Ketorolac Dosing for Acute Pain in Children

(KETODOSE Trial)

Recruiting at 1 trial location

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Opioids, Daily analgesics

Disqualifiers: Cognitive impairment, Gastrointestinal bleed, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 hours

171 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective dose of Ketorolac Tromethamine, a non-opioid pain medicine, for children in pain. Researchers seek to discover if smaller doses can relieve pain as effectively as the current standard dose. Children aged 6-17 who experience moderate to severe pain and are in the hospital or emergency department might be suitable candidates. The trial will compare different doses to identify which works best with the fewest side effects. This research could help doctors worldwide treat children's pain more safely. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for children's pain.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you use daily pain relievers, you cannot participate in the trial.

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

Research has shown that Ketorolac effectively manages pain in children and can serve as a good alternative to opioids. It eases moderate to severe pain, such as post-surgical or injury-related pain, making it a promising option for quick relief.

Ketorolac is generally well-tolerated for short-term use, meaning children usually do not experience significant side effects when taking it for a few days. However, its safety in children has not been studied as extensively as in adults. While not officially approved for long-term use in children, it is sometimes used off-label for short-term pain relief.

Adult studies have reported side effects like stomach pain, nausea, and headaches, though these are less common with short-term use. Since this study is in a later phase, it suggests earlier research has demonstrated some level of safety for Ketorolac in children. The study aims to find the best dose for children to ensure safety and effectiveness, acknowledging that some unknowns remain.

Overall, Ketorolac is considered safer than opioids due to fewer serious side effects and a lack of addictive properties. This study will help determine the smallest effective dose of Ketorolac to minimize the chance of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of ketorolac tromethamine for acute pain in children because it offers a potentially effective alternative to opioids, which are commonly used but come with significant risk of addiction and side effects. Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that works by reducing inflammation and pain without the addictive properties of opioids. Unlike other pain relief options, this study explores different dosing strategies, possibly allowing for effective pain management with lower doses, which could minimize potential side effects. This approach could provide a safer, non-opioid option for managing acute pain in children, which is a significant advancement in pediatric pain management.

What evidence suggests that Ketorolac might be an effective treatment for acute pain in children?

Research shows that ketorolac effectively manages sudden pain in children. Studies indicate that ketorolac performs as well as other pain medicines often used in emergency rooms. This trial will compare different dosing strategies of ketorolac. New findings from adult studies suggest that a lower dose of ketorolac can be as effective as a higher dose for pain relief. This suggests children might achieve pain relief with less medication, reducing the risk of side effects. Although most information comes from adult studies, ketorolac is considered safer than opioids, which can have serious side effects. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children aged 6 to less than 18 experiencing moderate to severe acute pain, who are in the emergency department or hospitalized with an IV line already in place. It's not for kids with chronic kidney or liver diseases, those who've taken ketorolac or opioids recently, have a history of bleeding disorders, known pregnancy, NSAID or opioid allergies, cognitive impairments that prevent consent, or are post-operative.

Inclusion Criteria

Patient with IV cannula in situ or ordered

I have been experiencing acute pain for less than 30 days.

I am between 6 and 18 years old and have moderate to severe pain.

Exclusion Criteria

I have recently used ketorolac or opioids.

Inability to obtain consent

Either I or my child has cognitive impairment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive one of three doses of IV Ketorolac, with pain and adverse events monitored over 8 hours

8 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 days

1 follow-up survey (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac Tromethamine

Trial Overview The study tests three different doses of Ketorolac Tromethamine—a non-opioid painkiller—to find the smallest effective dose for children's pain relief without unnecessary side effects. Participants will be randomly assigned to receive one of two smaller doses or the normal dose used at MCH and will be monitored over two hours for pain levels and additional medication needs.

How Is the Trial Designed?

