appendicitis, and who have or will get an IV. They must be in moderate to severe pain at rest or when moving, scoring ≥5 on a pain scale.

Inclusion Criteria

My abdominal pain has lasted 5 days or less.

I am being checked for appendicitis due to acute abdominal pain.

I have an IV line in place or one has been ordered for me.

Exclusion Criteria

I or my caregiver/child cannot complete study questions due to cognitive issues.

I have taken NSAIDs within 3 hours or opioids within 1-2 hours.

Known or suspected pregnancy at the time of enrollment or breastfeeding females

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of either IV ketorolac or IV morphine, with pain assessments conducted at multiple time points post-administration

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and additional analgesia requirements

8 hours

1 visit (in-person)

Participant Groups

The study compares the effectiveness of Ketorolac (a non-opioid) versus Morphine (an opioid) for treating acute abdominal pain in children. Participants are randomly given one dose of either drug without knowing which one they received.

Group I: Ketorolac Tromethamine Experimental Treatment 2 Interventions

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.

Group II: Morphine Sulfate Active Control 2 Interventions

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.

Ketorolac is already approved in United States, European Union, United States, United States, Switzerland for the following indications:

🇺🇸 Approved in United States as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea
• Idiopathic pericarditis
• Ocular itching

🇪🇺 Approved in European Union as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea

🇺🇸 Approved in United States as Acular for:

• Ocular itching
• Inflammation after eye surgery

🇺🇸 Approved in United States as Sprix for:

• Moderate to severe pain

🇨🇭 Approved in Switzerland as Ketorolac for:

• Moderate to severe pain
• Postoperative pain

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Alberta Children's Hospital Emergency Department Calgary, Canada

Who Is Running the Clinical Trial?

University of Calgary Lead Sponsor

Canadian Institutes of Health Research (CIHR) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. [2022] Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative pain. The 155 patient participants received single intramuscular doses of either ketorolac, 10, 30, or 90 mg, or morphine, 6 or 12 mg, administered in a double-blind, randomized fashion. Pain scores (verbal and visual analog) were recorded at baseline and assessed at 30 minutes and then hourly to 6 hours. Pain relief was rated at the same times. Ketorolac, 90 and 30 mg, was rated significantly better than morphine, 6 mg, at each assessment interval after 1 hour. Ketorolac, 90 and 30 mg, was rated similarly to morphine, 12 mg, for the first 3 hours and better than morphine, 12 mg, 4 hours after injection. There were no serious side effects reported. The only side effect reported in more than 3% of patients was 8% somnolence with morphine. This study shows ketorolac to be a safe and effective analgesic for relief of postoperative pain.

2. England pubmed.ncbi.nlm.nih.gov

Intravenous ketorolac versus morphine in children presenting with suspected appendicitis: a pilot single-centre non-inferiority randomised controlled trial. [2022] Despite a lack of evidence demonstrating superiority to non-steroidal anti-inflammatory drugs, like ketorolac, that are associated with lower risk of harms, opioids remain the most prescribed analgesic for acute abdominal pain. In this pilot trial, we will assess the feasibility of a definitive trial comparing ketorolac with morphine in children with suspected appendicitis. We hypothesise that our study will be feasible based on a 40% consent rate.

3. United States pubmed.ncbi.nlm.nih.gov

The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient. [2013] The control of postoperative pain in the pediatric orthopaedic patient is a challenging endeavor. Several studies have shown the efficacy of ketorolac tromethamine in the pediatric general surgical population, but its efficacy in the pediatric orthopaedic population remains unproven. Twenty-seven consecutive patients (age 6 months to 18 years) who underwent long-bone osteotomies or foot procedures by a group of three pediatric orthopaedic surgeons were given a ketorolac protocol (1 mg/kg loading, 0.5 mg/kg every 6 h for 24 h). Breakthrough pain was managed with morphine until the patient was able to take oral pain medication, as was any pain after the 24-h period for ketorolac expired. Thirty-seven age- and case-matched patients were used as retrospective controls. The patients in the study who received ketorolac required significantly fewer doses of morphine than did the control group (2.29 +/- 3.98 vs. 10.02 +/- 3.39; p

4. England pubmed.ncbi.nlm.nih.gov

Sublingual ketorolac versus sublingual tramadol for moderate to severe post-traumatic bone pain in children: a double-blind, randomised, controlled trial. [2016] To assess the effectiveness of sublingual ketorolac versus sublingual tramadol in reducing the pain associated with fracture or dislocation of extremities in children.

