Tacrolimus as Prophylaxis of Post-ERCP Pancreatitis

Tacrolimus as Prophylaxis of Post-ERCP Pancreatitis: a DPSG (Dutch Pancreatitis Study Group) Multicenter, Double-blind, Randomized, Placebo-controlled Study.

The goal of this clinical trial is to learn if a single intravenous dose of tacrolimus, given before an ERCP procedure (an endoscopic procedure of the bile ducts and pancreas), can prevent post-ERCP pancreatitis (PEP) in adults at moderate-to-high risk of developing this complication.

The main question it aims to answer is:

• Does a single dose of tacrolimus lower the number of participants who develop pancreatitis after ERCP?

Researchers will compare tacrolimus to a placebo (a look-alike solution with no active drug) to see if tacrolimus reduces the occurrence of PEP.

Participants will:

• Receive an intravenous infusion of either tacrolimus or placebo, given over 60 minutes, ending before the start of the ERCP procedure
• Receive standard preventive treatment (a rectal anti-inflammatory medication (NSAID)) in addition to the study infusion
• Be contacted by phone 48 hours after the procedure to check for symptoms
• Complete questionnaires about quality of life and healthcare use, and be followed for 12 weeks after the procedure
• The first 40 enrolled patients will have extra blood samples taken to measure tacrolimus levels.

Inclusion Criteria:

• Age 18 years or older
• Indication for ERCP
• Ability to provide written informed consent

Exclusion Criteria:

• Previous sphincterotomy or sphincteroplasty
• Routine biliary stent exchange
• Altered anatomy or biliodigestive anastomosis
• Chronic pancreatitis according to the M-ANNHEIM criteria
• Active pancreatitis
• Sepsis or ASA IV
• Contraindication for tacrolimus or diclofenac (allergy, potassium >5 mmol/L, eGFR <30 mL/min)
• Pregnancy or breastfeeding
• Current tacrolimus or ciclosporin use
• Current use of medications contraindicated with tacrolimus, including strong CYP3A4/3A5 inhibitors (e.g., ketoconazole, voriconazole, posaconazole, itraconazole, clarithromycin, josamycin, ritonavir, cobicistat) or CYP3A4/3A5 inducers (e.g., rifampicin, carbamazepine, phenytoin, St. John's wort)