Review for 10.1186/s12876-022-02462-z (2022)

Reviewer’s report
Title: 
Effect of ice water injection toward the duodenal papilla for preventing
post-ERCP pancreatitis: study protocol for 
a multicenter, single-blinded,
randomized controlled trial (EUTOPIA study)
Version: 
0 
Date: 
05 Jul 2022
Reviewer's report:
Dear Editorial team, 
In this manuscript titled, 'Effect of ice water injection toward the duodenal
papilla for preventing post-ERCP pancreatitis: study protocol for a multicenter,
single-blinded, randomized controlled trial (EUTOPIA study),' the authors
Azuma S et al., report the protocol of a randomized controlled trial evaluating
the role of using ice water in reducing the risk of post-ERCP pancreatitis. The
authors plan to flush the papilla with 250 ml of ice water towards the end of
ERCP in 440 cases, and a similar number of controls; with the goal of reducing
edema and inflammation in the papilla. The idea is simple and mechanistically
interesting, with a potential in contributing to further reducing the risk of
pancreatitis with an inexpensive, potentially safe intervention. 
The authors should be commended for their efforts and below are some
comments, hoping to further strengthen the study. 
Major comments:
1. Given that patients at high risk of pancreatitis are also being included, what
other prophylaxis is allowed - pancreatic duct stent, NSAIDs, IV fluids etc. If
these prophylaxes are allowed, how will the study results be adjusted to the
effect of these prophylaxes.
2. Are there plans for interim analyses, stopping rules of efficacy or futility 
Minor comments:
1. Given this is a clinical trial setting, will the temperature of the ice water be
measured, maintained, for uniformity.
2. Will patients with pancreas divisum, minor papilla interventions be excluded? 
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