Efficacy and Safety of the RDI Mode in Endoscopic Submucosal Dissection: a Multicenter, Randomized Controlled Study
Phase: NA
Conditions: Endoscopic Submucosal Dissection (ESD)
Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Study Protocol 
Protocol ID：2025ZSLYEC-728 
Title: Efficacy and Safety of the RDI Mode in Endoscopic Submucosal Dissection: a Multicenter, 
Randomized Controlled Study 
Document date: 12,1, 2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Background and aim 
Conventional white-light endoscopy (WLE) is hampered by insufficient contrast when attempting 
to identify deep vessels and active bleeding sites; visibility drops further when blood pools or 
spurts obscure the field, resulting in significantly lower hemostatic efficiency. Red dichromatic 
imaging (RDI), a novel image-enhanced endoscopic modality, has recently been shown to improve 
the visualization of deep-lying vessels and bleeding points, shorten hemostasis time and 
potentially increase overall procedural efficiency. 
Although retrospective series have suggested that RDI may facilitate intra-operative bleeding 
control and better delineation of the submucosal plane during endoscopic submucosal dissection 
(ESD), high-level evidence from multicenter, randomized, controlled trials (RCTs) is lacking. No 
study has yet demonstrated superiority over WLE with respect to critical endpoints such as en-
bloc resection rate, procedure time, complication rate and operator mental workload. 
We therefore designed a multicenter RCT to systematically compare the efficacy and safety 
of full-procedural RDI with conventional WLE during ESD. 
 
Methods 
Study design: a multicenter, randomized controlled clinical trial. 
Location: The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Hospital 
of Chinese Medicine, Guangdong Second Provincial General Hospital 
The inclusion criteria: 
① Age ≥ 18 years. 
② Early gastric cancer or precancerous lesions, early esophageal cancer or precancerous lesions, 
or early colorectal cancer/polyps that meet ESD indications. 
③ ESD procedure to be performed at a participating center. 
④ Lesion diameter 20–60 mm. 
⑤ Written informed consent provided voluntarily. 
The exclusion criteria: 
① Foreigners. 
② Severe coagulopathy (platelet count <50×10⁹/L or INR >1.5), significant cardiopulmonary 
disease, or any other contraindication to endoscopic therapy. 

③ Imaging evidence of distant metastasis or lymph-node metastasis. 
Intervention 
Patients who met the inclusion and exclusion criteria were randomly assigned to either the RDI 
group or the conventional white-light endoscopy (WLE) group. In the RDI group, the submucosal 
dissection was performed entirely under RDI mode (white-light mode was allowed only for 
observation and marking). In the WLE group, the entire ESD procedure was completed with 
white-light mode without switching to RDI. All ESD procedures were performed by experienced 
endoscopists (≥300 previous ESD cases and formal RDI training, with ≥20 ESD cases performed 
under RDI mode). 
Outcome parameters 
The primary outcome parameter is the mean resection speed (mm²/min) achieved with RDI versus 
conventional WLE during ESD. 
The secondary outcome parameters are: complete resection (R0) rate, en-bloc resection rate, 
resection margin, number of intra-procedural bleeding episodes, intra-procedural blood loss, intra-
procedural hemostasis time, other intra-procedural adverse events, and post-procedural adverse 
events. 
The results will be analyzed in full analysis set, per-protocol set and safety set. 
After the overall analysis, all data will be stratified by lesion location and analyzed separately 
for esophageal, gastric, and colorectal subgroups. 
Definitions 
The mean resection speed is the result of resection area divided by the resection time. The 
resection area is defined as the area on the specimen-fixation board. The resection time is defined 
as the time from the first mucosal incision to complete dissection of the lesion. Adverse events 
included bleeding, perforation, infection, and so on, mentioned by Cotton et al. (Gastrointest 
Endosc. 1994;40:514-518). 
Sample Size  
Based on a pilot study of 20 cases at our center, the mean resection speed in the RDI group was 
27.2 ± 9.8 mm²/min versus 21.1 ± 12.2 mm²/min in the white-light group. 
Assuming H₀: no difference in mean resection speed between the two groups, and setting α = 
0.05 and power = 0.90, the required sample size is 71 lesions per arm (142 total). 

Allowing for a 10 % dropout rate, we plan to enroll 79 lesions per arm, yielding 158 lesions 
in total (each lesion requiring ESD is counted as one case, even if multiple lesions occur in the 
same patient). 
Randomization 
Stratified randomization by center. Random numbers generated in Excel by an independent 
statistician; sequentially numbered, sealed, opaque envelopes prepared and held by the third party. 
The envelopes constitute the allocation sequence; random numbers remain concealed from 
patients and endoscopists until the envelope is opened immediately before allocation. 
Blinding 
Patients will be blinded; operators and video reviewers cannot be blinded; pathologists will remain 
blinded. 
Statistical analysis 
All analyses were performed with SPSS version 26. Baseline characteristics were examined to 
assess balance across concentration groups. Normally distributed continuous variables are 
presented as mean ± SD and compared between groups using independent-samples t-tests; non-
normally distributed continuous variables are expressed as median (interquartile range) and 
compared with the Wilcoxon rank-sum test. Categorical rates were compared using the χ² test. A 
two-sided P < 0.05 was considered statistically significant.