Ketorolac for Postoperative Pain in Pediatric Heart Surgery

(CIVIK Trial)

Overseen By Samantha Stack, BS

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Phoenix Children's Hospital

Must not be taking: NSAIDs

Disqualifiers: Acute kidney injury, ECMO, others

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: Unknown

Duration: 48 hours

166 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how different methods of administering ketorolac, a pain relief medication, affect the need for opiates after pediatric heart surgery. Researchers aim to determine if a continuous infusion of ketorolac reduces the use of stronger painkillers compared to intermittent dosing. The trial includes two groups: one receives a steady flow of ketorolac, while the other receives it intermittently, the usual method. Children who have recently undergone heart surgery and are staying in the cardiovascular ICU might be suitable participants, provided they do not have specific kidney issues or allergies to the medication. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

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

The trial protocol does not specify if you need to stop taking your current medications. However, since the trial involves ketorolac, you should discuss your current medications with the trial team to ensure there are no interactions.

What is the safety track record for ketorolac?

Research has shown that ketorolac can be safe for children after heart surgery. Studies found that administering ketorolac every 6 hours for up to 48 hours did not cause kidney problems or bleeding in newborns post-surgery. Another study suggested ketorolac is well-tolerated when used after heart surgery in general. Although a warning exists about its use, evidence indicates it can be effective without causing major issues. However, limited data on all safety outcomes means some caution is still advised. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for postoperative pain in pediatric heart surgery, like standard NSAIDs, are given intermittently and require higher doses to be effective. But ketorolac in this study is different because it is administered continuously at a lower dose. This approach aims to manage pain more effectively while minimizing potential side effects associated with higher doses of NSAIDs. Researchers are excited about this treatment because it could offer a safer, more consistent pain management option for young heart surgery patients.

What evidence suggests that this trial's treatments could be effective for postoperative pain in pediatric heart surgery?

Research has shown that ketorolac reduces pain after surgery. In this trial, participants in the treatment arm will receive a continuous infusion of ketorolac. Studies have found that this leads to lower pain levels compared to not using it. This often results in a reduced need for opioid painkillers, a significant advantage. Importantly, patients who received ketorolac did not experience more kidney problems, which is crucial for safety. Overall, evidence suggests that ketorolac effectively manages pain after heart surgery. ^{4 6 7 8 9}

Who Is on the Research Team?

Kevin Engelhardt, MD

Principal Investigator

Heart Center

Are You a Good Fit for This Trial?

This trial is for children aged 3 months to 4 years who have had heart surgery and are in the pediatric cardiovascular ICU. They must start the study medication within two days after surgery. Kids with NSAID allergies, recent heart transplants, significant bleeding, kidney injuries or needing intensive support like ECMO or CRRT can't participate.

Inclusion Criteria

My child is between 3 months and 4 years old and was admitted to the CVICU after surgery.

I started the study medication within 48 hours after surgery.

Exclusion Criteria

I have had serious bleeding issues recently.

I needed heart or kidney support machines right after surgery.

You have had a bad reaction to ketorolac or other similar pain medications in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either continuous infusion of ketorolac or intermittent ketorolac for postoperative pain control

48 hours

Continuous monitoring in CVICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain scores and sedative requirements

4 days

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac

Trial Overview The study is testing if giving ketorolac continuously through an IV works better for pain control than giving it in separate doses (intermittently) after pediatric heart surgery. It's a controlled experiment where neither doctors nor patients know who gets which treatment to fairly compare outcomes.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

1. Description: Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte). To eliminate excess exposure and the associated side effects, all patients enrolled in the study will not be given any additional NSAIDs (except aspirin, which is standard of care in many post-operative cardiac surgery patients) during the study period. 2. Dosage and Route of Administration: 1. Continuous ketorolac 0.08mg/kg/hr, with a maximum of 5mg/hr for patients weighing greater than or equal to 60kg, administered intravenously by nursing staff. Study drug will infuse continuously for 48 hours. 2. Intermittent Plasmalyte 0.033mL/kg (max 2mL) infusion every 6 hours for 48 hours.

Group II: Standard of care Placebo Group 1 Intervention

1. Description: Patients randomized to the standard of care arm of the study will receive a generically marked syringe of Plasmalyte to be infused at the same rate as the treatment medication, and will only receive intermittent dosing of ketorolac (current standard of care). As in the treatment group, no additional NSAIDs (except aspirin) are to be given during the 48 hour study period. 2. Dosage and Route of Administration 1. Continuous Plasmalyte infusion to match the aforementioned ketorolac dosing 2. Intermittent ketorolac 0.5mg/kg IV infusion every 6 hours (max 30mg per dose)

Who Is Running the Clinical Trial?

