Safety and Efficacy of Endoscopic Cardial Constriction Ligation （ECCL） With a Novel Disposable Endoscope: A Multicenter Randomized Controlled Trial
Phase: NA
Conditions: Gastroesophageal Reflux Disease (GERD)
Sponsor: Ying Zhu

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Safety and Efficacy of Endoscopic Cardial Constriction Ligation 
（ECCL） With a Novel Disposable Endoscope: A Multicenter Randomized 
Controlled Trial 
 
 
NCT Number：NCT ID not yet assigned 
2025-05-22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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I. Study Background 
Currently, traditional endoscopes are reusable, requiring cleaning and 
disinfection after each use before they can be reused. However, the inability to 
achieve complete sterilization with traditional endoscopes has garnered increasing 
attention [1,2]. In contrast, disposable endoscopes eliminate the risk of cross-
infection, bypass the cumbersome cleaning and disinfection processes, and reduce the 
incidence of surgical instrument-related infections. Furthermore, disposable 
endoscopes are comparable to standard endoscopes in terms of functionality and 
operability [3]. 
Gastroesophageal reflux disease (GERD) can be classified based on endoscopic 
findings into non-erosive reflux disease (NERD), reflux esophagitis (RE), and Barrett’
s esophagus (BE). Typical symptoms include heartburn and regurgitation, while 
atypical symptoms encompass chest pain, epigastric pain, abdominal bloating, 
belching, and extraesophageal symptoms [4]. Epidemiological surveys in China 
indicate a prevalence of heartburn occurring at least once weekly ranging from 1.9% 
to 7.0% [5,6]. Chronic, recurrent GERD significantly impairs patients’ quality of life 
and may increase the risk of Barrett’s esophagus, esophageal mucosal dysplasia, and 
esophageal adenocarcinoma. The pathogenesis and progression of GERD involve 
multiple factors, including increased esophageal acid exposure, lower esophageal 
sphincter (LES) relaxation, low esophagogastric junction (EGJ) pressure, impaired 
esophageal clearance, hiatal hernia, and damage to the mucosal barrier by cytokines 
(e.g., IL-6, IL-8, platelet-activating factor PAF) and heightened reflux sensitivity 
[7,8]. 
The first-line treatment for GERD currently involves lifestyle modifications and 
oral acid-suppressive medications, such as proton pump inhibitors (PPIs) [9] and 
potassium-competitive acid blockers (P-CABs) [10]. However, some patients with 
refractory GERD require long-term acid-suppressive therapy, and studies suggest that 

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prolonged PPI use may increase the risk of Clostridioides difficile infection, 
community-acquired pneumonia, gastric cancer, and chronic kidney disease [11,12], 
while short-term P-CAB use may lead to hypergastrinemia [13]. According to the 
2020 Chinese GERD Expert Consensus [14], for patients with refractory GERD who 
fail medical therapy, endoscopic or surgical treatment may be considered after 
thorough evaluation to rule out other causes and confirm evidence of reflux, with 
careful consideration of risks and benefits. 
Endoscopic cardia constriction ligation (ECCL), first performed by Professor 
Linghu Enqiang in 2013 [15], operates on principles similar to esophageal and gastric 
variceal ligation. Specifically, under direct endoscopic visualization, the mucosa and 
partial muscle layer above the dentate line are ligated to form folds. Post-ligation, the 
local mucosa undergoes ischemic necrosis and heals to form scar tissue, reducing the 
cardia diameter, increasing LES pressure, and alleviating reflux symptoms [16,17]. 
This method is characterized by simple operation and minimal invasiveness, making it 
safer than traditional surgical or laparoscopic procedures. Related complications, such 
as bleeding after ligation band detachment and retrosternal pain, have a low incidence 
and rapid recovery, with no severe adverse events reported to date. However, the long-
term efficacy of ECCL requires further validation through prospective, large-scale 
studies. 
In recent years, endoscopic treatments for refractory GERD have continued to 
evolve, but there are currently no studies on the efficacy and adverse event rates of 
ECCL performed using disposable endoscopes. Therefore, this study aims to conduct 
a randomized controlled trial to compare the effectiveness, safety, flexibility, and 
imaging clarity of ECCL guided by disposable versus traditional endoscopes in a large 
sample. The ultimate goal is to optimize treatment strategies, provide scientific 
evidence for personalized GERD treatment, and inform the development of future 
GERD treatment guidelines. 
II. Study Objectives 