5. Greece pubmed.ncbi.nlm.nih.gov

Comparative-study of intramuscular ketorolac tromethamine and morphine in patients experiencing cancer pain. [2019] Ketorolac tromethamine administered intramuscularly (i.m.) 10 mg 6-hourly was compared with morphine 10 mg i.m. 6-hourly in a randomised, double-blind, cross-over trial for its analgesic efficacy and safety in 51 patients with moderate to severe cancer pain. There was no overall significant difference between the analgesic effect of the two treatments. 57% of ketorolac- and 74% of morphine-treated patients changed their analgesic. Among these, significantly more patients stopped ketorolac than morphine due to pain (p=0.007) whilst more patients discontinued morphine than ketorolac because of adverse effects (p=0.001), predominantly emesis. Only one patient (2%) stopped ketorolac because of intolerance. Ketorolac shows promise as an effective and well tolerated analgesic for cancer pain and merits further study.

6. United States pubmed.ncbi.nlm.nih.gov

The use of ketorolac in the management of postoperative pain. [2022] Ketorolac tromethamine (Toradol) is a nonsteroidal antiinflammatory drug (NSAID) available in intramuscular (IM) and oral formulations for the management of acute pain. Intramuscular ketorolac is the only parenteral NSAID available for analgesic use in the US. The clinical profile is reviewed, and clinical studies most applicable to a postoperative patient are discussed in detail. The results of a clinical study performed at Emory University School of Medicine are presented. In this single-dose study, 176 patients received either 10 mg of oral ketorolac, 5 mg or 10 mg of IM morphine, or placebo after orthopedic surgery. The analgesic efficacy of ketorolac was comparable to both doses of morphine and significantly superior to placebo. Ketorolac, when administered intramuscularly or orally, is a safe and effective analgesic agent for the short-term management of acute postoperative pain and can be used as an alternative to opioid therapy.

7. United States pubmed.ncbi.nlm.nih.gov

Comparative effects of three doses of intravenous ketorolac or morphine on emesis and analgesia for restorative dental surgery in children. [2018] The optimal dose of intravenous ketorolac tromethamine (ketorolac), a non-steroidal anti-inflammatory drug has not been determined in children. There are only limited published data on the use of intravenous ketorolac for paediatric analgesia. This study compares the analgesic and emetic effect of three different doses of ketorolac with morphine in paediatric dental surgical out-patients.

8. United States pubmed.ncbi.nlm.nih.gov

Ketorolac: an injectable NSAID. [2013] Ketorolac tromethamine is the first injectable nonsteroidal anti-inflammatory drug approved for the management of acute pain. In analgesic potency and ability to relieve postoperative pain, it is comparable to morphine. The advantages of ketorolac over opiates are the absence of respiratory depression and lack of drug abuse potential. Ketorolac has a longer duration of action than morphine, but it has less effect on the central nervous system. Ketorolac should not be used for obstetric analgesia.

9. United States pubmed.ncbi.nlm.nih.gov

Comparison of intravenous ketorolac with morphine for postoperative pain in children. [2019] Ninety-two children from 3 to 12 years of age were given intravenous morphine or ketorolac by titration, or ketorolac by bolus injection for moderate or severe postsurgical pain in a double-blind randomized parallel-group study. Pain scores were assessed every 5 minutes until pain relief was complete, and then every 15 minutes for 8 hours or until pain returned. Twenty-nine of 30 patients receiving morphine and 25 of 30 patients in each group receiving ketorolac achieved pain relief. The subjects in the morphine group required statistically fewer doses for analgesia than the subjects in the ketorolac groups. The sums of pain intensity differences calculated from the start of the study numerically favored morphine, but the sum of pain intensity differences from pain relief until 50% withdrew were significantly better in the ketorolac groups. Median durations of analgesia from initial drug administration were 170, 190, and 225 minutes in the morphine, ketorolac titration, and ketorolac bolus groups, respectively. The most common side effect was injection site pain. Analgesia after intravenous ketorolac developed more slowly but was sustained better than morphine.