Prophylaxis of Post-ERCP Acute Pancreatitis

Pancreatitis, Acute Clinical Trial

— PEPPER  

Official title:

Prophylaxis of Post-ERCP Acute Pancreatitis: a Randomized, Multicenter, Open-label Study Comparing Indomethacin Versus Indomethacin-ringer Lactate Combination

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05381428
• Other study ID #: RCT-PRO-PEP-INDO-RING
• Status: Recruiting
• Phase: Phase 3
• Start date: May 13, 2022
• Est. completion date: February 2025

Study information

• Verified date: May 2022
• Source: Azienda Unità Sanitaria Locale Reggio Emilia
• Contact: Vincenzo Giorgio Mirante, MD
• Phone: +390522242910
• Email: vincenzogiorgio.mirante[@]ausl.re.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1250
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatitis
• Pancreatitis, Acute

Intervention

Drug:
• 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.

Combination Product:
• 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.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria di Modena - Ospedale civile di Baggiovara	Baggiovara	Modena
Italy	AUSL Bologna - Ospedale Maggiore Carlo Alberto Pizzardi	Bologna
Italy	IRCSS - Policlinico S.Orsola-Malpighi	Bologna
Italy	Azienda USL di Modena - Ospedale di Carpi	Carpi	Modena
Italy	Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale sant'Anna	Ferrara
Italy	Ospedale di Fidenza - AUSL di Parma	Fidenza	Parma
Italy	AUSL della Romagna - Ospedale Morgagni-Pierantoni di Forlì	Forlì
Italy	Azienda Ospedaliero-Universitaria di Modena - Policlinico di Modena	Modena
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

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Unità Sanitaria Locale Reggio Emilia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of PEP	Onset of acute post-ERCP pancreatitis (PEP) at 24 hours after the procedure according to Cotton's criteria [Mild, Moderate, Severe]	Assessed 24 hours after procedure
Secondary	Severity of PEP	The effect on the severity of pancreatitis occurring in patients treated with indomethacin or indomethacin and lactated Ringer's will be evaluated and compared according to Atlanta's criteria [Mild, Moderate, Severe] (72 hours after the onset of acute pancreatitis).	Assessed 72 hours after the onset of acute pancreatitis
Secondary	Increased amylase and lipase	The effect on the occurrence of increased amylase and lipase values in patients treated with indomethacin or indomethacin and Ringer's lactate will be evaluated and compared.; The difference in plasma amylase and lipase levels post-ERCP will be assessed at 24 hours from baseline.	Assessed 24 hours from baseline
Secondary	Onset of any adverse events	The onset of any adverse event will be evaluated and compared, specifically: intra-operative bleeding; Postoperative bleeding (within 30 days of the procedure); increased plasma creatinine compared to baseline (at 24 hours post-procedure); pulmonary edema (2, 8 and 24 hours after the procedure); fluid overload (2, 8 and 24 hours after the procedure); other (events that happened during the hospital stay and related to the procedure or study).	Assessed postoperative bleeding within 30 days of surgery; increased plasma creatinine at 24 hours post-procedure; pulmonary oedema at 2, 8 and 24 hours after the procedure; water overload at 2, 8 and 24 hours after the procedure;
Secondary	Duration of Hospitalisation	The average duration of hospitalization in the two arms will be evaluated up to 30 days after randomization.	Assessed average length of stay up to 30 days