Pancreatitis, AcutePhase 3PEPPERNCT05381428
Prophylaxis of Post-ERCP Acute Pancreatitis
A Phase 3 study testing Indomethacin suppository and Indomethacin suppository and high-flow lactated ringer infusion combination in people with Pancreatitis, Acute, run by Azienda USL Reggio Emilia - IRCCS at 10 sites in Italy.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatitis, Acute
- What is being tested?
- Indomethacin suppository and Indomethacin suppository and high-flow lactated ringer infusion combination
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 10 sitesItaly
- Study dates
- 13 May 2022to 12 Oct 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years;
- All naïve patients consecutively undergoing ERCP and with any indication;
- Obtaining informed consent.
Who cannot join
- 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;
Show all 24Show fewer
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Italy10 sites
Azienda Ospedaliero-Universitaria di Modena - Ospedale civile di Baggiovara
Baggiovara, Modena, 41126
AUSL Bologna - Ospedale Maggiore Carlo Alberto Pizzardi
Bologna, 40133
Azienda USL di Modena - Ospedale di Carpi
Carpi, Modena, 41121
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale sant'Anna
Ferrara, 44124
AUSL della Romagna - Ospedale Morgagni-Pierantoni di Forlì
Forlì, 47121
Azienda Ospedaliero - Universitaria di Parma
Parma, 43100
Ospedale Guglielmo da Saliceto - AUSL Piacenza
Piacenza, 29121
AUSL Romagna - Ospedale Santa Maria delle Croci
Ravenna, 48100
AUSL- IRCCS di Reggio Emilia
Reggio Emilia, 42122
AUSL della Romagna - Ospedale Infermi di Rimini
Rimini, 47920
About this study
Official title: Prophylaxis of Post-ERCP Acute Pancreatitis: a Randomized, Multicenter, Open-label Study Comparing Indomethacin Versus Indomethacin-ringer Lactate Combination
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).
Read the 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
- Being tested
- Indomethacin suppository, Indomethacin suppository and high-flow lactated ringer infusion combination
- Medical subject headings
- Pancreatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indomethacin suppositoryDrug
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 suppository and high-flow lactated ringer infusion combinationCombination 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.
| Study group | Role | What they receive |
|---|---|---|
| Indomethacin Group (Control Arm) | Active comparator | 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. Receives: Drug: Indomethacin suppository |
| Indomethacin and Lactated Ringer Group (Intervention Arm) | Experimental | 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. Receives: Combination Product: Indomethacin suppository and high-flow lactated ringer infusion combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of PEP
Onset of acute post-ERCP pancreatitis (PEP) at 24 hours after the procedure according to Cotton's criteria [Mild, Moderate, Severe]
Measured: Assessed 24 hours after procedure
Secondary outcomes (4)
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).
Measured: Assessed 72 hours after the onset of acute pancreatitis
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.
Measured: Assessed 24 hours from baseline
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).
Measured: 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;
Duration of Hospitalisation
The average duration of hospitalization in the two arms will be evaluated up to 30 days after randomization.
Measured: Assessed average length of stay up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2022
- Study start13 May 2022
- Primary completion12 Oct 2024
- Study completion12 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatitis, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda USL Reggio Emilia - IRCCS
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Romano Sassatelli, Principal investigator, AUSL-IRCCS di Reggio Emilia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05381428
- Sponsor's protocol ID
- RCT-PRO-PEP-INDO-RING
- Acronym
- PEPPER
- Status last verified
- Jun 2025
- First submitted
- 9 May 2022
- Last updated
- 24 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylaxis of Post-ERCP Acute Pancreatitis: a Randomized, Multicenter, Open-label Study Comparing Indomethacin Versus Indomethacin-ringer Lactate Combination
- ClinicalTrials.gov ID
- NCT05381428
- Acronym / sponsor ID
- PEPPER / RCT-PRO-PEP-INDO-RING
- Conditions
- Pancreatitis, Acute
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- Azienda USL Reggio Emilia - IRCCSOther government
- Study start
- 13 May 2022 (actual)
- Primary completion
- 12 Oct 2024 (actual)
- Study completion
- 12 Oct 2024 (actual)
- First posted
- 19 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Indomethacin Group (Control Arm) | Active comparator | Drug: Indomethacin suppositoryPatients 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) | Experimental | Combination Product: Indomethacin suppository and high-flow lactated ringer infusion combinationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > 18 years;
- All naïve patients consecutively undergoing ERCP and with any indication;
- Obtaining informed consent.
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Indomethacin suppositoryControl 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. | Drug | Indomethacin Group (Control Arm) |
| Indomethacin suppository and high-flow lactated ringer infusion combinationInterventional 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. | Combination product | Indomethacin and Lactated Ringer Group (Intervention Arm) |
Primary outcome
Incidence of PEP
Time frame: Assessed 24 hours after procedure
Onset of acute post-ERCP pancreatitis (PEP) at 24 hours after the procedure according to Cotton's criteria [Mild, Moderate, Severe]
4 secondary outcomes
Severity of PEP
Time frame: Assessed 72 hours after the onset of acute pancreatitis
Increased amylase and lipase
Time frame: Assessed 24 hours from baseline
Onset of any adverse events
Time frame: 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;
Duration of Hospitalisation
Time frame: Assessed average length of stay up to 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Romano Sassatelli principal investigator
AUSL-IRCCS di Reggio Emilia
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Indomethacin suppository and Indomethacin suppository and high-flow lactated ringer infusion combination in people with Pancreatitis, Acute, run by Azienda USL Reggio Emilia - IRCCS at 10 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of PEP (time frame: Assessed 24 hours after procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2025; AzTrials last refreshed its copy on 6 Nov 2026.