Ketorolac vs. Morphine for Acute Abdominal Pain in Children

(KETOAPP Trial)

Overseen By Mohamed M Eltorki, MBChB, MSc

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Calgary

Must not be taking: NSAIDs, Opioids

Disqualifiers: Cognitive impairment, Chronic pain, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

495 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether ketorolac, a non-opioid pain reliever, matches the effectiveness of morphine for children with acute abdominal pain, possibly due to appendicitis. The researchers aim to identify a safer pain relief option with fewer side effects than opioids like morphine. Participants will randomly receive either ketorolac or morphine to compare their effects on pain relief. Children aged 6-17 with moderate to severe abdominal pain and suspected appendicitis may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially safer pain management options for children.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ketorolac is generally a safe choice for managing sudden pain in children. Studies have found it effectively reduces pain without causing major side effects when used for a short time. Ketorolac belongs to a group of medications called NSAIDs, which help lower inflammation and pain.

In contrast, morphine, a commonly used pain reliever, works well but can have more side effects, such as nausea, drowsiness, and even the risk of addiction with long-term use.

In the trial under consideration, both ketorolac and morphine will be given as a single dose. This method aims to reduce any potential side effects. By comparing these two treatments, researchers aim to determine if ketorolac can manage pain as effectively as morphine but with fewer risks. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for appendicitis?

Unlike the standard care for acute abdominal pain in children, which often relies on opioids like morphine, ketorolac offers a non-opioid alternative. Ketorolac is an NSAID that works by inhibiting the synthesis of prostaglandins and thromboxanes, providing strong pain relief without the sedative effects associated with opioids. Researchers are excited about ketorolac because it could reduce the risk of opioid-related side effects and dependency while effectively managing pain, making it a potentially safer option for kids.

What evidence suggests that this trial's treatments could be effective for acute abdominal pain in children?

This trial will compare Ketorolac and Morphine for treating acute abdominal pain in children. Research has shown that Ketorolac effectively manages sudden pain in emergency situations by reducing swelling and pain without causing drowsiness, unlike some other pain medications. While studies indicate that Ketorolac works well, it is not necessarily superior to other pain relievers. Morphine, the other treatment option in this trial, is a strong painkiller often used for severe pain and is known for its effectiveness, but it can have more side effects. The study aims to determine if Ketorolac, which has fewer side effects, is as effective as Morphine for treating stomach pain in children. ^{1 2 3 5 6}

Who Is on the Research Team?

Mohamed Eltorki, MBChB

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

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

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.

My abdominal pain has lasted 5 days or less.

Exclusion Criteria

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

Previous enrollment in the trial

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac
• Morphine

Trial Overview 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.

How Is the Trial Designed?

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, 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

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

In a study of 92 children aged 3 to 12, both intravenous morphine and ketorolac effectively provided pain relief for moderate to severe postsurgical pain, with morphine requiring fewer doses for analgesia.

While morphine provided quicker pain relief, ketorolac offered a longer duration of analgesia and was associated with fewer side effects, making it a viable alternative for managing pain in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intravenous ketorolac with morphine for postoperative pain in children. Maunuksela, EL., Kokki, H., Bullingham, RE.[2019]

In a study involving 176 postoperative patients, ketorolac (10 mg orally) provided analgesic efficacy comparable to both 5 mg and 10 mg doses of morphine, significantly outperforming placebo.

Ketorolac is a safe and effective option for managing acute postoperative pain, serving as a non-opioid alternative to traditional opioid therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ketorolac in the management of postoperative pain. DeAndrade, JR., Maslanka, M., Maneatis, T., et al.[2022]

Ketorolac tromethamine is an effective injectable nonsteroidal anti-inflammatory drug for acute pain management, showing analgesic potency comparable to morphine without the risk of respiratory depression or abuse potential.

It has a longer duration of action than morphine and is safer for patients since it has less impact on the central nervous system, although it is not recommended for use in obstetric analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac: an injectable NSAID. DiPalma, JR.[2013]

In a study involving 155 patients, ketorolac tromethamine was found to provide better pain relief than morphine sulfate at lower doses (30 and 90 mg) for moderate to severe postoperative pain, especially after the first hour.

