Indomethacin vs Diclofenac for Preventing PEP
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-90
SponsorAir Force Military Medical University, China
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
18-90 years old patients with native papilla who planned to undergo ERCP
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Indomethacin 100 MG
DrugAll patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure
Diclofenac 100mg
DrugAll patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure
Treatment groups
4,050 Participants
are divided into 2 treatment groupsGroup A: IndomethacinExperimental treatment 1 intervention
Group B: Diclofenac groupActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Rate of post-ERCP Pancreatitis
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
Time frame
30 daysSecondary outcomes
1
Rate of mild, moderate or severe PEP
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.
Time frame
30 days2
Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria
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).
Time frame
30 days3
Rate of ERCP-related perforation
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.
Time frame
30 days4
Rate of ERCP-related infection
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.
Time frame
30 daysSponsors and contacts
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Source ClinicalTrials.gov