Group I: Low dose group B2 Experimental Treatment 1 Intervention

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

Group II: Low dose group B1 Experimental Treatment 1 Intervention

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

Group III: Standard dose group A Active Control 1 Intervention

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

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

Approved in United States as Toradol for:

• Moderate to severe pain
• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Menstrual disorders
• Headaches

Approved in European Union as Ketorolac for:

• Moderate to severe pain
• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Menstrual disorders
• Headaches

Approved in Canada as Ketorolac for:

• Moderate to severe pain
• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Menstrual disorders
• Headaches

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory drug (NSAID) for managing moderate to severe postoperative pain, reducing the need for opioid analgesics, which can help minimize opioid-related side effects.

Administered intramuscularly, ketorolac reaches peak plasma levels in about 45 to 50 minutes and has a low incidence of side effects, making it a promising option for both inpatient and outpatient pain management, although further research is needed to fully understand its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. Lassen, K., Epstein-Stiles, M., Olsson, GL.[2013]

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 multicenter study involving patients with moderate to severe inflammation after cataract surgery, ketorolac tromethamine 0.5% was significantly more effective than a placebo in reducing inflammation and associated symptoms like pain and photophobia.

The treatment was found to be safe, with no significant differences in visual acuity or adverse events compared to the placebo, indicating that ketorolac is a reliable option for managing post-surgical inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. Heier, J., Cheetham, JK., Degryse, R., et al.[2019]

In a study involving 24 children with advanced HIV infection, didanosine showed similar bioavailability when administered at a once-daily dose of 180 mg/m² compared to a twice-daily dose of 90 mg/m².

The relative bioavailability of didanosine was found to be 0.95 ± 0.49, suggesting that once-daily dosing could be clinically effective for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of once- and twice-daily regimens of didanosine in human immunodeficiency virus-infected children. Abreu, T., Plaisance, K., Rexroad, V., et al.[2021]

In a study involving 40 patients with severe odontogenic pain, ketorolac tromethamine (KT) significantly reduced pain levels compared to a placebo, with patients reporting negligible discomfort by 90 minutes post-injection.

KT effectively alleviates severe pain within 40 minutes of administration, demonstrating its efficacy as an analgesic with minimal side effects, such as lightheadedness and injection site pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of ketorolac tromethamine for control of severe odontogenic pain. Curtis, P., Gartman, LA., Green, DB.[2013]

A case study of a 31-year-old man revealed that excessive use of ketorolac tromethamine (Acula) after PRK led to corneal ulceration and perforation, necessitating surgical intervention.

The findings highlight the importance of proper patient education regarding the use of topical NSAIDs post-surgery to prevent complications like corneal damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal ulceration and perforation with ketorolac tromethamine (Acular) use after PRK. Mian, SI., Gupta, A., Pineda, R.[2019]

In a study involving 200 patients undergoing photorefractive keratectomy, topical ketorolac tromethamine 0.5% was found to provide significantly greater pain relief compared to its vehicle, with patients experiencing less pain intensity and a longer time before needing additional pain medication.

The ketorolac group also reported fewer side effects, such as sleep difficulties and ocular discomfort, and overall, the treatment was deemed safe with minimal adverse events, indicating its efficacy and safety for post-surgery pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group. Rajpal, RK., Cooperman, BB.[2022]

In a study involving 55 adolescents with HIV-1, doravirine and the fixed-dose combination (DOR FDC) of doravirine/lamivudine/tenofovir disoproxil fumarate demonstrated effective pharmacokinetics similar to those seen in adults, indicating its potential for use in this age group.

The treatment was well-tolerated, with no serious drug-related adverse events, and 93.3% of participants maintained undetectable HIV-1 RNA levels (<40 copies/mL) after 24 weeks, showcasing its efficacy in managing HIV-1 in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Week 24 Results From IMPAACT 2014. Melvin, AJ., Yee, KL., Gray, KP., et al.[2023]

In a study of 318 HIV-infected children and adolescents, 69% received off-label antiretroviral (ARV) medications, primarily due to treatment failure, highlighting the commonality of off-label use in pediatric HIV treatment.

