Post-ERCP Pancreatitis, Pancreatitis
Conditions
Keywords
ERCP, Post-ERCP pancreatitis, Aggressive hydration, Lactated Ringer's solution, Rectal indomethacin, Fluid resuscitation, Same-day discharge
Brief summary
Post-ERCP pancreatitis (PEP) is the most common serious adverse event after endoscopic retrograde cholangiopancreatography (ERCP), occurring in roughly 7-15% of patients. Rectal non-steroidal anti-inflammatory drugs (NSAIDs) and peri-procedural aggressive intravenous hydration each reduce PEP, but published hydration regimens are delivered over 8-24 hours and require an overnight hospital stay, which is impractical where ERCP is increasingly performed as a same-day procedure. This multicentre, prospective, randomised controlled trial tests whether a short (under 4 hours) aggressive hydration regimen with Lactated Ringer's solution, combined with rectal indomethacin, is superior to standard care (rectal indomethacin plus low-volume hydration) for preventing PEP, while supporting same-day discharge. Adults undergoing ERCP are randomised 1:1. The primary outcome is the incidence of PEP defined by consensus (Cotton) criteria. A total of 1300 participants (650 per arm) will be enrolled.
Detailed description
Design: multicentre, parallel-group, superiority RCT with 1:1 allocation, conducted in high-volume tertiary academic endoscopy units. Interventions: All participants receive 100 mg indomethacin per rectum within 30 minutes before or after ERCP. Participants randomised to aggressive hydration receive a peri-procedural bolus of Lactated Ringer's 20 mL/kg over \ 1 hour, then 3 mL/kg/hour for 3 hours (post-procedure infusion capped at 1000 mL). Participants randomised to standard care receive low-volume Lactated Ringer's at the discretion of the endoscopist/anaesthetist (up to 1.5 mL/kg/hour, max 500 mL over 3 hours). For BMI \> 40 kg/m2, infusion rates are capped assuming a BMI of 40. Pancreatic duct stenting is permitted in both arms at the proceduralist's discretion per guidelines. Aggressive hydration is discontinued if signs of fluid overload develop. Follow-up: pre-discharge assessment (fluid-overload exam, pain), a 24-hour telephone follow-up (bloods if symptomatic), and a 30-day telephone follow-up for delayed events and hospitalisation. Analysis: primary analysis by intention-to-treat; per-protocol analysis also performed. Statistical analysis is conducted blinded to allocation.
Interventions
OTHERShort-Stay Aggressive Hydration
Lactated Ringer's bolus 20 mL/kg over \~1 hour then 3 mL/kg/hour x 3 hours (cap 1000 mL post-procedure); rate capped at BMI 40 if BMI \> 40.
OTHERStandard Peri-procedural Hydration
Low-volume Lactated Ringer's at operator discretion, up to 1.5 mL/kg/hour, max 500 mL over 3 hours.
Indomethacin 100 mg per rectum within 30 minutes before, during or after ERCP.
Sponsors
Westmead Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age over 18 years * Undergoing ERCP * Able to provide informed consent
Exclusion criteria
* Unable to give consent * Clinical signs/symptoms of congestive cardiac failure (pitting oedema, NYHA class ≥ 2, or oxygen saturation ≤ 90%) * Respiratory failure (pre-procedure SpO2 \< 90% on room air, or requirement for non-invasive/mechanical ventilation) * Contraindication to rectal NSAIDs (allergy; active gastrointestinal bleeding) * Estimated GFR (MDRD) ≤ 30 mL/min * Altered biliary or duodenal anatomy (e.g. prior biliary/pancreatic surgery, Roux-en-Y reconstruction) * Known hypo- or hypernatraemia (serum sodium \< 130 or \> 150 mmol/L) * Pregnancy * Severe liver disease (cirrhosis with ascites) * Previous sphincterotomy (unless undergoing pancreatic duct intervention) * Acute pancreatitis * Chronic pancreatitis (unless undergoing a pancreatic duct intervention) * Sphincter of Oddi dysfunction * Pancreatic mass causing biliary obstruction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of post-ERCP pancreatitis (PEP) | Within 72 hours after ERCP (onset within 24 hours) | PEP defined by consensus (Cotton) criteria, requiring ALL of: new or worsened upper abdominal pain; serum amylase or lipase at least 3x the upper limit of normal; pain and enzyme elevation persisting for at least 24 hours; and hospitalisation (or prolongation) of at least 2 days attributable to pancreatitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PEP not fulfilling full Cotton criteria | Within 72 hours after ERCP (onset within 24 hours) | Post-ERCP pancreatitis not meeting full Cotton criteria. |
| Delayed PEP | 24 hours to 30 days after ERCP | Post-ERCP pancreatitis (by Cotton criteria) with onset more than 24 hours after ERCP, identified after initial discharge. |
| Severity of PEP | Within 30 days after ERCP | Severity graded by Cotton criteria and the Revised Atlanta Classification |
| ERCP associated adverse events | Within 30 days after ERCP | ERCP-associated adverse events graded by consensus (Cotton) criteria as mild, moderate, or severe: bleeding, perforation, and infection (cholangitis). |
| Signs of fluid overload | Peri-procedural to 24 hours after ERCP | Pulmonary oedema, peripheral (pitting) oedema, or exacerbation of congestive cardiac failure. |
| Hospitalization for any reason within 30 days | Within 30 days after ERCP | Proportion of participants hospitalised (including unplanned admission or readmission) for any reason within 30 days of ERCP. Ascertained from medical records and the 30-day follow-up call. |
| Cost effectiveness | Within 30 days after ERCP | Cost-effectiveness of short-stay aggressive hydration versus standard care, comparing total cost of healthcare resource use (intravenous fluids and consumables, procedure/recovery time, length of stay, and PEP-related admissions or readmissions) in relation to PEP cases avoided. Reported as incremental cost effectiveness ratio (ICER) for post-ERCP pancreatitis cases avoided. |
| Hospitalization Length of Stay | Within 30 days of ERCP | In participants hospitalised (including unplanned admission or readmission) for any reason within 30 days of ERCP, the length of hospital stay measured in days. Ascertained from medical records and the 30-day follow-up call. |
| Hospitalization for PEP Length of Stay | Within 30 days of ERCP | In participants hospitalised (including unplanned admission or readmission) for PEP within 30 days of ERCP, the length of hospital stay measured in days. Ascertained from medical records and the 30-day follow-up call. |
Countries
Australia
Contacts
CONTACTNicholas Burgess
CONTACTBrian Lam
PRINCIPAL_INVESTIGATORNicholas Burgess
Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, Australia
Outcome results
None listed