Indomethacin vs Ketorolac for Pancreatitis
Recruiting in Palo Alto (17 mi)
Overseen byDavid Vitale, MD
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: David Vitale MD
Must not be taking: NSAIDs, Lithium
Disqualifiers: < 10 kg, Peptic ulcer, others
No Placebo Group
Prior Safety Data
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.
12345Is 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.
25678How 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.
24579Eligibility 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.
+9 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Rectal indomethacinExperimental Treatment1 Intervention
Dosage based on subject's weight:
\>=50 kg, 100 mg; 30-49 kg, 50 mg; 10-29 kg, 25 mg
Group II: IV ketorolacExperimental Treatment1 Intervention
Dosage based on subject's weight: 0.5 mg/kg (maximum: 15 mg)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cincinnati Children's Hospital Medical CenterCincinnati, OH
Loading ...
Who Is Running the Clinical Trial?
David Vitale MDLead Sponsor
David VitaleLead Sponsor
References
Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. [2013]The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo.
A comparison of intramuscular ketorolac with indomethacin suppositories in the treatment of pain after oral surgery. [2019]The analgesic effects of 30 mg intramuscular ketorolac were compared with those of rectal indomethacin in 100 mg and 200 mg doses in 66 patients in a single-blinded trial. Pain scores and the incidence of nausea and vomiting were assessed at 30, 60 and 120 minutes postoperatively, at discharge (4 hours) and on the evening of surgery. Area under the curve of pain scores versus time for pain at 30, 60 and 120 minutes postoperatively was significantly lower in the ketorolac group compared to indomethacin 100 mg and 200 mg groups. There were no significant differences in the pain scores at discharge or at home on the evening of surgery. At 60 minutes postoperatively there was significantly more nausea and vomiting in the indomethacin 200 mg group; at all other time-points there was no significant difference between the groups with regard to nausea and vomiting. The power of the study to determine the significance of side-effects between the groups was low.
A comparison of intramuscular ketorolac and pethidine in the alleviation of renal colic. [2022]To compare the analgesic efficacy of a single 30 mg intramuscular dose of ketorolac with that of intramuscular pethidine 100 mg, in a double-blind, parallel-group investigation of patients presenting with pain suggestive of renal colic.
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]Intravenous (IV) opioid titration is an accepted method of relieving acute renal colic. Studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) are also effective in this setting. Our objective was to compare single-dose ketorolac and titrated meperidine, both administered intravenously, with respect to speed and degree of analgesia, adverse effects and functional status. Our primary hypothesis was that these agents provide equivalent analgesia within 60 minutes. Our secondary hypotheses were that ketorolac-treated patients would experience fewer adverse effects and would be better able to resume usual activity.
Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic. [2022]To compare the analgesic efficacy and safety of IV ketorolac, the only nonsteroidal antiinflammatory drug indicated for parenteral use in acute pain in the United States, with IV meperidine and with a combination of the two agents in renal colic.
Minimising the adverse effects of ketorolac. [2018]Gastrointestinal bleeding and perforation, platelet inhibition with altered haemostasis, and renal impairment are among the list of adverse effects associated with the administration of ketorolac. The incidence of serious adverse events has declined since dosage guidelines were revised. Most of the published literature suggests that the overall risk of gastrointestinal or operative site bleeding related to ketorolac therapy is only slightly higher than with opioids. The risk for adverse events, however, increases with high doses, with prolonged therapy (>5 days) or in vulnerable patients (e.g. the elderly). Acute renal failure has been reported after ketorolac treatment but is usually reversible after discontinuation of the drug. As with other nonsteroidal anti-inflammatory drugs (NSAIDs), ketorolac may trigger allergic or hypersensitivity reactions. Careful patient selection is essential if use of ketorolac is considered. Contraindications to ketorolac use include a history of, or current risk of, gastrointestinal bleeding, risk of renal failure, compromised haemostasis, hypersensitivity to aspirin (acetylsalicylic acid) or other NSAIDs, labour, delivery and nursing. Ketorolac should be prescribed at the lowest dosage necessary to control pain; the duration of therapy should also be limited to as few days as possible. Practitioners should be familiar with, and follow, label warnings and dosage guidelines.
Ketorolac Is Safe and Associated With Lower Rate of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children With Pancreatic Duct Manipulation. [2023]Use of non-steroidal anti-inflammatory drugs (NSAIDs) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prevention in pediatrics is not well studied. Because of difficulty in accurately dosing indomethacin suppositories in pediatric patients, our center has used intravenous ketorolac for PEP prevention and present data on its safety and associated PEP rates.
Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. [2022]Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative pain. The 155 patient participants received single intramuscular doses of either ketorolac, 10, 30, or 90 mg, or morphine, 6 or 12 mg, administered in a double-blind, randomized fashion. Pain scores (verbal and visual analog) were recorded at baseline and assessed at 30 minutes and then hourly to 6 hours. Pain relief was rated at the same times. Ketorolac, 90 and 30 mg, was rated significantly better than morphine, 6 mg, at each assessment interval after 1 hour. Ketorolac, 90 and 30 mg, was rated similarly to morphine, 12 mg, for the first 3 hours and better than morphine, 12 mg, 4 hours after injection. There were no serious side effects reported. The only side effect reported in more than 3% of patients was 8% somnolence with morphine. This study shows ketorolac to be a safe and effective analgesic for relief of postoperative pain.
Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. [2019]To compare the analgesic efficacy and tolerability of intravenous (IV) ketorolac tromethamine with IV meperidine in the treatment of biliary colic, a prospective, randomized, double blind study was carried out upon a convenience sample of patients at a large inner city facility. Patients between the ages of 18 and 65 years of age with a history and physical examination consistent with biliary colic were enrolled over a 2-year period. Patients were randomly assigned to receive ketorolac 30 mg IV or meperidine 50 mg IV. Pain was quantified using a 4-point verbal rating system (VRS) as well as a visual analog scale (VAS). Patients were queried about their pain at times 0, 12 h, 1 h, and 2 h after administration of the study medication. Adverse effects were also recorded. A total of 324 patients completed the study protocol with 175 patients receiving ketorolac and 149 receiving meperidine. Patient demographics were similar for both groups with mean age for the ketorolac group of 36.1 years and for the meperidine group of 34.6 years. Both groups were predominantly Latino and over 80% of patients in both groups were female. No significant difference in pain control was found between ketorolac and meperidine in either the VAS or VRS for any time interval studied. The mean change in the VAS at time 2 h was 6.2 cm +/- 3.6 cm for the ketorolac group, compared with 6.7 cm +/- 3.6 cm for the meperidine group (p = 0.25). Although no significant difference was found in overall drug tolerability, patients receiving meperidine reported higher incidences of nausea and of dizziness than those receiving ketorolac (p = 0.009 and 0.003, respectively). Ketorolac tromethamine is a well-tolerated, effective medication in the treatment of acute biliary colic. It showed similar efficacy to meperidine with a decreased number of adverse effects.