Clinical trial NCT05381428: Prophylaxis of Post-ERCP Acute Pancreatitis
Official title: Prophylaxis of Post-ERCP Acute Pancreatitis: a Randomized, Multicenter, Open-label Study Comparing Indomethacin Versus Indomethacin-ringer Lactate Combination
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pancreatitis, Acute
Lead sponsor: Azienda USL Reggio Emilia - IRCCS
Sponsor class: OTHER_GOV
First posted: 2022-05-19
Enrollment: 1250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Incidence of PEP
timeFrame: Assessed 24 hours after procedure
Secondary outcomes:
measure: Severity of PEP
timeFrame: Assessed 72 hours after the onset of acute pancreatitis
measure: Increased amylase and lipase
timeFrame: Assessed 24 hours from baseline
measure: Onset of any adverse events
timeFrame: 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;
measure: Duration of Hospitalisation
timeFrame: Assessed average length of stay up to 30 days
Other outcomes:
Locations:
city: Baggiovara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena - Ospedale civile di Baggiovara
state: Modena
city: Carpi
country: Italy
facility: Azienda USL di Modena - Ospedale di Carpi
state: Modena
city: Fidenza
country: Italy
facility: Ospedale di Fidenza - AUSL di Parma
state: Parma
city: Bologna
country: Italy
facility: AUSL Bologna - Ospedale Maggiore Carlo Alberto Pizzardi
city: Bologna
country: Italy
facility: IRCSS - Policlinico S.Orsola-Malpighi
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale sant'Anna
city: Forlì
country: Italy
facility: AUSL della Romagna - Ospedale Morgagni-Pierantoni di Forlì
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena - Policlinico di Modena
city: Parma
country: Italy
facility: Azienda Ospedaliero - Universitaria di Parma
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto - AUSL Piacenza
city: Ravenna
country: Italy
facility: AUSL Romagna - Ospedale Santa Maria delle Croci
city: Reggio Emilia
country: Italy
facility: AUSL- IRCCS di Reggio Emilia
city: Rimini
country: Italy
facility: AUSL della Romagna - Ospedale Infermi di Rimini
Study officials:
affiliation: AUSL-IRCCS di Reggio Emilia
name: Vincenzo Giorgio Mirante
role: PRINCIPAL_INVESTIGATOR
References: