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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether indomethacin or ketorolac better prevents post-ERCP pancreatitis (PEP) in children and young adults. PEP is a painful condition that can occur after an ERCP procedure, which some people need for their pancreas or bile ducts. Participants will receive either rectal indomethacin (an NSAID) or IV ketorolac (an NSAID given by injection) to assess which drug is more effective. This trial suits individuals aged 6 months to 21 years who are scheduled for an ERCP and have not recently used NSAIDs. As a Phase 4 trial, the research involves FDA-approved treatments and seeks to understand their benefits for more patients.

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 is the safety track record for these treatments?

Research has shown that rectal indomethacin is generally well-tolerated. In one study, only 4.4% of high-risk patients who received indomethacin developed moderate to severe pancreatitis after an ERCP procedure, a relatively low rate. It can be safely used for up to 48 hours, although it might not lower some inflammation markers in the body.

Studies have also shown that IV ketorolac is safe and can reduce the risk of pancreatitis after ERCP in high-risk patients. Ketorolac may also aid recovery by allowing patients to eat sooner and shortening hospital stays in severe pancreatitis cases.

Both treatments have a strong safety record for preventing pancreatitis after ERCP. Their approval for other uses means their safety is well understood. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for pancreatitis because they offer unique delivery methods and potential benefits. Rectal indomethacin is administered rectally, which might enhance pain relief with fewer systemic side effects compared to traditional oral medications. IV ketorolac, on the other hand, provides rapid pain relief through intravenous administration, potentially offering quicker and more effective management of acute pancreatitis pain than oral options. Both treatments rely on anti-inflammatory mechanisms but through different administration routes, which could optimize treatment based on patient needs and conditions.

What evidence suggests that this trial's treatments could be effective for preventing post-ERCP pancreatitis?

This trial will compare the effectiveness of rectal indomethacin and IV ketorolac for pancreatitis. Research has shown that rectal indomethacin effectively reduces the likelihood and severity of post-ERCP pancreatitis (PEP). In one study, only 4.4% of patients using rectal indomethacin developed moderate or severe PEP, compared to 8.8% of those who did not. Other studies also support indomethacin's effectiveness in preventing PEP.

For ketorolac, research suggests it might aid in severe acute pancreatitis by improving patients' ability to eat and shortening hospital stays. However, less information is available on ketorolac's effectiveness specifically for preventing PEP. Both treatments show promise, but stronger evidence supports indomethacin for preventing PEP. Participants in this trial will receive either rectal indomethacin or IV ketorolac to evaluate their effectiveness in this context. ^{1 3 4 6 7}

Who Is on the Research Team?

David Vitale, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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 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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34996820/

Ketorolac and Predicted Severe Acute Pancreatitis The use of ketorolac may improve feeding outcomes and shorten length of hospitalization in predicted severe acute pancreatitis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9242735/

Ketorolac and Predicted Severe Acute Pancreatitis The use of ketorolac may improve feeding outcomes and shorten length of hospitalization in predicted severe acute pancreatitis.

3. clinmedres.org clinmedres.org/content/early/2022/01/06/cmr.2021.1663

Ketorolac and Predicted Severe Acute Pancreatitis Conclusion: The use of ketorolac may improve feeding outcomes and shorten length of hospitalization in predicted severe acute pancreatitis.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X23000436

Effects of ketorolac on complications and postoperative ... Ninety-six (21%) patients were diagnosed with POPF within 30 days. There was a significant association between ketorolac use and clinically relevant POPF (21.4 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04282200

NCT04282200 | Ketorolac in Acute Pancreatitis This study will compare pain management strategies for patients hospitalized with acute pancreatitis.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34321424/

Ketorolac Is Safe and Associated With Lower Rate of Post- ... Pediatric patients undergoing ERCP with manipulation of the pancreatic duct are high risk for PEP, and ketorolac was associated with a lower rate of PEP in ...

7. giejournal.org giejournal.org/article/S0016-5107(20)33223-5/fulltext

Mo1982 INTRAPROCEDURAL KETOROLAC IS SAFE ... However, in high risk patients with manipulation of the pancreatic duct, ketorolac was associated with a significantly lower rate of PEP. Ketorolac was safe ...