Efficacy and Safety of a Novel Guidewire for Selective Biliary Cannulation: A Multicenter, Prospective Randomized Controlled Study

¹Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea

²Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

³Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

⁴Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea

Corresponding author : Se Woo Park Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 7 Keunjaebong-gil, Hwaseong 18450, Korea Tel. +82-31-8086-2858 E-mail: mdsewoopark@gmail.com

Corresponding author : Jae Hee Cho Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea Tel. +82-2-2019-3310 E-mail: jhcho9328@yuhs.ac

Received March 27, 2026 Revised May 11, 2026 Accepted May 15, 2026

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

요약

배경/목적

내시경역행담췌관조영술(endoscopic retrograde cholangiopancreatography)에서 가이드와이어 선택은 선택적 담관 삽관의 성공과 안전성에 중요하다. 본 다기관 무작위배정 비교임상시험은 새로 개발된 가이드와이어의 유효성과 안전성이 기존 가이드와이어에 비해 비열등함을 평가하고자 하였다.

방법

2024년 12월부터 2025년 7월까지 3개 상급종합병원에서 ERCP를 시행받은 환자 198명을 대상으로, 시험군과 대조군에 1:1로 무작위 배정하였다. 1차 평가변수는 선택적 담관 삽관 성공률이었으며, 2차 평가변수는 삽관 시간, 어려운 삽관 발생률, 시술 관련 이상반응이었다.

결과

총 198명(시험군 98명, 대조군 100명)이 분석에 포함되었고, 두 군의 기저 특성은 유사하였다. 선택적 담관 삽관 성공률은 시험군 99.0%, 대조군 96.0%로 사전에 설정한 비열등성 기준을 충족하였으며(군 간 차이 3.0%p, 95% 신뢰구간 -2.2에서 8.9), 시술후 췌장염 발생률은 두 군 간 유의한 차이가 없었다(5.1% vs. 4.0%, p=0.746). 반면, 어려운 삽관은 시험군에서 더 흔하게 발생하였다(29.6% vs. 15.0%, p=0.017).

결론

새로 개발된 가이드와이어는 선택적 담관 삽관 성공률과 이상반응 측면에서 기존 가이드와이어 대비 비열등함을 확인하였다.

Keywords: 내시경역행췌담관조영술, 유도철사, 담관, 도관 삽입

Abstract

Background/Aims

Guidewire selection is critical for endoscopic retrograde cholangiopancreatography (ERCP) in pancreatobiliary diseases. Our study evaluated the noninferiority of novel guidewire compared with conventional guidewire that is widely used in clinical practice.

Methods

A total of 198 patients with a native papilla undergoing ERCP at three tertiary hospitals were randomized in a 1:1 ratio to the test or control group. The primary endpoint was the selective biliary cannulation success rate. The secondary endpoints were the cannulation time, the incidence of difficult cannulation, and adverse events, including post-ERCP pancreatitis (PEP). Difficult cannulation was defined as a cannulation time of >5 minutes, more than five cannulation attempts, or at least one unintentional pancreatic duct cannulation.

Results

Among 198 patients analyzed (test: 98; control: 100), baseline characteristics were comparable. Selective biliary cannulation success was 99.0% in the test group and 96.0% in the control group; the between-group difference was 3.0 percentage points (95% CI, -2.2 to 8.9), with the lower CI bound above the prespecified -11% non-inferiority margin. PEP incidence was similar between groups (5.1% vs. 4.0%, p=0.746). However, difficult cannulation occurred more frequently in the test group than in the control group (29.6% vs. 15.0%; p=0.017), and the cannulation time was longer in the test group (5.7 vs. 3.4 minutes; p=0.011).

Conclusions

The novel guidewire met the prespecified non-inferiority criterion for selective biliary cannulation success compared with the conventional guidewire. Adverse event rates, including PEP, were similar between the groups. The novel guidewire was associated with a longer cannulation time.

Keywords: Cholangiopancreatography, endoscopic retrograde, Guidewires, Bile ducts, Catheterization

INTRODUCTION

Endoscopic retrograde cholangiopancreatography (ERCP) has traditionally played a pivotal role in the diagnosis and management of pancreatobiliary disorders. However, with advances in noninvasive cross-sectional imaging modalities, including computed tomography and magnetic resonance imaging, and given the invasive nature of ERCP and its associated risks—including post-ERCP pancreatitis (PEP), bleeding, and perforation—ERCP is now primarily reserved for therapeutic rather than diagnostic purposes. As a result, current ERCP practice emphasizes therapeutic intervention and ongoing refinement of techniques to improve ductal access and minimize complications [1,2].

