ERCP, Pancreatitis, Non-steroidal Anti-inflammatory (NSAID), Indomethacin, Diclofenac
Conditions
Brief summary
Pancreatitis is the most common and serious complication following post-endoscopic retrograde cholangiopancreatography (ERCP) and is associated with occasional mortality, extended hospital stays, and increased healthcare expenses. Preprocedural administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) was demonstrated to be an effective and convenient strategy for post-ERCP pancreatitis (PEP). Furthermore, several meta-analyses found that only 100mg indomethacin and diclofenac could effectively reduce PEP. Therefore, updated international clinical practice guidelines uniformly recommended administration of 100mg indomethacin or diclofenac in patients without contradictions. However, it was unclear which one of the two drug is more superior. A recent meta-analysis suggested 100mg rectal diclofenac was more efficacious than same-dose rectal indomethacin in PEP prevention (relative risk (RR) 0·59, 95% confidence intervals (CI) 0·40-0·89). Based on the results, we conducted a multicenter, double-blind, control trial to investigate whether 100mg diclofenac is superior than same-dose indomethacin. This trial planned to enroll 3612 patients in total. However, in the first interim analysis, PEP occurred in 53 patients (8.8%) of 600 patients allocated to diclofenac group and 37 patients (6.1%) of 604 patients allocated to indomethacin group (relative risk (RR) 1.44; 95% confidence interval (CI) 0.96-2.16, p=0.074). Thus, the trial was stopped according to the futility rule of conditional power. However, it was worth noticing that PEP tended to be higher in diclofenac group than that in indomethacin group. A sample size of 1204 was under power to draw the conclusion of significantly lower PEP rate in indomethacin group and thus a new trial with larger sample size of sufficient power is predicted to prove the superiority of indomethacin over diclofenac. Here we conducted a multicenter, randomized, double-blind trial to investigate whether 100mg indomethacin is superior to 100mg diclofenac in preventing PEP.
Interventions
All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure
DRUGDiclofenac 100mg
All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure
Sponsors
Air Force Military Medical University, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* 18-90 years old patients with native papilla who planned to undergo ERCP
Exclusion criteria
* Previous biliary sphincterotomy and papillary large balloon dilation * Planned for placements of pancreatic duct stents (eg. pancreatic duct strictures, planned ampullectomy) * Allergy to NSAIDs * The administration of NSAIDs within 7 days * Not suitable for NSAIDs administration (gastrointestinal hemorrhage within 4 weeks, renal dysfunction \[Cr \>1.4mg/dl=120umol/l\]; presence of coagulopathy before the procedure) * Acute pancreatitis within 7 days before ERCP or acute pancreatitis with obvious Pancreatic edema and peripancreatic fluid collections * Hemodynamical instability * Pregnancy or lactation * Unable to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of post-ERCP Pancreatitis | 30 days | a new or aggravated upper abdominal pain, with an elevated pancreatic enzyme of at least 3 times as the upper limit of normal value 24h after procedure and prolonged hospitalization days for at least 2 days. This definition was based on a widely recognized Cotton consensus |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria | 30 days | Mild: The most common form of acute pancreatitis, without organ failure or local or systemic complications, generally resolving within 1 week of onset. Moderately Severe: the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe: persistent organ failure, that is, organ failure \>48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). |
| Rate of ERCP-related perforation | 30 days | Perforation was established according to Cotton criteria, Mild: slight leakage of fluid or contrast dye, manageable through fluid administration and suction therapy ≤3 days Moderate: definite perforation required to be managed for 4-10 days Severe: management for more than 10 days or requiring for percutaneous or surgical intervention. |
| Rate of ERCP-related infection | 30 days | Infection was established according to Cotton criteria. Mild: temperature \>38℃ for 24-48h Moderate: Febrile illness requiring \>3 days of hospital treatment; endoscopic or percutaneous interventions; Severe: septic shock or requiring surgery. |
| Rate of mild, moderate or severe PEP | 30 days | The severity classification of post-ERCP pancreatitis was defined according to the Cotton Criteria. Mild PEP: with an extension of hospitalization period of 2-3 days; Moderate PEP: with an extension of hospitalization period of 4-10 days; Severe PEP: with an extension of more than 10 days, or hemorrhagic pancreatitis, phlegmon, or pseudocyst, intervention (percutaneous drainage or surgery), or death. |
| Rate of NSAIDs-related complications | 30 days | NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death |
| Rate of mortality | 30 days | — |
| The rate of total adverse events | 30 days | Adverse events include ERCP-related or non ERCP-related adverse events |
| Rate of ERCP-related bleeding | 30 days | Bleeding was established according to Cotton criteria. Mild: a documented decrease in hemoglobin concentration by \<3 g/L, without requiring the blood transfusion; Moderate: blood transfusion ≤4 units; without need for angiographic or surgery interventions Severe: Transfusion: ≥5 units or requiring for angiographic or surgery interventions. |
Countries
China
Contacts
Primary ContactYanglin Pan, MD
Outcome results
None listed