Phoenix Children's Hospital

Lead Sponsor

Trials

78

Recruited

5,014,000+

Published Research Related to This Trial

In a study of 248 children who underwent low-risk cardiac surgery, ketorolac did not significantly affect renal function, as indicated by similar changes in serum creatinine levels between those who received ketorolac and those who did not.

Children who received ketorolac post-surgery required less opioid medication for pain management compared to the control group, suggesting that ketorolac may effectively reduce opioid use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ketorolac in children after cardiac surgery. Inoue, M., Caldarone, CA., Frndova, H., et al.[2021]

In a retrospective study of breast surgery patients over three years, ketorolac did not significantly increase the risk of postoperative hematoma formation, with rates of 3.5% in those receiving ketorolac compared to 2.5% in those who did not.

The overall hematoma rate for the entire cohort was 2.8%, suggesting that ketorolac can be safely used for postoperative pain control without raising concerns about bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? Nguyen, BN., Barta, RJ., Stewart, CE., et al.[2021]

In a study involving 70 infants and children who underwent congenital heart surgery, ketorolac was found to effectively manage postoperative pain without increasing the risk of bleeding complications compared to opioid analgesics alone.

The results showed that patients receiving ketorolac had lower median chest-tube drainage and no significant wound bleeding, indicating its safety and efficacy as a pain management option in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized trial of ketorolac after congenital heart surgery. Gupta, A., Daggett, C., Drant, S., et al.[2019]

In a study of 127 patients undergoing major surgery, intranasal ketorolac at a dose of 31.5 mg significantly reduced the need for supplemental morphine compared to placebo and the lower 10 mg dose, indicating its efficacy in managing postoperative pain.

The 31.5 mg dose of ketorolac also resulted in lower rates of pyrexia and tachycardia compared to placebo, suggesting a better safety profile while effectively controlling pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. Moodie, JE., Brown, CR., Bisley, EJ., et al.[2013]

A study reviewing 842 infants and children who underwent congenital heart surgery found that postoperative use of ketorolac did not significantly increase the risk of bleeding complications, with 0% of ketorolac patients requiring surgical exploration compared to 4.2% in the non-ketorolac group.

The relative risk of postoperative bleeding requiring surgical intervention in patients receiving ketorolac was 0.2, indicating that ketorolac can be safely used without a significant increase in bleeding risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac after congenital heart surgery: does it increase the risk of significant bleeding complications? Gupta, A., Daggett, C., Ludwick, J., et al.[2013]

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]

A single dose of ketorolac significantly prolonged bleeding times and reduced platelet aggregation in a rat model, indicating its strong anti-thrombotic effects immediately after administration.

Despite its initial effectiveness in preventing thrombosis, ketorolac was ineffective for long-term prevention of microarterial thrombosis, and its use may pose a risk of bleeding complications in postoperative patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketorolac tromethamine (Toradol) on a functional model of microvascular thrombosis. Buckley, RC., Davidson, SF., Das, SK.[2019]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19562323/

Safety and efficacy of ketorolac in children after cardiac ... The data suggest that ketorolac may be effective in reducing the exposure to opioids. Further studies are required to define subsets of children after cardiac ...

2. 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11023609/

Ketorolac Dosing and Outcomes in Neonates Following ... Findings: Ketorolac 0.5 mg/kg/dose every 6 hours for up to 48 hours in neonates following cardiac surgery did not result in renal impairment or ...

4. systematicreviewsjournal.biomedcentral.com systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-024-02685-z

The efficacy and safety of ketorolac for postoperative pain ... The results indicate that, compared to the control group, Ketorolac is associated with significantly lower postoperative pain scores within the ...

5. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/pdf/10.1111/cts.13907

Early administration of ketorolac after cardiac surgery and ... The matched cohort exhibited an 8.1% overall rate of postoperative complications, with a lower composite outcome rate in patients receiving ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6513208/

Ketorolac for postoperative pain in children - PMC However, as noted, there was insufficient evidence available for all efficacy and safety outcomes, with no data for one of our primary outcomes. Quality of ...

7. journals.lww.com journals.lww.com/ccejournal/fulltext/2024/04000/ketorolac_dosing_and_outcomes_in_neonates.17.aspx

Ketorolac Dosing and Outcomes in Neonates Following... Findings: Ketorolac 0.5 mg/kg/dose every 6 hours for up to 48 hours in neonates following cardiac surgery did not result in renal impairment or bleeding.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00161577

Use of Ketorolac in Management of Post-Operative Pain ... This study evaluates the safety and efficacy of ketorolac for post-operative pain management after heart surgery. Ketorolac appears to provide enhanced pain ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053077013004242

Is Ketorolac Safe for Use After Cardiac Surgery? Ketorolac appears to be well-tolerated for use when administered selectively after cardiac surgery. Although a black box warning exists, the data highlights ...