Indomethacin plus prophylactic pancreatic stent placement in patients with high-risk of pancreatitis after ERCP.

MEMBER ARTICLE

Elmunzer BJ, Foster LD, Serrano J, et al. Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial. Lancet. 2024 Jan...

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Elmunzer BJ, Foster LD, Serrano J, et al. Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial. Lancet. 2024 Jan 11:S0140-6736(23)02356-5.

Question/Hypothesis 

Could the use of indomethacin eliminate or substantially reduce the need for pancreatic stent placement in high-risk patients to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP)?

Design 

Randomized, non-inferiority trial conducted at 20 referral centers in the USA and Canada.

 

Patients

Patients (aged ≥18 years) at high risk for post-ERCP pancreatitis.

 

Interventions

Patients were randomly assigned in a 1:1 ratio to receive a prophylactic stent or not using an interactive web based central randomization system that implemented a minimal sufficient balance randomization scheme to control within-site treatment imbalance.

Outcome

The primary outcome measure was post-ERCP pancreatitis. Diagnosis was made according to validated consensus.

Data analysis

Indomethacin alone would become the dominant strategy in clinical practice if it resulted in no more than a 5% greater absolute risk of pancreatitis (non-inferiority margin) compared with the combination of indomethacin plus prophylactic stent.

Funding

A grant from US National Institutes of Health.

 

Results 

Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference, 3.6%; 95%CI 0.6-6.6; p=0.18 for non-inferiority). Because the upper bound of the 95% CI around the risk difference in post-ERCP pancreatitis between the groups exceeded 5%, noninferiority was not demonstrated. Since the CI around the risk difference excluded zero for the ITT population, a post-hoc one-sided test of the comparison of the two proportions indicated that indomethacin alone was inferior to indomethacin plus a prophylactic stent (p=0.011). The indomethacin alone group had a 32% higher risk of developing post-ERCP pancreatitis relative to the combination (relative risk 1.32; 95%CI 1.05-1.66).

COMMENTARY

Why Is This Important?

Preliminary studies have suggested that the administration of rectal NSAIDs might obviate the need for prophylactic stent placement. (1,2)

 

Key Study Findings

Indomethacin alone was not as effective as indomethacin plus prophylactic pancreatic stent placement. The relative benefit of stent placement appeared more prominent among those at the highest risk for post-ERCP pancreatitis.

 

Caution

This is a very nice paper challenging to carry out. I only have 2 concerns: first, in this study was a relatively large number of patients (n=514) with potential sphincter of Oddi disorder (SOD). After the EPISOD trial, many centers have steered away from ERCP in these patients (3,4). The inclusion of patients with presumptive SOD makes the conclusions more complicated to place into practice. Second, the predominant intravenous hydration used during the periprocedural period was lactated Ringer’s solution, which is known to be beneficial for post-ERCP pancreatitis prophylaxis. Aggressive hydration plus NSAID's exact role and utility remains an open issue.

 

My Practice

Regularly, I use PD stent in patients for whom I have an unintended PD cannulation. Regularly, I do not make efforts to place a PD stent, mainly because it might result in net harm because of the pancreatic trauma. Maybe with the current results, in patients with a high risk of post-ERCP pancreatitis, I must reconsider it.

 

REFERENCES 

• Elmunzer BJ, Higgins PD, Saini SD, et al. Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data. Am J Gastroenterol 2013; 108: 410–15.
• Akbar A, Abu Dayyeh BK, Baron TH, Wang Z, Altayar O, Murad MH. Rectal nonsteroidal anti-inflammatory drugs are superior to pancreatic duct stents in preventing pancreatitis after endoscopic retrograde cholangiopancreatography: a network meta-analysis. Clin Gastroenterol Hepatol 2013; 11: 778–83.
• Cotton PB, Durkalski V, Romagnuolo J, et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on painrelated disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA 2014; 311: 2101–09.
• Lopez-Cossio JA, Murcio-Pérez M, López Arce-Ángeles G, Borjas-Almaguer O, Téllez-Ávila FI. The efficacy and safety of endoscopic sphincterotomy in patients with Sphincter of Oddi dysfunction: a systematic review and meta-analysis. Surg Endosc. 2023 Dec;37(12):9062-9069.

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