Selective ductal cannulation is a prerequisite for therapeutic ERCP, and a variety of accessories and endoscopic techniques have been developed to facilitate biliary and pancreatic duct access. In routine practice, two principal approaches are commonly used for initial cannulation: contrast-assisted (contrast injection) cannulation and guidewire-assisted cannulation [3]. In the contrast-assisted approach, a cannula or sphincterotome is advanced into the papillary orifice, and contrast medium is injected to opacify and delineate the biliary tree. Conversely, the guidewire-assisted cannulation technique, introduced by Siegel in 1987, involves first advancing a guidewire into the target duct under fluoroscopic guidance, confirming appropriate wire position, and subsequently injecting contrast to define the ductal anatomy [3].

Accumulating evidence suggests that guidewire-assisted cannulation offers clinically meaningful advantages over contrast-assisted cannulation. In a systematic review and meta-analysis, guidewire-assisted cannulation was associated with a higher rate of primary selective biliary cannulation (85.4% vs 78.4%), a lower frequency of inadvertent pancreatic duct manipulation (37.1% vs 43.1%), and a reduced incidence of PEP (3.7% vs 7.7%) compared with contrast-assisted techniques [4]. Since its introduction, guidewire-assisted biliary cannulation has been increasingly adopted and is now widely regarded as the standard initial maneuver for selective biliary cannulation in ERCP [5,6].

Guidewire performance is influenced by multiple design features, including tip flexibility and configuration, the type and extent of hydrophilic coating, shaft stiffness, and maneuverability [7-9]. Even among guidewires of identical diameter, these characteristics can substantially affect cannulation behavior and overall procedural performance [10]. Accordingly, this study was performed to compare a newly developed guidewire with a widely used conventional guidewire in terms of clinical efficacy and safety.

METHODS

1. Study design and population

This was a prospective, multicenter, randomized noninferiority trial conducted at three tertiary hospitals from December 2024 to July 2025. Patients aged ≥18 years with a native papilla and no prior history of ERCP who were scheduled to undergo ERCP for diagnostic or therapeutic indications were screened and considered eligible for enrollment. Patients were excluded if they had acute pancreatitis within 2 weeks before ERCP, established chronic pancreatitis, or duodenal stenosis of any cause that prevented passage of the duodenoscope. After written informed consent was obtained, the patients were randomly assigned in a 1:1 ratio, using computer-generated randomization, to either the test group (TargetSure; Koswire, Busan, Korea; Fig. 1) or the control group (Visiglide 2; Olympus, Tokyo, Japan) by opening a sealed, opaque randomization envelope. The study protocol was approved by the Institutional Review Board of each participating center (IRB No.: HDT 2024-04-009). Written informed consent was obtained from all patients before enrollment. This trial was also registered at cris.nih.go.kr (KCT0009650) in July 2024.

2. Endoscopic procedures

ERCP was performed using standard duodenoscopes (TJF/JF-260; Olympus or ED-580XT; Fujifilm, Tokyo, Japan) by experienced endoscopists with more than 5 years of ERCP experience. After randomization, a wire-loaded papillotome or standard catheter was used at the discretion of the endoscopists. Initial biliary access was attempted using standard wire-guided cannulation techniques. The type of guidewire (straight or curved) was selected according to the endoscopist’s preference. If initial cannulation was considered difficult (defined as a cannulation time of >5 minutes, more than five cannulation attempts, or at least one unintended pancreatic duct cannulation), rescue techniques—including the double-guidewire method, pancreatic sphincterotomy, and infundibulotomy—were permitted.

3. Study outcomes and definition

The primary outcome of this study was the selective biliary cannulation success rate, defined as successful insertion of the guidewire into the intended bile duct.

Secondary endpoints included cannulation time, the incidence of difficult cannulation, and adverse events such as PEP, procedure-related perforation, and bleeding. Difficult cannulation was defined as a cannulation time of >5 minutes, more than five cannulation attempts, or at least one unintentional pancreatic duct cannulation.