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1. 
Primary Objective: To compare the efficacy of endoscopic cardia 
constriction ligation (ECCL) using disposable endoscopes versus traditional 
endoscopes in the treatment of refractory gastroesophageal reflux disease 
(GERD). 
2. 
Secondary Objectives: 
① To evaluate the observation clarity, flexibility, and compatibility of 
disposable endoscopes with surgical consumables. 
② To assess the incidence of device failures and complications related to 
disposable endoscope-guided ECCL, such as mucosal injury, bleeding, and 
perforation. 
III. Study Endpoints 
1. 
Primary Endpoint: Comparison of the effectiveness of ECCL using 
disposable versus traditional endoscopes in alleviating GERD-related 
symptoms such as acid regurgitation and heartburn. 
Evaluation Method: 
o Pre-procedure: Patients undergo GERD-Q scoring and 
endoscopic examination to establish baseline symptoms and 
endoscopic findings. 
o 3 months post-procedure: Patients are assessed with GERD-Q 
scoring and queried about GERD-related symptoms and complications. 
o 6 months post-procedure: Follow-up with repeat GERD-Q 
scoring to compare changes in GERD-Q scores from baseline to post-
procedure. 
2. 
Secondary Endpoints: 
① Clinical Feasibility of ECCL with Disposable Endoscopes 
Evaluation Method: 

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o Feasibility is defined as the ability to successfully retroflex the 
endoscope behind the cardia, clearly visualize the dentate line, and 
perform ECCL with the ligation device securely mounted on the 
endoscope, effectively suctioning the gastric mucosa and smoothly 
releasing the ligation band. All abnormal findings in the endoscopic 
report must be photographically documented. 
o A procedure is deemed “feasible” if the entire endoscopic 
examination and treatment are completed without interruption due to 
endoscope-related issues. It is deemed “infeasible” if the procedure is 
terminated due to endoscope malfunctions. 
o Clinical feasibility rate = (Number of successfully completed 
cases ÷ Total number of participants) × 100%. 
② Effectiveness and Safety of ECCL with Disposable Endoscopes 
o Record the clarity of endoscopic images, flexibility, and 
compatibility of required consumables with the endoscope during the 
procedure. 
o Document any endoscope-related mucosal injury, 
gastrointestinal perforation, or significant bleeding during the 
procedure or within 1 hour post-procedure, as well as any surgery-
related adverse events (e.g., pain, bleeding, infection) post-procedure. 
③ Device Failure/Defect Rate 
o Observe and record any device malfunctions during the 
procedure, such as image interruption, water delivery blockage, or 
leakage. 
3. 
Safety Endpoints: 
Primary Safety Endpoints: 

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① Document any endoscope-related mucosal injury, gastrointestinal 
perforation, or significant bleeding during the procedure or within 1 hour post-
procedure, as well as any surgery-related adverse events (e.g., pain, bleeding, 
infection) and equipment failures (e.g., image interruption, water flow 
blockage, or leakage). 
Secondary Safety Endpoint: 
③ Procedural Stability: Assess the stability of participants’ blood pressure 
and heart rate during the procedure, record the number of cases with stable 
parameters, and calculate the stability rate. 
III. Study Design, Methods, and Procedures 
1. 
Study Design 
This clinical study is a randomized (1:1), multicenter, parallel-controlled 
clinical trial. A total of 46 patients will be recruited. Participating centers 
include Shenzhen Hospital of Southern Medical University, the 964th Hospital 
of the Joint Logistics Support Force, and the Army Medical Center. The trial 
employs a multicenter competitive enrollment approach, with each center 
recruiting participants based on available patient resources and enrollment 
pace until the total recruitment target is met. All enrolled patients will be 
randomized using a computer-generated random number table, managed by an 
independent statistician who ensures allocation concealment. After signing the 
informed consent form, patients meeting the inclusion/exclusion criteria will 
be randomly assigned in a 1:1 ratio to either the experimental group 
(undergoing ECCL with disposable endoscopes) or the control group 
(undergoing ECCL with traditional endoscopes). 
• 
Experimental Group: Participants randomized to the experimental 
group will undergo ECCL using disposable endoscopes. The procedure 
involves sequentially suctioning and ligating one band each on the lesser 
curvature, posterior wall, and greater curvature of the cardia, capturing the 

