Indomethacin for Preventing Acute Pancreatitis After EUS-FNA

Overseen By Barbara J Broome

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Orlando Health, Inc.

Must not be taking: Aspirin, NSAIDs

Disqualifiers: Pregnancy, Chronic pancreatitis, Renal failure, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether indomethacin, an anti-inflammatory medication, can prevent pancreatitis (inflammation of the pancreas) after a procedure called EUS-FNA. EUS-FNA examines pancreatic cysts, and pancreatitis can occur afterward. Participants will receive either indomethacin or a placebo (a harmless pill with no effect) to determine which is more effective. Individuals with suspected or confirmed pancreatic cysts who require EUS-FNA may qualify for this trial, provided they have no allergies to NSAIDs or a history of chronic pancreatitis.

As an unphased trial, this study offers a chance to contribute to medical knowledge and potentially benefit future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that indomethacin is likely to be safe for humans?

Research has shown that rectal indomethacin is generally safe for people. In past studies, patients used indomethacin to help prevent pancreatitis, which is inflammation of the pancreas, after certain medical procedures. Most people did not experience serious side effects.

One study used a dose of 100 mg, similar to this trial, and found it helped lower the risk of pancreatitis without causing major issues for patients. Common side effects were mild, such as stomach upset or minor discomfort in the rectal area.

Indomethacin is also approved by the FDA for other conditions, indicating its safety has been studied in different situations, which gives doctors more confidence in using it.

Overall, evidence supports that rectal indomethacin is safe when used as intended in these medical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for preventing acute pancreatitis after EUS-FNA, which often involves hydration and other supportive measures, indomethacin offers a unique approach by using an anti-inflammatory mechanism to potentially reduce inflammation quickly. Researchers are excited about indomethacin because it is administered rectally, allowing for direct and rapid absorption, which might enhance its effectiveness in preventing pancreatitis. This delivery method is expected to provide more immediate relief and potentially prevent the onset of acute symptoms, setting it apart from other conventional treatments.

What evidence suggests that indomethacin might be an effective treatment for preventing acute pancreatitis after EUS-FNA?

Research has shown that rectal indomethacin can lower the risk of pancreatitis, which is inflammation of the pancreas, after certain medical procedures. Studies have found that it reduces both the likelihood and severity of pancreatitis following procedures like ERCP, a type of endoscopy. In this trial, participants will receive either rectal indomethacin or a placebo after undergoing a different procedure called EUS-FNA. The researchers hope indomethacin will offer similar benefits in this context. By preventing inflammation, indomethacin could protect the pancreas from harm, making it a promising option for preventing pancreatitis after procedures. ^{1 2 3 6 7}

Who Is on the Research Team?

Ji Young Bang, MD MPH

Principal Investigator

Orlando Health, Digestive Health Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with suspected or confirmed pancreatic cysts needing EUS-FNA. It's not for those with chronic pancreatitis, pregnant women, people allergic to Aspirin/NSAIDs, or those with renal failure.

Inclusion Criteria

I have a pancreatic cyst that needs a biopsy.

Exclusion Criteria

Intrauterine pregnancy

Unable to obtain consent from the participant or the participant's legally authorized representative (LAR)

Hypersensitivity reaction to Aspirin or NSAIDs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of indomethacin or placebo administered rectally during EUS-FNA

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on post-procedure pancreatitis and other adverse events

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Indomethacin

Trial Overview The study tests if a single dose of indomethacin given rectally can prevent acute pancreatitis after EUS-FNA of pancreatic cysts compared to a placebo.

How Is the Trial Designed?

Group I: Rectal Indomethacin Active Control 1 Intervention

Patients assigned to the Indomethacin group will receive100 mg of indomethacin administered per rectal route (two tablets of 50 mg indomethacin suppositories)

Group II: Placebo Placebo Group 1 Intervention

Patients assigned to the Placebo group will receive two glycerin suppositories.

Who Is Running the Clinical Trial?

Orlando Health, Inc.

Lead Sponsor

Trials

32

Recruited

15,100+

Published Research Related to This Trial

A meta-analysis of 17 trials involving 4741 patients found that rectally administered diclofenac or indomethacin significantly reduced the risk of post-ERCP pancreatitis (PEP) by 40%, with a number needed to treat (NNT) of 20.

Both diclofenac and indomethacin were equally effective in preventing PEP, and no significant adverse events were reported, making these medications a safe and cost-effective option for patients undergoing ERCP, except in those with renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indomethacin and diclofenac in the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis of prospective controlled trials. Patai, Á., Solymosi, N., Mohácsi, L., et al.[2022]

In a study involving 1037 high-risk patients undergoing ERCP, increasing the dose of rectal indometacin to 200 mg did not significantly reduce the incidence of pancreatitis compared to the standard 100 mg dose, with pancreatitis occurring in 14% of patients overall.

The study found that while there were some adverse events related to the medication, including a small number of cases of clinically significant bleeding and acute kidney injury, there were no deaths or allergic reactions, suggesting that both dosing regimens were relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial. Fogel, EL., Lehman, GA., Tarnasky, P., et al.[2023]

In a randomized controlled trial involving 449 patients undergoing ERCP, rectal indomethacin did not significantly reduce the incidence of post-ERCP pancreatitis compared to a placebo, with rates of 7.2% in the indomethacin group and 4.9% in the placebo group (P = .33).

The study was stopped early due to futility, indicating that the use of rectal indomethacin as a preventive measure for pancreatitis in both high-risk and average-risk patients undergoing ERCP may not be effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients. Levenick, JM., Gordon, SR., Fadden, LL., et al.[2022]

Endoscopic retrograde cholangiopancreatography (ERCP) is commonly performed in Hungary, with about 1400 patients developing pancreatitis each year, highlighting the need for effective prevention strategies.

The authors recommend several preventive measures, including careful patient selection, minimizing cannulation attempts, using pancreatic stents in high-risk patients, and administering rectal indomethacin or diclofenac to reduce the risk of post-ERCP pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention of acute pancreatitis following endoscopic retrograde cholangiopancreatography]. Patai, Á., Patai, ÁV., Solymosi, N., et al.[2017]

In a study involving 2000 patients, the administration of 100 mg of diclofenac before ERCP did not reduce the incidence of post-ERCP pancreatitis (PEP), with rates remaining at 2.8% for both the diclofenac and control groups.

Diclofenac also showed no benefit in reducing the severity of PEP in high-risk patients, suggesting that routine use of this medication may not be effective in preventing pancreatitis in a low-risk ERCP setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units. Rainio, M., Lindström, O., Udd, M., et al.[2018]

Indomethacin suppositories, which are effective in preventing post-ERCP pancreatitis (PEP), were under-utilized in clinical practice, with usage remaining below 50% in 2018 despite evidence supporting their benefit.

The overall rate of PEP remained unchanged at 8.6% from 2009 to 2018, which may be linked to the low adoption of indomethacin and a significant decline in pancreatic duct stent usage during the same period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Practice Patterns in the Era of Rectal Indomethacin for Prophylaxis Against Post-ERCP Pancreatitis in a High-Risk Cohort. Smith, ZL., Elmunzer, BJ., Cooper, GS., et al.[2022]

In a study involving rats, rebamipide significantly reduced the area of stomach erosions caused by indometacin, suggesting its effectiveness as an anti-ulcer agent.

Rebamipide's protective effect is likely due to its antioxidant properties, which help inhibit lipid peroxidation in the gastric mucosa, thereby preventing gastric injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rebamipide on lipid peroxidation and gastric mucosal injury induced by indometacin in rats. Yoshikawa, T., Naito, Y., Nakamura, S., et al.[2022]

In a study of 372 patients undergoing ERCP, diclofenac and indomethacin were found to significantly reduce the incidence of post endoscopic retrograde cholangiopancreatography pancreatitis (PEP) compared to naproxen, with PEP rates of 4% and 5.8% respectively, versus 15.9% for naproxen.

Patients receiving diclofenac and indomethacin also showed increased levels of protective molecules (lipoxin A4 and resolvin E1), suggesting a potential mechanism for their effectiveness in preventing PEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of rectal indomethacin, diclofenac, and naproxen for the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis. Mohammad Alizadeh, AH., Abbasinazari, M., Hatami, B., et al.[2022]

The prodrug 1-(2,6-dichlorophenyl)indolin-2-one shows significant anti-inflammatory effects similar to diclofenac but without causing gastric ulceration, making it a safer long-term NSAID option.

This prodrug effectively reduces levels of PGE(2), COX-2 expression, and cellular influx in inflammation models, indicating its potential for treating inflammatory conditions without the common side effects associated with traditional NSAIDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological evaluation and preliminary pharmacokinetics studies of a new diclofenac prodrug without gastric ulceration effect. Santos, JL., Moreira, V., Campos, ML., et al.[2021]

In a study involving rats, rebamipide effectively prevented gastric hemorrhage caused by indometacin and stress, outperforming other control drugs like teprenone and cimetidine.

The results suggest that reactive oxygen species from neutrophils contribute to gastric hemorrhage during acute gastritis, indicating a potential mechanism for rebamipide's protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of rebamipide on indometacin-induced gastric hemorrhage in rats under restraint stress. Yamasaki, K., Arakawa, T., Takaishi, O., et al.[2016]

In a rat model, rebamipide effectively protected against small intestinal mucosal injury caused by indomethacin, reducing harmful bacteria levels and restoring them to normal.

Rebamipide also decreased the expression of inflammatory genes like TNFα, suggesting it could be a preventive treatment for gastrointestinal injuries caused by non-steroidal anti-inflammatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model. Kurata, S., Nakashima, T., Osaki, T., et al.[2020]

Rectal indomethacin significantly reduces the incidence of post-ERCP pancreatitis (PEP) in high-risk patients, with a relative risk of 0.43, based on a meta-analysis of 8 trials involving 3778 participants.

In contrast, rectal indomethacin does not show a significant protective effect against PEP in average-risk patients, indicating that its benefits are primarily limited to those at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectal indomethacin is protective against post-ERCP pancreatitis in high-risk patients but not average-risk patients: a systematic review and meta-analysis. Inamdar, S., Han, D., Passi, M., et al.[2022]

Etoricoxib 120 mg once daily is as effective as traditional NSAIDs like indometacin and diclofenac in providing pain relief and reducing inflammation in acute gout, based on a review of six trials with 851 patients.

Etoricoxib has a lower incidence of adverse events compared to NSAIDs, making it a safer option for patients suffering from acute gout.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of etoricoxib compared with NSAIDs in acute gout: a systematic review and a meta-analysis. Zhang, S., Zhang, Y., Liu, P., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10576534/

Rectal Indomethacin Dose Escalation (RIDE) for Prevention of ... Although rectal indomethacin (100mg) is effective in reducing the frequency and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05572788

Rectal Indomethacin to Prevent Acute Pancreatitis in EUS- ... The aim of this randomized trial is to compare the rate of post-procedure pancreatitis in patients undergoing EUS-FNA of pancreatic cysts; patients will receive ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1111103

A Randomized Trial of Rectal Indomethacin to Prevent Post ... Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17355281/

Indomethacin may reduce the incidence and severity of ... Conclusions: This trial shows that rectal indomethacin given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis.

5. withpower.com withpower.com/trial/phase-cysts-8-2022-f8cfa

Indomethacin for Preventing Acute Pancreatitis After EUS- ... Research shows that Indomethacin is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01912716

Rectal Indomethacin in the Prevention of Post-ERCP ... The purpose of this study is to determine whether a dose of 200 mg, administered as rectal suppositories, is more effective than the standard dose of 100 mg.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38219767/

Indomethacin with or without prophylactic pancreatic stent ... Interpretation: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy ...