Effectiveness of Acupuncture for Atrial Tachyarrhythmia Prevention After Catheter Ablation in Persistent Atrial Fibrillation Patients: a Prospective, Open-label, Randomized, Blank-controlled Trial
Phase: NA
Conditions: Atrial Fibrillation (AF)
Sponsor: Shanghai Zhongshan Hospital

Full English Translation of the Clinical Research Protocol and 
Statistical Analysis Plan 
Source document: Investigator-Initiated Interventional Clinical Research Protocol, Fudan University 
Zhongshan Hospital, Version V1.2, dated January 27, 2026. 
Note: This is a faithful English translation of the protocol text provided by the user. The bibliographic 
references are retained in their original citation format. 
Fudan University Zhongshan Hospital 
Investigator-Initiated Interventional Clinical Research Protocol 
Project Title (Chinese): Effectiveness of acupuncture for reducing recurrence after catheter ablation in 
patients with persistent atrial fibrillation: a prospective, open-label, randomized, blank-controlled study 
Project Title (English): Effectiveness of acupuncture for atrial tachyarrhythmia prevention after catheter 
ablation in persistent atrial fibrillation patients: a prospective, open-label, randomized, blank-controlled trial 
Study Site: Fudan University Zhongshan Hospital 
Principal Investigator: Baozhen Qi 
Sponsor: Fudan University Zhongshan Hospital 
Version Number: V1.2 
Version Date: January 27, 2026 
 
 

Version History / Revision History 
Document 
Version No. 
Version Date 
Reason for Revision and 
Summary of Changes 
Protocol 
V1.0 
September 1, 2025 
 
Protocol 
V1.1 
December 5, 2025 
In response to the 
review comment to 
“assess the accuracy of 
the sample size 
calculation,” the sample 
size calculation section 
was revised. 
Protocol 
V1.2 
January 27, 2026 
In accordance with the 
ethics pre-review 
comments, exploratory 
endpoints and EDC-
related statements were 
removed. 
Investigator’s Statement 
I will conscientiously fulfill the responsibilities of an investigator in accordance with Chinese GCP 
requirements, and will personally participate in or directly supervise this clinical study. I have read and 
confirmed this protocol and agree with its scientific validity and ethical acceptability. I will perform the 
relevant responsibilities required under Chinese laws and regulations, the Declaration of Helsinki, Chinese 
GCP, and this study protocol, and the study will not be implemented until approval has been obtained from 
the Academic Committee and the Ethics Committee. Unless measures must be taken to protect the safety, 
rights, and interests of the subjects, I will keep this study protocol confidential. 
Study Site: Fudan University Zhongshan Hospital 
Principal Investigator: Baozhen Qi 
Principal Investigator (Signature): Baozhen Qi 
Date of Signature: 2026.01.27 
Table of Contents 
Protocol Summary 
List of Abbreviations 
I. Research Background 
II. Study Objectives 
2.1 Primary Objective 
2.2 Secondary Objective 
III. Study Overview 

3.1 Overall Study Design and Plan 
3.2 Sample Size and Grouping Method 
3.3 Randomization and Blinding 
3.4 Study Flowchart 
IV. Study Population 
4.1 Inclusion Criteria 
4.2 Exclusion Criteria 
4.3 Withdrawal Criteria 
4.4 Exclusion After Enrollment 
V. Endpoints 
5.1 Primary Endpoint 
5.2 Secondary Endpoints 
5.3 Safety Endpoints 
5.4 Exploratory Endpoints (if applicable) 
VI. Study Procedures 
6.1 Study Steps and Related Assessments 
6.2 Investigational Drug (if applicable) 
6.3 Concomitant Medications and Treatment (if applicable) 
6.4 Dose Adjustment (if applicable) 
6.5 End of Study 
6.6 Early Termination or Suspension of the Study 
6.7 Clinical Observation, Follow-up, and Measures to Ensure Subject Compliance 
VII. Collection and Reporting of Adverse Events 
VIII. Data Management 
IX. Statistical Analysis 
9.1 Sample Size Estimation 
9.2 Definition and Selection of Analysis Sets 
9.3 Statistical Analysis of Study Data 
X. Study Ethics 
10.1 Ethics Committee Review 
10.2 Informed Consent 
XI. Confidentiality Measures 

XII. Expected Study Timeline and Completion Date 
XIII. References 
 
 