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mucosal and muscular layers. A hemostatic clip will be used to secure the base 
of the ligated tissue on the greater curvature. Six hours post-procedure, 
patients may consume lukewarm liquid or semi-liquid diets and continue acid-
suppressive therapy for two weeks. 
• 
Control Group: Participants randomized to the control group will 
undergo ECCL using traditional endoscopes, following the same procedure: 
sequentially suctioning and ligating one band each on the lesser curvature, 
posterior wall, and greater curvature of the cardia, capturing the mucosal and 
muscular layers, with a hemostatic clip securing the base of the ligated tissue 
on the greater curvature. Six hours post-procedure, patients may consume 
lukewarm liquid or semi-liquid diets and continue acid-suppressive therapy for 
two weeks. 
Each participant will be followed up via telephone and outpatient visits at 3 
months and 6 months post-procedure. 
2. 
Study Methods 
(1) Randomization 
In this study, patients meeting the inclusion/exclusion criteria will be 
randomly assigned in a 1:1 ratio to the experimental or control group. A 
computer-generated random number table will be used, managed by an 
independent statistician who ensures allocation concealment. 
(2) Blinding/Unblinding 
This study will be conducted in an open-label manner. Imaging evaluations and data 
analysis will be performed by medical professionals independent of the study to 
ensure objectivity. 
3. Study Procedures 
Trial Flowchart 

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Item 
Screening 
Period 
Procedure 
Day 
Follow-up 
Period 
Follow-up 
Period 
TIME 
-3 to 0 
Days 
During 
Procedure 
3 Months 
Post-
Procedure 
6 Months 
Post-
Procedure) 
Informed Consent 
X 
Demographics 
X 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
Laboratory Tests 
X 
Electrocardiogram 
X 
 
 
 
Endoscopy 
X 
Blood Pressure, 
Heart Rate 
X 
X 
GERD-Q Score 
X 
X 
X 
Adverse Events 
X 
X 
X 
Medication Use 
X 
 
 
 
 Remarks＜ 
• 
Laboratory test results from within 7 days prior to signing the 
informed consent form are acceptable. 
• 
Endoscopy results from within 6 months prior to signing the 
informed consent form are acceptable. 
 

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IV. Study Population 
Patients diagnosed with refractory gastroesophageal reflux disease (GERD) in 
accordance with the 2023 Chinese Guidelines for the Diagnosis and Treatment of 
Gastroesophageal Reflux Disease. 
1. 
Inclusion Criteria 
(1) Age 18–80 years; 
(2) Disease duration ≥6 months, with typical symptoms such as acid 
regurgitation and heartburn, and a confirmed diagnosis of GERD; 
(3) GERD patients whose symptoms are not relieved after 8 weeks of 
continuous double-dose acid-suppressive therapy; 
(4) Willing to participate in the study and have signed the informed consent 
form. 
2. 
Exclusion Criteria 
(1) Patients with precancerous lesions such as early esophageal cancer or 
Barrett’s esophagus >3 cm, or advanced upper gastrointestinal cancer 
identified on endoscopy; 
(2) Patients with hiatal hernia ≥2 cm, severe reflux esophagitis (LA-C or LA-
D grade), esophageal or gastric varices, esophageal ulcer or stenosis, or a 
history of esophageal or gastric surgery; 
(3) Patients with esophageal motility disorders such as achalasia or diffuse 
esophageal spasm, rheumatic diseases such as systemic sclerosis or Sjögren’s 
syndrome, or eosinophilic esophagitis; 
(4) Patients with a history of endoscopic or surgical anti-reflux procedures; 
(5) Patients with coagulation disorders, severe cardiopulmonary diseases, or 
inability to tolerate anesthesia, endoscopy, or treatment; 
(6) Women in the puerperium. 
3. 
Lifestyle Considerations  

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1. 
Smoking: Patients are advised to reduce or quit smoking to 
prevent exacerbation of LES relaxation and reflux. 
2. 
Alcohol Consumption: Avoid strong liquors and high-
alcohol-content beverages to reduce gastric acid secretion. 
3. 
Exercise: Avoid vigorous exercise post-procedure; low-
intensity activities such as walking or yoga are permitted. 
4. 
Diet: Avoid high-fat, spicy foods, and carbonated 
beverages; consume lukewarm liquid or semi-liquid diets for 2 weeks 
post-procedure. 
5. 
Prohibited Medications: Avoid NSAIDs, anticholinergic 
drugs, and prokinetic agents; if their use is necessary, patients must 
report to the study team for evaluation. 
6. 
Additional Treatments or Surgeries: If participants 
require other GERD-related treatments or surgeries, they must notify 
the study team and may be withdrawn from the trial. 
4. 
Screening Failure 
Definition: Screening failure refers to participants who, during the initial 
screening process, fail to meet the inclusion criteria or meet any exclusion 
criteria, thus being ineligible for randomization. 
Management Measures:  
1. 
Record Reasons for Screening Failure: Document the 
specific reasons for ineligibility, such as symptoms not meeting GERD 
diagnostic criteria or presence of diseases listed in the exclusion 
criteria. 
2. 
Inform Participants: Explain the screening results to 
participants who fail screening and provide appropriate alternative 

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treatment recommendations or information about other potential 
studies. 
3. 
Data Management: Data from participants who fail 
screening will not be included in the final study analysis but may be 
used to optimize future screening criteria or improve study design. 
4. 
Follow-up: For some participants who fail screening, if 
their symptoms change or they meet inclusion criteria after treatment, 
they may be reassessed for potential inclusion in the study. 
 
5. Recruitment and Retention Strategies 
This study will be conducted at Shenzhen Hospital of Southern Medical 
University, the 964th Hospital of the Joint Logistics Support Force, and the Army 
Medical Center. A total of 46 GERD patients meeting the inclusion criteria will be 
recruited through outpatient screening, inpatient referrals, social media 
announcements, and patient education seminars, and randomly assigned in a 1:1 ratio 
to the experimental and control groups. To enhance participant compliance and 
retention, the study team will maintain contact via telephone, email, and WeChat, 
providing reminders for post-procedure follow-ups and offering free follow-up visits 
and GERD-related health consultations. For patients with slow recovery post-
procedure, the study team will provide additional health guidance and psychological 
support. As this study involves GERD treatment, to ensure participant safety, minors 
and pregnant women will not be included. All participants must sign an informed 
consent form and be fully informed of the study’s objectives, methods, and potential 
risks. These measures aim to ensure the smooth conduct of the study while 
safeguarding participants’ rights and safety. 
6. Evaluation Metrics 

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(1) Efficacy Evaluation: 
Primary Endpoint: 
① Whether GERD-related symptoms such as acid regurgitation and heartburn are 
significantly alleviated post-procedure, quantified by changes in GERD-Q scores, Los 
Angeles (LA) classification, and Hill classification from baseline to post-procedure, 
and whether these changes are statistically significant. 
Secondary Endpoint: 
② Feasibility assessment of ECCL. Evaluation parameters include: 
• 
Image Clarity: 
(A) Good brightness, contrast, and clarity: Able to accurately identify the 
dentate line of the cardia. 
(B) Poor brightness, contrast, or clarity: Unable to identify the dentate line of 
the cardia. 
• 
Endoscope Flexibility: 
(A) Endoscope can be smoothly retroflexed. 
(B) Endoscope cannot be smoothly retroflexed. 
• 
Compatibility of Consumables with Endoscope: 
(A) Endoscope is compatible with ligation equipment, allowing smooth 
operation. 
(B) Endoscope is incompatible with ligation equipment, preventing operation. 
Assessment Criteria: If all parameters are rated “A,” the feasibility of ECCL 
is deemed “qualified.” If any parameter is rated “B,” it is deemed 
“unqualified.” 
Feasibility Rate Calculation: (Number of “qualified” cases / Total number of 
patients per group) × 100. 
(2) Safety Evaluation: 
Primary Endpoint: 

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① Document any endoscope-related mucosal injury, gastrointestinal perforation, or 
significant bleeding during the procedure or within 1 hour post-procedure, as well as 
any surgery-related adverse events (e.g., pain, bleeding, infection) and equipment 
failures (e.g., image interruption, water flow blockage, or leakage). 
Secondary Endpoint: 
③ Procedural Stability: Assess the stability of participants’ blood pressure and heart 
rate during the procedure, record the number of cases with stable parameters, and 
calculate the stability rate. 
V. Study Interventions 
1. 
Intervention Details 
This study employs disposable and traditional endoscopes to perform 
endoscopic cardia constriction ligation (ECCL) to evaluate their safety and 
efficacy. The experimental group undergoes ECCL using disposable 
endoscopes, while the control group uses traditional endoscopes, both 
following a standardized procedure. This includes sequential suction and 
ligation of one band each on the lesser curvature, posterior wall, and greater 
curvature of the cardia, capturing the mucosal and muscular layers, with a 
hemostatic clip securing the base of the ligated tissue on the greater curvature. 
All participants receive post-procedure acid-suppressive therapy with oral 
proton pump inhibitors (PPIs) or potassium-competitive acid blockers (P-
CABs) and begin consuming lukewarm liquid or semi-liquid diets 6 hours 
post-procedure. Follow-ups at 3 and 6 months post-procedure assess GERD-Q 
scores, symptom relief, and complication rates, conducted via telephone, 
WeChat, or outpatient visits to ensure data completeness and participant 
compliance. 
2. 
Preparation/Handling/Storage/Responsibilities 
This study involves disposable gastrointestinal endoscopes as investigational 
medical devices, requiring strict management of storage, transportation, and 

