Prophylaxis of Post-ERCP Acute Pancreatitis

NCT ID: NCT05381428

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-13
• Study Completion Date: 2024-10-12

Brief Summary

This study aims to compare indomethacin and the combination of indomethacin and aggressive lactated Ringer infusion in terms of efficacy in preventing post-ERCP acute pancreatitis (PEP).

Detailed Description

This study aims to compare indomethacin and the combination of indomethacin and aggressive lactated Ringer infusion in terms of their efficacy in preventing PEP regardless of baseline risk in all eligible patients who have consecutively undergone ERCP. The intention is to confirm initial literature finding with a large sample size and a prospective, randomised, multicentre design to study and compare the efficacy of the two different prophylaxis strategies. The interest is determined by the need to assess whether there is a superiority of combination prophylaxis with indomethacin and a strong infusion of lactated Ringer against the exclusive administration of endorectal indomethacin, with a consequent considerable impact on the management of PEP. Shouldn't forget that both indomethacin and lactated Ringer have in the various studies only reduced the incidence of PEP compared to placebo. Therefore, PEP remains a possible complication even after prophylaxis with a single measure, even in low-risk patients. If the study demonstrates the superiority of combination prophylaxis, it could offer this to all patients with gains in PEP, hospitalisation, and complication management costs.

It should be noted that, compared with previous studies, this protocol doesn't include a placebo control arm. This choice, shared by all the centres involved, is dictated by the awareness that literature studies have already documented the superiority of both indomethacin and Ringer's lactate in PEP prophylaxis compared to placebo. Moreover, although some studies raise doubts about the prophylactic efficacy of indomethacin in low-risk patients, it was decided not to include a placebo arm because of ethical misgivings about not proposing a treatment with a low risk of side events, as recommended moreover by international guidelines.

Finally, the study aims to assess the occurrence of any adverse events in the two groups studied.

Conditions

Pancreatitis, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Indomethacin Group (Control Arm)

Patients will be randomized to receive a 100 mg indomethacin suppository will be administered immediately before the endoscopic procedure (20-30 minutes) and saline infusion will be given as needed.

Group Type: ACTIVE_COMPARATOR

Indomethacin suppository

Intervention Type: DRUG

Control Group: Patients will be randomized to receive a 100 mg indomethacin suppository will be administered immediately before the endoscopic procedure (20-30 minutes) and saline infusion will be given as needed.

Indomethacin and Lactated Ringer Group (Intervention Arm)

Patients will be randomized to receive an indomethacin suppository that will be administered immediately before (20-30 minutes) the endoscopic procedure in combination with a lactated Ringer's infusion that will be administered with the following weight-based schedule: 3 cc/kg/h during ERCP, a bolus of 20 cc/kg after ERCP, and again 3 cc/kg/h for 8 hours after ERCP.

Group Type: EXPERIMENTAL

Indomethacin suppository and high-flow lactated ringer infusion combination

Intervention Type: COMBINATION_PRODUCT

Interventional group: Patients will be randomized to receive an indomethacin suppository that will be administered immediately before (20-30 minutes) the endoscopic procedure in combination with a lactated Ringer's infusion that will be administered with the following weight-based schedule: 3 cc/kg/h during ERCP, a bolus of 20 cc/kg after ERCP, and again 3 cc/kg/h for 8 hours after ERCP.

Interventions

Indomethacin suppository

Control Group: Patients will be randomized to receive a 100 mg indomethacin suppository will be administered immediately before the endoscopic procedure (20-30 minutes) and saline infusion will be given as needed.

Intervention Type: DRUG

Indomethacin suppository and high-flow lactated ringer infusion combination

Interventional group: Patients will be randomized to receive an indomethacin suppository that will be administered immediately before (20-30 minutes) the endoscopic procedure in combination with a lactated Ringer's infusion that will be administered with the following weight-based schedule: 3 cc/kg/h during ERCP, a bolus of 20 cc/kg after ERCP, and again 3 cc/kg/h for 8 hours after ERCP.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• Age > 18 years;
• All naïve patients consecutively undergoing ERCP and with any indication;
• Obtaining informed consent.

Exclusion Criteria

• Refusal or inability to sign informed consent;
• Patients undergoing ERCP for diagnostic purposes only;
• Patients with ongoing acute pancreatitis;
• Patients with known allergy/hypersensitivity to NSAIDs;
• Patients with hypersensitivity to the active ingredients or any of the excipients of Ringer
• Lactate;
• Patients with a personal or family history of Stevens-Johnson or Lyell syndrome;
• Patients already receiving treatment with NSAIDs within 7 days prior to ERCP;
• Patients with recent gastrointestinal bleeding (less than 30 days after ERCP), or with history of recurrent bleeding/ulcer peptic ulcer or bleeding/perforation after previous NSAID treatment;
• Patients who are candidates for or have previously undergone endoscopic papillectomy;
• Patients with a positive history of recent myocardial infarction (less than 6 months after the procedure), heart failure, severe myocardial insufficiency (NYHA class > II), respiratory failure with chronic need for oxygen therapy, known pulmonary hypertension;
• Patients with ventricular fibrillation;
• Patients with ongoing therapy with cardioactive glycosides;
• Patients with chronic renal failure (creatinine clearance values less than 40 ml/min);
• Cirrhotic patients in Child B and C class;
• Patients with severe hydro-electrolyte imbalances (hypernatremia > 150 mEq/L, hyponatremia < 130 mEq/L; hypercalcemia, hyperKalemia);
• Metabolic and respiratory alkalosis;
• Patients with epilepsy or Parkinson's disease;
• Patients with psychiatric disorders;
• Patients with a history of major surgery of the upper digestive tract (Billroth II, Roux-en-Y anastomosis);
• Pregnancy or lactation;
• Sarcoidosis;
• Untreated Addison's disease;
• Active proctitis of any etiology.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda USL Reggio Emilia - IRCCS

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Romano Sassatelli

Role: PRINCIPAL_INVESTIGATOR

AUSL-IRCCS di Reggio Emilia

Locations

Azienda Ospedaliero-Universitaria di Modena - Ospedale civile di Baggiovara

Baggiovara, Modena, Italy

Azienda USL di Modena - Ospedale di Carpi

Carpi, Modena, Italy

AUSL Bologna - Ospedale Maggiore Carlo Alberto Pizzardi

Bologna, , Italy

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale sant'Anna

Ferrara, , Italy

AUSL della Romagna - Ospedale Morgagni-Pierantoni di Forlì

Forlì, , Italy

Azienda Ospedaliero - Universitaria di Parma

Parma, , Italy

Ospedale Guglielmo da Saliceto - AUSL Piacenza

Piacenza, , Italy

AUSL Romagna - Ospedale Santa Maria delle Croci

Ravenna, , Italy

AUSL- IRCCS di Reggio Emilia

Reggio Emilia, , Italy

AUSL della Romagna - Ospedale Infermi di Rimini

Rimini, , Italy

Countries

Italy

Other Identifiers

RCT-PRO-PEP-INDO-RING

Identifier Type: -

Identifier Source: org_study_id