PEP was defined according to internationally accepted criteria as new or worsened abdominal pain consistent with pancreatitis, accompanied by serum amylase and/or lipase levels >3 times the upper limit of normal at >24 hours after ERCP, requiring hospitalization for at least 48 hours [11]. The severity of ERCP-related adverse events, including PEP, was assessed using the Cotton consensus criteria, as referenced in major guidelines, including those of the European Society of Gastrointestinal Endoscopy [11]. Perforation was defined according to the American Society for Gastrointestinal Endoscopy (ASGE) adverse event lexicon as a full-thickness defect of the gastrointestinal or pancreaticobiliary wall related to ERCP, demonstrated by direct endoscopic visualization, extraluminal contrast leakage, extraluminal guidewire passage, or radiologic evidence of free or retroperitoneal air, contrast, or luminal contents outside the gastrointestinal tract on fluoroscopy, radiograph, or computed tomography. Bleeding was defined as ERCP-related bleeding that was clinically evident (e.g., hematemesis, melena, hematochezia) or associated with a hemoglobin drop of ≥2 g/dL and/or requiring blood transfusion, endoscopic, radiologic, or surgical intervention, and/or hospitalization or prolongation of planned admission for hemostasis, consistent with the ASGE lexicon for endoscopic adverse events [12].

4. Statistical analysis

The study was designed as a noninferiority trial. Assuming a selective biliary cannulation success rate of 92% in both groups, a non-inferiority margin of -11 percentage points, 80% power, and a one-sided significance level of 0.025, the required sample size was calculated to be 96 patients per group. Allowing for a 3% dropout rate, a total of 198 patients were planned for enrollment.

For the primary endpoint, non-inferiority was assessed using the absolute between-group difference in selective biliary cannulation success rates, calculated as the test group minus the control group. A two-sided 95% confidence interval (CI) for the between-group difference was calculated using the Newcombe method based on Wilson score intervals. Non-inferiority was concluded if the lower bound of the 95% CI was greater than the prespecified noninferiority margin of -11 percentage points.

Continuous variables were analyzed using Student’s t-test or the Mann–Whitney U test, as appropriate. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. A two-sided p-value of <0.05 was considered statistically significant for secondary and exploratory comparisons.

RESULTS

1. Baseline characteristics

In total, 198 patients were enrolled and included in the analysis (test group, n=98; control group, n=100). Baseline demographic and clinical characteristics were well balanced between the two groups, with no significant differences in age (63.7±16.1 years vs. 67.5±15.0 years, p=0.094), sex (p=0.573), body mass index (p=0.990), history of acute pancreatitis (p>0.999), or initial laboratory values, including total bilirubin and liver enzymes (Table 1). Procedural indications were also similar, with malignancy accounting for 27.6% and 35.0% of cases in the test and control groups, respectively (p=0.461).

2. Procedural characteristics

The procedural characteristics are summarized in Table 2. The prevalence of periampullary diverticulum was similar between the test and control groups (25.5% vs. 33.0%, p=0.276), and surgically altered anatomy was uncommon in both groups (0.0% vs. 2.0%, p=0.498). Initial cannulation devices were comparable, with no significant differences in the use of standard catheters (33.7% vs. 35.0%, p=0.882) or sphincterotomes (70.4% vs. 68.0%, p=0.759). The frequencies of rescue cannulation techniques, including the double-guidewire method (23.5% vs. 21.0%, p=0.734), rescue infundibulotomy (11.2% vs. 4.0%, p =0.064), and primary infundibulotomy (2.0% vs. 0.0%, p =0.244), did not differ significantly between the groups. In addition, subsequent endoscopic interventions such as pancreatic duct injection, pancreatic sphincterotomy, endoscopic papillary balloon dilation, endoscopic sphincterotomy, endobiliary biopsy, biliary stent placement, and pancreatic stent placement were performed at similar rates in both groups (all p>0.05).

3. Technical and clinical outcomes

Selective biliary cannulation was successful in 97 of 98 patients in the test group and 96 of 100 patients in the control group, yielding success rates of 99.0% and 96.0%, respectively. The absolute between-group difference in the success rate was 3.0 percentage points, calculated as the test group minus the control group, with a 95% CI of -2.2 to 8.9 percentage points. Because the lower bound of the CI was above the prespecified non-inferiority margin of -11%, the test guidewire met the criterion for non-inferiority with respect to the primary endpoint (Table 3). With respect to intraprocedural outcomes, difficult cannulation occurred significantly more frequently in the test group than in the control group (29.6% vs. 15.0%, p=0.017). The mean selective biliary cannulation time was significantly longer in the test group than in the control group (5.7 vs. 3.4 minutes, p=0.011).