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distribution. The storage conditions for these devices are 5°C–30°C with 
relative humidity ≤93%, and temperature and humidity records must be 
maintained during hospital storage to ensure a suitable environment. Device 
transportation is conducted via courier, managed by the study team, with 
conditions set at -40°C to 55°C and relative humidity ≤93%. Upon arrival at 
the hospital, handover procedures must be completed, and devices should be 
promptly stored. 
For device allocation, the experimental and control groups use disposable and 
traditional endoscopes, respectively, for ECCL. All device assignments are 
determined through a randomized design with allocation concealment 
managed by an independent statistician to ensure scientific rigor and 
impartiality. During the procedure, participants’ vital signs, procedural 
success, device compatibility, and any device-related adverse events must be 
meticulously recorded and included in the study analysis. 
Additionally, the study team must ensure the safe use of devices and provide 
standardized training to all medical staff to ensure consistency in clinical 
operations. Any equipment malfunctions or abnormalities during use must be 
immediately documented and reported to the study team to ensure the smooth 
conduct of the study. 
3. 
Concomitant Treatments 
During the study, participants may use acid-suppressive drugs (PPIs or P-
CABs), analgesics (acetaminophen), prokinetic agents (mosapride or 
domperidone), and antibiotics (cephalosporins or quinolones) under medical 
guidance to optimize post-procedure recovery and ensure scientific validity. 
Probiotics may be supplemented to maintain gut health, dietary adjustments 
made to avoid gastric acid stimulation, and psychological interventions 
applied to alleviate post-procedure anxiety. All concomitant treatments must 
be documented to ensure data comparability and objectivity. 

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4. 
Emergency Rescue 
In case of emergencies requiring rescue, medical staff may employ targeted 
medications and treatments, including norepinephrine, ephedrine, or dopamine 
to elevate blood pressure; desmopressin, thrombin, or blood transfusion to 
control severe bleeding; endoscopic titanium clips to close small perforations 
or surgical intervention for larger perforations; naloxone, endotracheal 
intubation, or mechanical ventilation for respiratory depression or asphyxia; 
and aspirin, nitroglycerin, or necessary cardiac interventions for myocardial 
infarction. During rescue, intravenous access must be established, and vital 
signs monitored in real-time using a multifunctional electronic monitor. 
Cardiopulmonary resuscitation (CPR) should be performed if necessary, with 
the emergency team intervening and transferring the patient to the ICU for 
further treatment. All rescue procedures must be thoroughly documented, 
including rescue timing, changes in condition, drug dosages, patient responses, 
monitoring data, surgical interventions, and imaging results, to ensure data 
completeness and traceability. 
VI. Study Intervention Suspension/Participant Termination and 
Withdrawal 
1. 
Study Intervention Suspension 
The study may be temporarily suspended under the following circumstances: 
if serious safety issues arise, such as gastrointestinal perforation, significant 
bleeding, or severe infection, with an adverse event rate exceeding the preset 
threshold, or if significant flaws in the clinical trial protocol are identified, 
rendering it difficult to evaluate the safety and efficacy of the investigational 
device. Additionally, suspension may occur if regulatory authorities determine 
that participant rights cannot be guaranteed or if adjustments to the study 
design are required. 
The duration of suspension will depend on the specific circumstances, ranging 

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from a short-term pause (e.g., 1–2 weeks) for adjustments to permanent 
termination. During suspension, data collection from enrolled participants will 
continue, including symptom relief, adverse event rates, and other relevant 
metrics, to assess the impact of suspension on data integrity. 
Resumption of the study requires resolution of critical issues affecting safety 
or scientific validity, such as optimizing device use, refining procedural 
protocols, or improving follow-up plans. Resumption must be approved by the 
ethics committee and regulatory authorities. 
During suspension, follow-up of participants will continue as per the original 
schedule, with symptom assessments and safety monitoring conducted via 
telephone, WeChat, or outpatient visits. If participants experience adverse 
reactions or medical needs, the study team will provide medical guidance or 
recommend appropriate treatment to ensure participant safety. 
2. 
Participant Termination/Withdrawal from the Study 
Criteria for Study Termination (the study will be terminated if any of the 
following apply): 
1. 
Serious safety issues occur during the trial; 
2. 
Significant errors are identified in the clinical trial protocol; 
3. 
The study sponsor requests termination of the trial; 
4. 
The ethics committee requests termination of the trial; 
5. 
The device regulatory authority requests termination of the trial. 
Participants who withdraw from the study for any reason must have the reason 
documented, including but not limited to: 
1. 
Withdrawal of informed consent by the participant; 
2. 
Termination of the study by the sponsor; 