Protocol Summary 
Item 
Content 
Protocol Title 
Effectiveness of acupuncture for reducing 
recurrence after catheter ablation in patients with 
persistent atrial fibrillation: a prospective, open-
label, randomized, blank-controlled study. 
Study Objective 
The primary objective is to evaluate the preventive 
effect of electroacupuncture on recurrence of atrial 
tachyarrhythmias (recurrence of atrial 
fibrillation/atrial flutter/atrial tachycardia) after 
catheter ablation in patients with persistent atrial 
fibrillation. Secondary objectives include 
improvement in left heart structure and function, 
atrial fibrillation burden, and quality of life. 
Study Endpoints 
Primary endpoint: recurrence rate of atrial 
tachyarrhythmias at Month 12. 
Secondary endpoints: changes at Month 12 in left 
atrial diameter, LVEDD, LVESD, LVEF, atrial 
fibrillation burden, and AFEQT score. 
Overall Design 
Prospective, single-center, open-label, randomized, 
blank-controlled study. Block randomization will be 
implemented through a central system, with a 12-
month follow-up period. 
Sample Size 
The planned sample size is 120 subjects (60 per 
group), estimated based on the expected difference 
in recurrence rates (39.8% vs 16%) and a 15% 
dropout rate. 
Study Groups 
Simple block randomization will be used to allocate 
subjects 1:1 to the treatment group 
(electroacupuncture + standard medication) or the 
control group (standard medication). Block lengths 
will be random to avoid predictability. 
Inclusion/Exclusion Criteria 
Inclusion criteria: age 20–75 years, persistent atrial 
fibrillation, restoration of sinus rhythm after first 
catheter ablation, left atrial diameter <50 mm, and 
voluntary written informed consent. 
Exclusion criteria: cardiovascular events within the 
prior 3 months, severe valvular disease, 
hypotension, structural heart disease, malignancy, 
severe hepatic or renal dysfunction, 
pregnancy/lactation, or other diseases affecting 
compliance or safety. 
Intervention 
Starting on postoperative Day 2, the treatment 
group will receive electroacupuncture (Neiguan and 
Jianshi; low frequency 2 Hz; twice weekly for 5 
weeks) plus standard medication; the control group 
will receive standard medication alone. 
Concomitant medications will be recorded and 
safety will be monitored. 
Criteria for Withdrawal 
Voluntary withdrawal of informed consent; medical 
judgment that continued participation is not in the 
patient’s best interest; pregnancy or major protocol 

violations will lead to exclusion. 
Statistical Analysis Plan 
The primary analysis will be based on the FAS 
population (ITT principle), and the PPS will be 
used for sensitivity analysis. Endpoints will be 
analyzed using Kaplan–Meier curves, the log-rank 
test, and Cox models for recurrence; ANCOVA will 
be used to evaluate changes in echocardiographic 
parameters, atrial fibrillation burden, and QoL 
scores. P<0.05 will be considered statistically 
significant. 
List of Abbreviations 
Abbreviation 
Full Term 
AF 
Atrial Fibrillation 
AFEQT 
Atrial Fibrillation Effect on Quality of Life 
ANCOVA 
Analysis of Covariance 
CRF 
Case Report Form 
CRP 
C-reactive Protein 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
HR 
Hazard Ratio 
IL-6 
Interleukin-6 
ITT 
Intention-To-Treat 
LVEF 
Left Ventricular Ejection Fraction 
LVEDD 
Left Ventricular End-Diastolic Diameter 
LVESD 
Left Ventricular End-Systolic Diameter 
MMP-2 
Matrix Metalloproteinase-2 
NT-proBNP 
N-terminal pro-B-type Natriuretic Peptide 
PPS 
Per Protocol Set 
QoL 
Quality of Life 
RR 
Relative Risk 
SAS 
Statistical Analysis System 
SAE 
Serious Adverse Event 
TGF-β1 
Transforming Growth Factor Beta 1 
I. Research Background 
Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice, and its prevalence increases 
with age. Between 2014 and 2016, the prevalence of AF among the Chinese population aged over 45 years 
was 1.8%. Based on the data from China’s Seventh National Population Census in 2020, it is estimated that 
approximately 12 million individuals in China have AF [1]. AF significantly increases the risks of death, 
heart failure, stroke, cognitive impairment, and dementia, and severely affects patients’ quality of life [2,3]. 
Over the past two decades, the management of AF has improved substantially with the development of new 
drugs and advances in catheter ablation techniques; however, progress in understanding its mechanisms has 
stagnated, treatment efficacy remains limited, adverse effects persist, and the success rate of catheter ablation 
for persistent AF is only 50%–60% [4]. 

In traditional Chinese medicine, AF falls within the category of palpitations. Its pathogenesis is mainly 
attributed to imbalance of qi, blood, yin, and yang, resulting in qi stagnation, blood stasis, and phlegm 
turbidity obstructing the heart vessels. The sympathetic and parasympathetic nervous systems are considered 
concrete manifestations of yin and yang in traditional Chinese medicine [5]. Acupuncture is a simple, 
economical, and effective therapy. Through mechanisms such as improving the balance of autonomic 
nervous activity, it may be used to treat AF, effectively restore and maintain sinus rhythm, reduce recurrence 
after electrical cardioversion and catheter ablation, and is considered safe without obvious adverse reactions 
[6–8]. 
However, most current clinical studies of acupuncture for AF have small sample sizes, uncertainty regarding 
acupoint selection and needle retention time, and non-uniform evaluation indicators. Higher-quality 
evidence-based medical evidence is needed in the future to explore different acupuncture methods and 
acupoint selections so as to formulate the optimal acupuncture regimen for AF. Because the pathogenesis of 
AF remains incompletely understood, catheter ablation is expensive, the recurrence rate after surgery for 
persistent AF is high, and the medical burden on patients is substantial, while acupuncture may reduce 
recurrence after catheter ablation, further exploration and optimization of acupuncture regimens are 
warranted to prevent recurrence after catheter ablation for AF. 
Therefore, we plan to screen hospitalized patients undergoing catheter ablation for AF and randomly assign 
patients with persistent AF to receive acupuncture treatment, in order to observe its effect on recurrence of 
atrial tachyarrhythmias. Because this population is prone to recurrence of atrial tachyarrhythmias, these 
patients are considered suitable for participation in this study after catheter ablation, and the anticipated 
benefits are expected to outweigh the risks. 
II. Study Objectives 
The purpose of this trial is to evaluate the effectiveness of acupuncture treatment after catheter ablation in 
patients with persistent atrial fibrillation. 
2.1 Primary Objective 
To evaluate the preventive effect of acupuncture treatment on recurrence of atrial tachyarrhythmias 
(recurrence of atrial fibrillation/atrial flutter/atrial tachycardia) after catheter ablation in patients with 
persistent atrial fibrillation. 
2.2 Secondary Objective 
To explore the effects of acupuncture on improvement in left atrial diameter, left ventricular end-diastolic 
diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, atrial fibrillation burden, 
and quality of life (QoL) after catheter ablation in patients with persistent atrial fibrillation. 
III. Study Overview 
3.1 Overall Study Design and Plan 
This is a prospective, single-center, open-label, randomized, blank-controlled study. 

3.2 Sample Size and Grouping Method 
The planned sample size is 120 cases. A simple block randomization method will be used. An independent 
biostatistician will generate the random number sequence according to the total sample size and block size 
using SAS 9.4 software and allocate subjects 1:1 to the treatment group and the control group, i.e., a 
randomization allocation list with 60 subjects in each group. The randomization process and concealment 
will be completed by an independent statistical unit. 
Treatment allocation: After written informed consent has been obtained, all screening procedures and 
evaluations have been completed, and patient eligibility has been confirmed, the study center will obtain the 
subject identification number and treatment allocation from the randomization implementation unit. Starting 
on the second day after surgery, the treatment group will receive electroacupuncture (Neiguan and Jianshi; 
low frequency, 2 Hz; twice weekly for 5 weeks) and standard medication therapy, while the control group 
will receive standard medication therapy. Detailed information regarding treatment administration will be 
recorded in the case report form (CRF). 
All concomitant medications must be reported to the investigators and recorded in the concomitant 
medication section of the CRF. 
Patients’ safety will be closely monitored throughout the study period. 
3.3 Randomization and Blinding 
This study will use a simple block randomization method. An independent biostatistician will generate a 
random number sequence using SAS 9.4 software and assign subjects to the treatment group and control 
group at a ratio of 1:1. The block size will be randomly varied and kept confidential by the statistical team in 
order to avoid predictable allocation. The randomization allocation sequence will be maintained and 
implemented by an independent statistical unit. After subjects sign informed consent, complete screening, 
and are confirmed to meet the inclusion criteria, investigators will obtain group allocation information 
through the central randomization system. 
This study is an open-label design and will not be blinded. