Papillary Epinephrine Injection Combined With Rectal Indomethacin (PEIR-PEP)

Duzce University

Status and phase: Completed; Phase 4

Conditions: Post-ERCP Acute Pancreatitis

Treatments: Drug: Rectal indomethacin alone; Drug: Papillary epinephrine injection combined with rectal indomethacin

Study type: Interventional

Funder types: Other

Identifiers

NCT07173179

Rectal NSAID vs EI combo

Details and patient eligibility

About

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common and one of the most undesirable major adverse events after endoscopic retrograde cholangiopancreatography (ERCP), causing significant morbidity and even mortality. The incidence rate is almost 15% in high-risk patients and no less than 3% in average-risk patients.

Many factors contribute to PEP, such as patient-related and endoscopist-related factors, but mainly two mechanisms are considered in terms of physiopathology: papillary edema caused by mechanical trauma during cannulation and thermal injury with electrocautery current.

Rectal NSAIDs and pancreatic stent placement are the two proven methods of PEP prophylaxis that are included in the guideline recommendations, but despite the frequent use of these methods, the incidence rates are still more than acceptable. There is a need for additional methods that are easy to implement, preferably low cost, and safe to reduce the risk of PEP.

Topical epinephrine applied submucosally can be a method that meets these goals. Ampullary epinephrine injection is an effective method in terms of post sphincterotomy bleeding but to our knowledge, there is no study examining its efficacy in PEP prophylaxis except for one retrospective study that we reported.

There are conflicting reports on epinephrine spraying on the papilla in terms of PEP, but these trials are mostly heterogeneous with different dose regimens. It should also be noted that spraying epinephrine on the papilla has a length of action of about 1 to 5 minutes but the length of action for epinephrine injection is roughly 120 minutes.

Given this information, we designed a large-scale, double-blind, randomized, controlled, superiority trial.

Full description

Patient characteristics and procedure-related parameters will be recorded.

Patients will be divided into two as a patient group and a control group by 1:1 simple randomization. The patients in the indomethacin group will receive 100mg of rectal indomethacin alone, just before the procedure. In the combination group, the patients will receive 100mg of rectal indomethacin just before the procedure plus 4 quadrants of the peripapillary region will be injected with 1mL of undiluted epinephrine, 1 mL in each quadrant 1 to 2 cm away from the papillary orifice just before pulling out the duodenoscope.

The blood pressure, pulse rate, and electrocardiography will be monitored in all patients both during and after the procedure. All patients will be hospitalized for at least one night and the serum amylase and lipase levels will be measured before and again 4 hours after the procedures. Amylase, lipase, and other blood tests will also be performed routinely 24 hours after ERCP.

PEP was described as at least a threefold increase in amylase levels together with typical abdominal pain 24 hours after the procedure. Post-ERCP hyperamylasemia was defined using normal clinical conditions, but serum amylase levels were elevated above the normal upper limit (100 IU/L) 24 hours after the procedure. Patients at high risk for PEP and difficult cannulation were defined according to the European Society of Gastrointestinal Endoscopy Guidelines

Enrollment: 504 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients who submitted a written informed consent for this trial, and aged between 18-80 years old
• Patients who have naïve papilla (no previous procedure was performed at ampulla)
• Patients who is suspected to have a biliary obstruction or biliary disease
• Patients who are needed to have endoscopic retrograde cholangiopancreatography for treatment of biliary obstruction

Exclusion criteria

• Patients who are pregnant

• Patients with mental retardation

• Patients allergic to contrast agents

• Patients who received sphincterotomy or pancreatobiliary operation previously

• Patients who have ampulla of Vater cancer

• Patients who have difficulty with the approach to ampulla due to abdominal surgery including stomach cancer with Billroth II anastomosis

• Patients who have pancreatic diseases as below (at least one more);

  • acute pancreatitis within 30days before enrollment
  • idiopathic acute recurrent pancreatitis
  • pancreas divisum
  • obstructive chronic pancreatitis
  • pancreatic cancer

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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504 participants in 2 patient groups

Rectal indomethacin alone

Active Comparator group

Description:

All patients in this group receive preprocedural 100mg indomethacin spp

Treatment:

Drug: Rectal indomethacin alone

Rectal indomethacin combined wit papillary epinephrine injection

Experimental group

Description:

All patients in this group receive preprocedural 100mg indomethacin spp and post-procedure 4 ml of undiluted epinephrine injected around the duodenal papilla on four quadrants, over a period of 60 seconds using a sclerotherapy needle

Treatment:

Drug: Papillary epinephrine injection combined with rectal indomethacin