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3. 
Severe adverse events preventing the participant from continuing in 
the trial; 
4. 
Significant protocol violations/deviations; 
5. 
Pregnancy; 
6. 
Poor compliance; 
7. 
Loss to follow-up; 
8. 
The investigator and/or sponsor determines that the participant’s 
medical condition may jeopardize their safety or that continued participation 
could harm their health. 
3. 
Loss to Follow-Up 
To minimize loss to follow-up and reduce the impact of missing data, the 
study team will emphasize the importance of follow-up to participants at the 
outset, provide clear scheduling, and use multiple communication methods 
(telephone, WeChat, email) to regularly remind participants of follow-up 
visits. Participants will be required to provide at least two alternative contacts 
to maintain communication in case of disconnection, ensuring data 
completeness. Additionally, the study team will offer remote follow-up 
options, such as online video or telephone interviews, and flexibly adjust 
follow-up schedules to reduce loss due to distance or time constraints. For 
occasional missing data, supplementation may be achieved by reviewing past 
medical records, interviewing participants, or consulting family members. In 
statistical analyses, missing data will be addressed using intention-to-treat 
(ITT) analysis or imputation methods to minimize the impact of loss to follow-
up on study results. 
 
VII. Detailed Study Procedures 

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1. 
All participants must sign an informed consent form prior to 
screening, and those who successfully pass the screening may proceed to 
enroll in the study. 
2. 
Participants are treated according to the protocol, with the 
experimental group undergoing endoscopic cardia constriction ligation 
(ECCL) using disposable endoscopes and the control group undergoing ECCL 
using traditional endoscopes. 
3. 
During the procedure, both the experimental and control groups are 
evaluated and documented for vital signs, procedural success (clinical 
feasibility of ECCL), endoscopist’s operational experience, and occurrence of 
device-related adverse events. 
4. 
At 3 and 6 months post-procedure, the efficacy and incidence of 
complications are evaluated and recorded. 
1. Screening Period 
All participants must complete the screening period assessments before enrollment, 
adhering to the inclusion and exclusion criteria. 
(1) Sign the informed consent form. 
(2) Record demographic data: date of birth, sex, and initials. 
(3) Collect medical history and perform a physical examination (including vital signs, 
anal inspection, and digital rectal examination). 
(4) Conduct laboratory tests, including complete blood count, coagulation profile 
(four items), and infectious disease panel (eight items). 
(5) Pre-procedure assessments: electrocardiogram, Los Angeles (LA) classification 
for reflux esophagitis, and Hill classification for hiatal hernia via endoscopy. 
2. Treatment Period 
Treatment modalities are determined based on pre-procedure randomization. 
• 
Experimental Group: Participants undergo ECCL using disposable 

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endoscopes. The procedure involves sequentially suctioning and ligating one 
band each on the lesser curvature, posterior wall, and greater curvature of the 
cardia, capturing the mucosal and muscular layers, with a hemostatic clip 
securing the base of the ligated tissue on the greater curvature. Six hours post-
procedure, participants may consume lukewarm liquid or semi-liquid diets and 
continue acid-suppressive therapy for two weeks. Vital signs and any surgery-
related serious adverse events are recorded during the procedure for statistical 
analysis. 
• 
Control Group: Participants undergo ECCL using traditional 
endoscopes, following the same procedure: sequentially suctioning and 
ligating one band each on the lesser curvature, posterior wall, and greater 
curvature of the cardia, capturing the mucosal and muscular layers, with a 
hemostatic clip securing the base of the ligated tissue on the greater curvature. 
Six hours post-procedure, participants may consume lukewarm liquid or semi-
liquid diets and continue acid-suppressive therapy for two weeks. Vital signs 
and any surgery-related serious adverse events are recorded during the 
procedure for statistical analysis. 
3. Follow-up Period 
All participants are followed up until 6 months post-procedure. 
• 
At 3 months post-procedure, participants undergo GERD-Q scoring 
and are queried about GERD-related symptoms and complications via 
telephone or WeChat. 
• 
At 6 months post-procedure, participants continue to undergo 
GERD-Q scoring and are queried about GERD-related symptoms and 
complications via telephone or WeChat. 
• 
Participants experiencing symptoms such as bleeding, fever, or chest 
pain during the follow-up period must return to the hospital within 24 hours 

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for blood tests, chest CT, or endoscopic examination to determine the cause of 
complications. 
VIII. Observation, Recording, and Management of Adverse Events 
1. 
Definition of Adverse Events (AE) 
An adverse event (AE) refers to any unfavorable medical occurrence in a 
patient or participant following the administration of a study drug, regardless 
of whether a causal relationship with the treatment is established. Thus, an AE 
can include any unfavorable signs (including abnormal laboratory findings), 
symptoms, or diseases temporally associated with the use of the study drug, 
whether or not they are considered related to the study drug. AEs encompass 
both serious adverse events (SAEs) and non-serious adverse events. 
2. 
Definition of Serious Adverse Events (SAE) 
An SAE is defined as any medical occurrence during a clinical trial that results 
in hospitalization or prolongation of hospitalization, disability, impaired work 
capacity, life-threatening conditions, death, or congenital anomalies. SAEs 
include the following medical events: 
(1) Events leading to death; 
(2) Life-threatening events (defined as events posing an immediate risk of 
death at the time of occurrence); 
(3) Events requiring hospitalization or prolongation of hospitalization; 
(4) Events leading to permanent or severe disability, functional impairment, or 
loss of work capacity; 
(5) Congenital anomalies or birth defects; 
(6) Other significant medical events (defined as events that jeopardize the 
participant or require intervention to prevent any of the above outcomes). 
3. 
Recording, Collection, Reporting, and Management of Adverse 
Events 

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(1) Collection, Reporting, and Management of AEs 
All AEs related to the study protocol procedures, occurring from the time of 
signing the informed consent form until the initiation of the study drug, must 
be recorded in the electronic Case Report Form (eCRF). 
AE records should include: a description of the AE and all related symptoms, 
onset time, severity, duration, relationship to the study drug, measures taken, 
and final outcome. AEs must be documented using medical terminology, and 
if a participant’s symptoms and signs can be attributed to a single underlying 
cause, a diagnosis should be recorded whenever possible. Apart from disease 
progression-related metrics, all clinical events and clinically significant 
laboratory abnormalities should be managed in reference to the Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0. Treatment-
related adverse reactions will be recorded by the investigator. 
(2) Collection and Reporting of SAEs 
All SAEs occurring from the time of signing the informed consent form until 4 weeks 
after completion of the study drug administration, regardless of cause or relationship 
to the study drug, must be reported using the SAE report form. In the event of an 
SAE, the investigator must immediately implement appropriate treatment measures to 
ensure participant safety and report the SAE within 24 hours to the drug registration 
applicant, the National Medical Products Administration, the Provincial Food and 
Drug Administration, the ethics committee of the respective clinical trial center, and 
the Medical Administration Department of the Health Commission. The lead 
institution’s ethics committee must also be promptly notified. The initial report should 
include, to the extent possible, the following details: source of the report, study drug 
name, SAE name, onset time, severity, duration, relationship to the study drug, 
measures taken, and outcome. 
(3) Pregnancy 
Women of childbearing potential must use effective contraception methods during the 

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study period, minimizing the risk of contraceptive failure. Before enrolling women of 
childbearing potential, the investigator must inform them of the importance of 
avoiding pregnancy during the study and the potential risks of unintended pregnancy. 
Participants must sign the informed consent form to confirm that these issues have 
been discussed and fully understood. 
Pregnancy Testing Requirements: All women of childbearing potential must have 
negative blood pregnancy test results during the screening period and at baseline/day -
1. Investigators must also inform all women of childbearing potential to immediately 
report any suspected pregnancy (e.g., amenorrhea or delayed menstruation) to the 
study team during the trial. 
Pregnancy Reporting: If pregnancy or suspected pregnancy is identified during the 
administration of the study drug, the study drug must be discontinued. If pregnancy or 
suspected pregnancy is identified within 3 months after the last dose of the study 
drug, it must be documented and reported accordingly. 
(4) Severity Assessment of AEs 
Investigators will assess the severity of AEs based on the five-level criteria outlined in 
NCI CTCAE version 5.0: 
• 
Grade 1: Mild; asymptomatic or mild signs; clinical or diagnostic 
observations only, no medical intervention required. 
• 
Grade 2: Moderate; limited age-appropriate instrumental activities 
of daily living (e.g., cooking, shopping, phone use). 
• 
Grade 3: Severe or medically significant but not immediately life-
threatening; results in hospitalization or prolongation of hospitalization; 
disabling; limits self-care activities of daily living (e.g., bathing, dressing, 
eating, toileting, medication administration, but not bedridden). 
• 
Grade 4: Life-threatening, requiring urgent intervention. 
• 
Grade 5: Death related to the AE. 

