Indomethacin vs Ketorolac for Pancreatitis

Overseen By Ethan Estes

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: David Vitale MD

Must not be taking: NSAIDs, Lithium

Disqualifiers: < 10 kg, Peptic ulcer, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: Immediate (single administration)

192 Participants Needed

Trial Summary

What is the purpose of this trial?

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure that can be complicated by post-ERCP pancreatitis (PEP). Indomethacin and ketorolac are two medications used to prevent PEP. The main reason for this research study is to compare the effectiveness these drugs at reducing rates of PEP. There have been no studies comparing the effectiveness of these medications in preventing PEP in pediatric patients. You are being asked to take part in this research study because you are scheduled to have an ERCP as part of your medical care.

Will I have to stop taking my current medications?

The trial requires that you have not used NSAIDs (non-steroidal anti-inflammatory drugs) in the previous 5 days. If you are taking NSAIDs, you will need to stop them at least 5 days before participating.

What data supports the effectiveness of the drug for pancreatitis?

Research shows that ketorolac, a drug used in the trial, is effective in reducing pain and inflammation in various conditions, such as after surgery and in renal colic (severe kidney pain). It has been found to be more potent than other similar drugs, which suggests it might be effective for pancreatitis as well. ^{1 2 3 4 5}

Is the combination of Indomethacin and Ketorolac safe for treating pancreatitis?

Ketorolac can cause side effects like stomach bleeding, kidney issues, and allergic reactions, especially in high doses or long-term use. Indomethacin may cause nausea and vomiting, particularly at higher doses. Both drugs should be used carefully, following dosage guidelines, and are generally safe when used for short periods. ^{2 5 6 7 8}

How do indomethacin and ketorolac differ from other drugs for pancreatitis?

Indomethacin and ketorolac are nonsteroidal anti-inflammatory drugs (NSAIDs) that may offer a unique approach to treating pancreatitis by reducing inflammation, unlike traditional treatments that may focus more on pain relief. Ketorolac, in particular, has been used intravenously for pain management in other conditions, suggesting it might provide effective relief with potentially fewer side effects compared to opioids. ^{2 4 5 7 9}

Research Team

David Vitale, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for children and young adults aged 6 months to 21 years who are scheduled for an ERCP procedure. Participants must not have kidney disease, be pregnant, weigh less than 10 kg, or have a high bleeding risk. They should not have taken NSAIDs recently or have acute pancreatitis at the time of ERCP.

Inclusion Criteria

I am scheduled for or have had an ERCP procedure.

Does not meet exclusion criteria

I am between 6 months and 21 years old.

Exclusion Criteria

I haven't taken NSAIDs in the last 5 days.

I have organ dysfunction or a systemic inflammatory response.

I am currently on lithium therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either rectal indomethacin or intravenous ketorolac based on their weight to prevent post-ERCP pancreatitis

Immediate (single administration)

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of post-ERCP pancreatitis and pain

2 weeks

Multiple assessments during hospital stay

Treatment Details

Interventions

• IV Ketorolac
• Rectal Indomethacin

Trial Overview The study compares rectal indomethacin with IV ketorolac in preventing post-ERCP pancreatitis in pediatric patients. It's the first study of its kind in this age group and aims to determine which medication is more effective at reducing PEP rates after the procedure.

Participant Groups

Group I: Rectal indomethacin Experimental Treatment 1 Intervention

Dosage based on subject's weight: \>=50 kg, 100 mg; 30-49 kg, 50 mg; 10-29 kg, 25 mg

Group II: IV ketorolac Experimental Treatment 1 Intervention

Dosage based on subject's weight: 0.5 mg/kg (maximum: 15 mg)

Who Is Running the Clinical Trial?

David Vitale MD

Lead Sponsor

Trials

2

Recruited

250+

David Vitale

Lead Sponsor

Trials

1

Recruited

190+

Findings from Research

Ketorolac demonstrates significant analgesic efficacy compared to other NSAIDs, with its potency being similar across various pain models in rats, indicating a strong analgesic effect.

The unique pharmacokinetic properties of ketorolac, particularly its lower lipophilicity, may enhance the concentration of its active form, (S)-ketorolac, at biological targets, contributing to its superior efficacy in pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. Jett, MF., Ramesha, CS., Brown, CD., et al.[2013]

In a study of 66 patients, intramuscular ketorolac (30 mg) provided significantly better pain relief compared to rectal indomethacin (100 mg and 200 mg) at 30, 60, and 120 minutes post-surgery.

The 200 mg dose of indomethacin was associated with a higher incidence of nausea and vomiting at 60 minutes, suggesting that ketorolac may have a better safety profile regarding side effects in the early postoperative period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of intramuscular ketorolac with indomethacin suppositories in the treatment of pain after oral surgery. Turner, GA., Anson, N., Williamson, R.[2019]

In a study involving 76 patients treated with ketorolac and 78 with pethidine for renal colic, ketorolac demonstrated superior analgesic efficacy, with statistically significant pain reduction compared to pethidine (P < 0.05).

Ketorolac also had a lower incidence of adverse events (28%) compared to pethidine (51%), making it a safer alternative for pain management in renal colic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of intramuscular ketorolac and pethidine in the alleviation of renal colic. Sandhu, DP., Iacovou, JW., Fletcher, MS., et al.[2022]

In a multicenter trial involving 142 patients with moderate to severe renal colic, single-dose intravenous ketorolac provided pain relief comparable to titrated intravenous meperidine within 60 minutes.

Patients treated with ketorolac experienced significantly less functional impairment, with 44% able to resume usual activities compared to only 10% of those treated with meperidine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NARC (nonsteroidal anti-inflammatory in renal colic) trial. Single-dose intravenous ketorolac versus titrated intravenous meperidine in acute renal colic: a randomized clinical trial. Wood, VM., Christenson, JM., Innes, GD., et al.[2022]

In a study involving 154 patients with suspected renal colic, IV ketorolac was found to be significantly more effective than IV meperidine alone for pain relief, with 75% of the ketorolac group achieving a 50% reduction in pain within 30 minutes compared to only 23% in the meperidine group.

Both IV ketorolac alone and in combination with meperidine provided superior analgesia compared to meperidine alone, suggesting that clinicians may prefer starting treatment with ketorolac, either alone or combined, for better pain management in renal colic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic. Cordell, WH., Wright, SW., Wolfson, AB., et al.[2022]

Ketorolac can cause serious side effects like gastrointestinal bleeding and renal impairment, but the risk of these events has decreased since dosage guidelines were revised, making it slightly safer than opioids for pain management.

The risk of adverse effects increases with higher doses, prolonged use beyond 5 days, or in vulnerable populations such as the elderly, highlighting the importance of careful patient selection and adherence to prescribing guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimising the adverse effects of ketorolac. Reinhart, DI.[2018]

In a study of 298 pediatric patients undergoing ERCP, the use of intravenous ketorolac for preventing post-endoscopic retrograde cholangiopancreatography (PEP) was found to be safe, with no significant increase in bleeding rates compared to those who did not receive it.

For high-risk patients who had manipulation of the pancreatic duct, ketorolac significantly reduced the rate of PEP from 25% to 11%, suggesting it may be an effective preventive measure in this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac Is Safe and Associated With Lower Rate of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children With Pancreatic Duct Manipulation. Mark, JA., Kramer, RE.[2023]

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 of 324 patients with biliary colic, intravenous ketorolac was found to be as effective as intravenous meperidine for pain relief, with no significant differences in pain control measured by visual analog scale (VAS) or verbal rating system (VRS).

Ketorolac demonstrated better tolerability than meperidine, as patients receiving meperidine reported higher rates of nausea and dizziness, making ketorolac a preferable option for treating acute biliary colic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. Henderson, SO., Swadron, S., Newton, E.[2019]

References

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

Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. [2013]

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

A comparison of intramuscular ketorolac with indomethacin suppositories in the treatment of pain after oral surgery. [2019]

3. England pubmed.ncbi.nlm.nih.gov

A comparison of intramuscular ketorolac and pethidine in the alleviation of renal colic. [2022]

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

The NARC (nonsteroidal anti-inflammatory in renal colic) trial. Single-dose intravenous ketorolac versus titrated intravenous meperidine in acute renal colic: a randomized clinical trial. [2022]

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

Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Minimising the adverse effects of ketorolac. [2018]

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

Ketorolac Is Safe and Associated With Lower Rate of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children With Pancreatic Duct Manipulation. [2023]

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

Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. [2022]

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

Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. [2019]