Incorrect dosing was prevalent, with 10% of patients either overdosed or underdosed; notably, underdosing was linked to a significantly higher rate of treatment failure (50% vs. 26% for overdosed patients), emphasizing the need for careful dosing and suitable formulations for younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Description and consequences of prescribing off-label antiretrovirals in the Madrid Cohort of HIV-infected children over a quarter of a century (1988-2012). Fernández-Cooke, E., Rojas, P., Holguin, A., et al.[2016]

Lamivudine, an antiretroviral medication, was well-tolerated in a study of 90 HIV-infected children, showing significant decreases in HIV RNA levels and stable CD4 and CD8 cell counts over 24 weeks.

While lamivudine demonstrated virologic activity, some patients developed resistance to the drug by 12 weeks, suggesting that it may be more effective when used in combination with other antiretroviral therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group. Lewis, LL., Venzon, D., Church, J., et al.[2019]

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]

Ketorolac tromethamine is effective for treating moderate to very severe postoperative pain, with oral doses of 10 mg and higher showing significant superiority over placebo and comparable efficacy to morphine.

The drug is well tolerated, with fewer adverse events compared to opioid pain relievers, making it a safer alternative for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy and safety of single-dose oral and intramuscular ketorolac tromethamine for postoperative pain. Brown, CR., Moodie, JE., Dickie, G., et al.[2013]

A standardized drug dosage table for antiretroviral treatment (ART) was found to be highly acceptable among doctors, with 94% of surveyed physicians reporting it made prescribing easier and reduced calculation errors.

In a study of 49 children prescribed ARVs, less than 5% experienced adverse side effects, and all ARV-naïve children achieved undetectable viral loads within six months, demonstrating the safety and efficacy of the standardized dosing approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A drug dosage table is a useful tool to facilitate prescriptions of antiretroviral drugs for children in Thailand. Ponnet, M., Frederix, K., Petdachai, W., et al.[2019]

Citations

1. 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] ...

2. 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.

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

Comparison of Ketorolac at Three Doses in Children With ... Despite data in adults and children supporting preferential NSAID use for acute pain, significant gaps in knowledge regarding safe and effective Ketorolac ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02973958

Evaluating Pain Outcomes of Ketorolac Administration in ... This study aims to see if giving ketorolac during the operation will result in better pain control.

5. annemergmed.com annemergmed.com/article/S0196-0644(23)00298-6/abstract

Comparative Effectiveness of Ketorolac Dosing Strategies ... Further, low-dose ketorolac at 10 mg may have no effect on pain scores compared to high-dose ketorolac (mean difference 1.58 mm lower on 100 mm ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK545172/

Ketorolac - StatPearls - NCBI Bookshelf In children, ketorolac is as effective as major opioid analgesics.[2] Thus, this drug is a great pain management alternative or adjunct for pediatric (off-label ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/ketorolac-oral-route-injection-route/description/drg-20066882

Ketorolac (oral route, injection route) - Side effects & dosage Ketorolac is used to relieve moderately severe pain, usually pain that occurs after an operation or other painful procedure.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/019645s019lbl.pdf

TORADOL (ketorolac tromethamine tablets) Rx only ... is not indicated for use in pediatric patients. The safety and effectiveness of TORADOL. ORAL in pediatric patients below the age of 17 have not been ...

9. reference.medscape.com reference.medscape.com/drug/ketorolac-343292

Ketorolac dosing, indications, interactions, adverse effects, ... Short-term (≤5 days) management of moderately severe acute pain that requires analgesia at opioid level; not indicated for minor or chronic painful conditions.

10. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=4487

Ketorolac Tromethamine Ketorolac tromethamine is not indicated for use in pediatric patients and it is NOT indicated for minor or chronic painful conditions. Increasing the dose of ...