Ketorolac demonstrated a favorable safety profile, with no serious side effects reported, while morphine was associated with somnolence in 8% of patients, highlighting ketorolac as a safe and effective alternative for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. O'Hara, DA., Fragen, RJ., Kinzer, M., et al.[2022]

In a study involving 51 patients with moderate to severe cancer pain, ketorolac tromethamine and morphine showed no significant difference in overall analgesic efficacy, indicating that ketorolac can be an effective alternative for pain management.

While 57% of patients on ketorolac and 74% on morphine changed their analgesic, significantly more patients discontinued ketorolac due to inadequate pain relief, whereas more patients stopped morphine due to side effects like nausea, suggesting ketorolac has a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative-study of intramuscular ketorolac tromethamine and morphine in patients experiencing cancer pain. Jameel, A., Stein, R., Rawson, N., et al.[2019]

This pilot trial aims to assess the feasibility of comparing the effectiveness of ketorolac and morphine for treating acute abdominal pain in children suspected of having appendicitis, with a target enrollment of 100 participants and a consent rate of at least 40%.

The study is designed as a double-dummy randomized controlled trial, ensuring that both participants and clinicians are blinded to the treatment, which will help provide reliable data on the safety and efficacy of these analgesics in a pediatric emergency setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketorolac versus morphine in children presenting with suspected appendicitis: a pilot single-centre non-inferiority randomised controlled trial. Eltorki, M., Busse, JW., Freedman, SB., et al.[2022]

In a study involving 120 children aged 2-10 years undergoing dental surgery, intravenous ketorolac at doses of 0.75, 1.0, and 1.5 mg/kg was found to be as effective as morphine (0.1 mg/kg) for pain relief.

Ketorolac significantly reduced the incidence of postoperative vomiting compared to morphine, making it a safer alternative for pediatric analgesia in this context.

NCBI (Pubmed)

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. Purday, JP., Reichert, CC., Merrick, PM.[2018]

In a study of 27 pediatric patients undergoing orthopedic surgeries, ketorolac significantly reduced the need for morphine compared to a control group, indicating its effectiveness in managing postoperative pain.

Patients receiving ketorolac experienced fewer gastrointestinal side effects and had a shorter hospital stay, demonstrating that it is a safe alternative to morphine for pain management in pediatric orthopedic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient. Eberson, CP., Pacicca, DM., Ehrlich, MG.[2013]

In a study involving 131 children aged 4-17 years with suspected fractures or dislocations, both sublingual ketorolac and tramadol significantly reduced pain, with mean pain scores dropping from eight to four for ketorolac and five for tramadol after 100 minutes.

There were no significant differences in pain relief or adverse effects between the two medications, indicating that both are equally effective for managing pain in pediatric patients with extremity injuries.

NCBI (Pubmed)

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. Neri, E., Maestro, A., Minen, F., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11996980/

Ketorolac use in the emergency department in children The systematic review highlights that ketorolac seems effective for managing acute pain in pediatric ED patients, but not superior to other analgesic drugs.

2. researchprotocols.org researchprotocols.org/2025/1/e76554

Comparison of Ketorolac at 3 Doses in Children With Acute ... The secondary hypothesis is that ketorolac 0.5 mg/kg up to 10 mg will be superior to 0.25 mg/kg up to 30 mg by at least the minimally important ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05641363

Comparison of Ketorolac at Three Doses in Children With ... Primary Outcomes: Between each low-dose ketorolac group and standard group mean differences in pain as measured on VNRS at 60 minutes. Summary: Acute pain ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12550451/

Comparison of Ketorolac at 3 Doses in Children With Acute Pain Emerging evidence, only applicable to adults, suggests that low-dose ketorolac (10 mg) is as effective as standard dose (30 mg) in acute pain management [5,9-11] ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06160778

Intravenous Ketorolac Vs. Morphine In Children With Acute ... 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.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40326658/

Ketorolac as an Analgesic in Pediatric Acute Pain ... Conclusions: Ketorolac appears to be a safe and effective option for managing acute pain in the pediatric population. The results indicate ...