The total procedure time did not differ significantly between the groups, although it was numerically longer in the test group (20.7 vs. 18.6 minutes, p=0.225). The incidence of the primary adverse event, PEP, was 5.1% (5/98) in the test group and 4.0% (4/100) in the control group, with no significant between-group difference (p=0.746). The distribution of PEP severity was also comparable between the groups (p=0.919). The rate of hyperamylasemia did not differ significantly between the test and control groups (16.3% vs. 9.0%, p=0.138). No procedure-related perforation or bleeding occurred in either group. The mean length of hospital stay was 6.0 days in the test group and 7.8 days in the control group (p=0.107).

DISCUSSION

This study compared the clinical efficacy, safety, and technical performance of a novel guidewire for selective biliary cannulation with those of a conventional guidewire widely used in clinical practice.

In this multicenter randomized non-inferiority trial, the novel guidewire met the prespecified criterion for non-inferiority with respect to selective biliary cannulation success. The success rate was 99.0% in the test group and 96.0% in the control group, corresponding to an absolute between-group difference of 3.0 percentage points and a 95% CI of -2.2 to 8.9 percentage points. Because the lower bound of the CI was above the prespecified non-inferiority margin of -11%, the primary endpoint supported the noninferiority of the novel guidewire compared with the conventional guidewire.

However, difficult cannulation occurred more frequently in the test group (p=0.017). This finding may be partly explained by the longer cannulation time in the test group (5.7 vs. 3.4 minutes; p =0.011) because a cannulation time exceeding 5 minutes constituted one of the criteria for difficult cannulation. Bench testing of commercially available 0.025-inch guidewires demonstrated that VisiGlide 2, used as the control in this study, exhibited the highest tip load and bending force among comparators, along with relatively low tip friction (0.18 N) and a thin hydrophilic coating layer (3.18 μm) [10]. These features may be advantageous for lesion entry and for maintaining access during device exchange [10]. Park et al. [13] reported that use of the highly flexible-tip VisiGlide 2 guidewire significantly reduced both the mean cannulation time and the number of papillary attempts compared with conventional 0.035-inch wires. The elongated tapered core at the distal tip of VisiGlide 2 provides optimal steerability and efficient torque control, which are essential for navigating tortuous ductal segments [8]. However, the relatively high bending force and tip load require careful manipulation to avoid iatrogenic injury, as guidewire-related perforations have been reported to account for up to 16% of such complications [7,14].

By contrast, the newly developed TargetSure guidewire offers distinct mechanical properties, characterized by superior elastic resiliency and a longer hydrophilic tip [15]. The TargetSure guidewire was designed with a longer and slightly smaller-diameter tip (80 mm and 0.57 mm) and showed greater elastic resiliency, but it also exhibited higher friction and lower tip stiffness than the conventional Jagwire in mechanical testing [15]. While its low tip stiffness suggests an atraumatic profile, the TargetSure group showed a higher frequency of ampulla contact and longer cannulation times compared with the control group [15]. These findings may be attributable to its higher friction coefficient and lower shaft stiffness, which could impair forward axial force transmission during challenging cannulation scenarios. This mechanical disadvantage is consistent with the higher incidence of difficult cannulation and the longer cannulation time observed in the test group in our study. Unlike prior studies that focused primarily on the mechanical properties and material characteristics of guidewires, based on in vitro testing, our study evaluated clinical efficacy and safety in real-world practice.

In the present study, the TargetSure guidewire achieved a selective biliary cannulation success rate that met the non-inferiority criterion compared with the conventional guidewire, VisiGlide 2. The observed rates of adverse events, including PEP, were similar between the groups, but these safety outcomes should be interpreted as secondary outcomes rather than as evidence of safety non-inferiority.