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(5) Investigator Responsibilities During SAE Follow-Up 
Investigators must conduct appropriate examinations and treatments for SAEs based 
on clinical judgment, including necessary clinical laboratory tests and physical 
examinations. Any results from these examinations or additional updated information 
related to the SAE must be reported in follow-up reports, adhering to the same 
timeline and process as the initial report. 
IX. Data Management 
1. 
Data Management 
(1) Investigators must ensure that data are authentic, complete, and accurate. 
(2) Any corrections to trial records must be made by striking through the 
original entry, noting the corrected data alongside, providing a reason for the 
change, and including the investigator’s signature and date. Original records 
must not be erased or obscured. 
(3) Laboratory test items must be comprehensive and complete. 
2. 
Data Recording and File Storage 
Data related to participants in the Case Report Form (CRF) must be recorded 
using participant codes, and participants can only be identified by their code or 
initials. 
This trial uses Excel for data management. The process includes data entry, 
verification against source data, resolution of quality control data queries, and 
finally, data locking and export. After confirming that there are no outstanding 
data issues, all parties sign the database lock request form, and the data 
administrator locks the database. Once locked, the data administrator exports 
the analysis database and provides it to the statistical team for analysis. 
Locked data cannot be edited. Any issues identified after database locking 
must be addressed and corrected in the statistical analysis program upon 
confirmation. 

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X. Data Safety Monitoring 
The clinical study will establish a data safety monitoring plan based on the level 
of risk. All adverse events (AEs) will be meticulously documented, appropriately 
managed, and followed up until resolved or stabilized. Serious adverse events (SAEs) 
and unexpected events will be reported promptly to the ethics committee, competent 
authorities, sponsor, and drug regulatory authorities as required. The principal 
investigator will periodically review all AEs cumulatively and, if necessary, convene 
investigator meetings to assess the study’s risks and benefits. In double-blind trials, 
emergency unblinding may be performed to ensure participant safety and rights. 
XI. Statistical Analysis 
1. 
Sample Size Determination 
Based on previous studies, the symptom relief rate for GERD patients 
undergoing ECCL is 97%. A non-inferiority margin of 0.25 is set, with an 
estimated loss to follow-up rate of 5%. It is calculated that each group requires 
23 patients (α = 0.05, β = 0.20). 
2. 
Definition and Selection of Analysis Sets 
• 
Full Analysis Set (FAS): The set of all participants who are 
enrolled, receive at least one dose of the study intervention, and have at least 
one efficacy assessment. 
• 
Safety Set (SS): The set of all participants who are enrolled, receive 
at least one dose of the study intervention, and have at least one safety 
assessment. 
• 
Per Protocol Set (PPS): The subset of the FAS consisting of 
participants who complete the protocol-specified treatment without significant 
protocol violations. 
3. 
Statistical Methods 

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The analysis will include the distribution of cases, demographic and baseline 
characteristics, treatment feasibility and safety analysis, and efficacy analysis. 
4. 
Statistical Software and General Requirements 
• 
All statistical analyses will be performed using SPSS v26. 
• 
Continuous data will be described using mean, standard deviation, 
median, maximum, and minimum values. 
• 
Categorical data will be described using frequencies and 
percentages. 
• 
Primary endpoints (safety, efficacy, post-procedure outcomes, and 
complications) will be analyzed using the chi-square test. 
XII. Ethical Principles and Requirements for Clinical Research 
The clinical study will adhere to the Declaration of Helsinki by the World 
Medical Association and the Ethical Review Measures for Biomedical Research 
Involving Humans by the National Health and Family Planning Commission of the 
People's Republic of China, among other relevant regulations. Specifically, the study 
will implement principles and requirements related to informed consent, privacy 
protection, provision of free research participation and compensation, risk control, 
protection of vulnerable participants, and compensation for research-related harm. 
Before the study begins, the trial protocol must be approved by the Ethics Review 
Committee. Prior to enrollment, investigators are responsible for fully and 
comprehensively explaining the study’s objectives, procedures, and potential risks to 
participants or their legal representatives, and obtaining written informed consent. 
Participants should be informed that their participation is entirely voluntary, that they 
may refuse to participate or withdraw at any stage of the study without facing 
discrimination or retaliation, and that their medical care and rights will not be 
affected. The informed consent form must be retained as part of the clinical study 

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documentation, ensuring the protection of participants’ personal privacy and data 
confidentiality. 
XIII. Study Timeline 
• 
June 2025 – June 2026: Complete participant recruitment, 
randomization, and treatment. 
• 
July 2026 – June 2027: Complete follow-up and statistical data 
analysis. 
• 
July 2027 – June 2028: Complete manuscript writing. 
 
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