This study has several limitations. First, although this was a multicenter randomized trial, it was conducted at tertiary referral centers, and procedures were performed by experienced endoscopists, which may limit the generalizability of the findings to low-volume centers or less experienced operators. Second, blinding endoscopists to the type of guidewire was not feasible because of visible differences between devices, introducing a potential risk of performance bias. Third, although selective biliary cannulation success was evaluated, the study was not powered to detect small differences in individual adverse events, including PEP. Fourth, detailed mechanistic assessments of guidewire behavior during cannulation, such as in vivo measurements of pushability or torque transmission, were not performed; therefore, the proposed explanations regarding mechanical properties remain speculative. Fifth, user- and operator-reported outcomes, such as ease of use, tactile feedback, and overall satisfaction with the guidewires, were not formally assessed. Finally, although the guidewire tip configuration was selected according to the endoscopist’s preference, the straight or curved configuration used in each case was not prospectively recorded; therefore, we could not assess whether guidewire tip configuration influenced selective biliary cannulation success.

In conclusion, the novel guidewire achieved a selective biliary cannulation success rate that met the prespecified criterion for non-inferiority compared with the conventional guidewire. The between-group difference in success rate was 3.0 percentage points, and the lower bound of the 95% CI remained above the predefined non-inferiority margin of -11%. The novel guidewire also showed a comparable safety profile, without an increased risk of PEP or other procedure-related adverse events. However, the longer cannulation time and higher frequency of difficult cannulation in the test group suggest that further optimization of guidewire handling characteristics may be beneficial. Optimizing the coefficient of friction and shaft stiffness to potentially reduce the incidence of difficult cannulation remains a desirable objective for future iterations.

Notes

Conflicts of Interest

The authors have no conflicts to disclose.

AUTHOR CONTRIBUTIONS

Conceptualization: SWP, JHC; Data curation: EJK, HK, YHH, YSK, SYL, SIJ, KJL, DHK, JL; Formal analysis: EJK, SWP; Funding acquisition: SWP, JHC; Investigation: EJK, HK, SYL, SIJ, KJL, DHK, JL; Methodology: SWP, JHC, EJK; Project administration: SWP, JHC; Resources: all authors; Software: EJK; Supervision: JHC, SWP; Validation: EJK, JHC, SWP; Visualization: EJK; Writing–original draft: EJK; Writing–review & editing: all authors.

DATA AVAILABILITY

All data relevant to this study are included in the article and supplementary files. Additional de-identified data are available from the corresponding authors on reasonable request.

ACKNOWLEDGMENTS

The authors thank the investigators, study coordinators, and nursing staff at the participating centers for their support in patient recruitment, data collection, and conduct of this multicenter randomized trial. The authors also sincerely thank all patients who participated in this study.

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Fig. 1.

TargetSure guidewire. The novel guidewire is shown with an atraumatic straight distal tip (A), an elongated hydrophilic distal segment with a tapered transition zone (B), and a blue-coated shaft designed to provide visual distinction and procedural support during selective biliary cannulation (C).

Table 1.

Baseline characteristics and clinical variables

Variable	Test (n=98)	Control (n=100)	p-value
Male sex	49 (50.0)	54 (54.0)	0.573
Age (years)	63.7±16.1	67.5±15.0	0.094
Weight (kg)	63.0±13.3	64.1±13.7	0.570
Height (cm)	162.0±9.4	163.3±8.8	0.341
BMI (kg/m²)	23.8±3.5	23.8±3.6	0.990
History of pancreatitis	3 (3.1)	4 (4.0)	>0.999
Indication			0.461
Malignancy	27 (27.6)	35 (35.0)
Benign	69 (70.4)	64 (64.0)
Others	2 (2.0)	1 (1.0)
Initial laboratory values
WBC (/μL)	8,079±3,950	7,523±3,460	0.293
Hemoglobin (g/dL)	12.8±1.8	12.6±1.9	0.508
Platelet (×10³/μL)	217.3±89.6	223.7±78.6	0.597
PT (INR)	1.07±0.13	1.09±0.31	0.516
Total bilirubin (mg/dL)	4.4±5.9	5.0±6.7	0.546
AST (IU/L)	217.1±369.0	151.6±197.9	0.120
ALT (IU/L)	210.2±217.7	179.6±205.1	0.310
ALP (IU/L)	287.6±274.0	257.3±219.1	0.391
γGT (IU/L)	420.4±390.3	410.2±422.6	0.860
Amylase (IU/L)	195.9±666.1	133.4±497.9	0.466
Lipase (IU/L)	563.9±3,013.6	603.8±3,332.7	0.931

Values are presented as number (%) or mean ± standard deviation.

BMI, body mass index; WBC, white blood cell; PT, prothrombin time; INR, international normalized ratio; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; γGT, gamma-glutamyl transferase.

Table 2.

Procedural characteristics

Variable	Test (n=98)	Control (n=100)	p-value
Anatomical factors
Periampullary diverticulum	25 (25.5)	33 (33.0)	0.276
Surgically altered anatomy	0 (0.0)	2 (2.0)	0.498
Cannulation methods
Standard catheter	33 (33.7)	35 (35.0)	0.882
Sphincterotome	69 (70.4)	68 (68.0)	0.759
Double-guidewire method	23 (23.5)	21 (21.0)	0.734
Rescue infundibulotomy	11 (11.2)	4 (4.0)	0.064
Primary infundibulotomy	2 (2.0)	0 (0.0)	0.244
Interventions
Pancreatic duct injection	9 (9.2)	6 (6.0)	0.433
Pancreatic sphincterotomy	11 (11.2)	7 (7.0)	0.333
EPBD	35 (35.7)	27 (27.0)	0.221
EST	82 (83.7)	84 (84.0)	>0.999
Endobiliary biopsy	35 (35.7)	30 (30.0)	0.450
Biliary stent placement	59 (60.2)	61 (61.0)	>0.999
Pancreatic stent placement	26 (26.5)	22 (22.0)	0.509

Values are presented as number (%).

EPBD, endoscopic papillary balloon dilation; EST, endoscopic sphincterotomy; ERCP, endoscopic retrograde cholangiopancreatography.

Cannulation devices and techniques were not mutually exclusive. More than one cannulation device or technique could be used in a single patient during the same ERCP procedure; therefore, the sum of the categories may exceed the total number of patients in each group.

Table 3.

Technical and clinical outcomes

Variable	Test (n=98)	Control (n=100)	Between-group difference	95% CI
Selective biliary cannulation success	97 (99.0)	96 (96.0)	3.0 percentage points	-2.2 to 8.9

Variable	Test (n=98)	Control (n=100)	p-value
Technical outcomes
Difficult cannulation	29 (29.6)	15 (15.0)	0.017^*
Total procedure time (minutes)	20.7±13.1	18.6±11.8	0.225
Selective cannulation time (minutes)	5.7±7.4	3.4±5.1	0.011^*
24-hour post-ERCP laboratory values
WBC (/μL)	7,725.4±4,386.7	7,228.2±3,499.8	0.380
Hemoglobin (g/dL)	11.9±2.0	11.9±1.7	0.955
Platelet (×10³/μL)	204.8±81.7	211.2±74.0	0.567
Total bilirubin (mg/dL)	3.2±4.1	4.2±6.0	0.155
AST (IU/L)	112.8±155.3	103.2±112.9	0.620
ALT (IU/L)	160.9±161.7	142.4±132.4	0.379
ALP (IU/L)	257.2±232.0	245.9±201.7	0.714
γGT (IU/L)	357.6±301.0	374.6±361.7	0.720
Amylase (IU/L)	311.0±698.8	151.5±201.7	0.032^*
Lipase (IU/L)	967.6±3,209.2	387.2±850.5	0.091
Clinical outcomes
Length of hospitalization (days)	6.0±5.1	7.8±9.6	0.107
Post-ERCP pancreatitis	5 (5.1)	4 (4.0)	0.746
PEP severity			0.919
Mild	3 (3.1)	3 (3.0)
Moderate	1 (1.0)	1 (1.0)
Severe	1 (1.0)	0 (0.0)
Hyperamylasemia	16 (16.3)	9 (9.0)	0.138

Values are presented as number (%) or mean ± standard deviation.

WBC, white blood cell; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; γGT, gamma-glutamyl transferase; ERCP, endoscopic retrograde cholangiopancreatography; PEP, post-ERCP pancreatitis.

The between-group difference was calculated as the test group minus the control group. The prespecified non-inferiority margin was -11 percentage points. Non-inferiority was concluded because the lower bound of the 95% CI was greater than -11 percentage points. The 95% CI was calculated using the Newcombe method based on Wilson score intervals.

Difficult cannulation was defined as a cannulation time of >5 minutes, more than five cannulation attempts, or at least one unintentional pancreatic duct cannulation.

^* p<0.05.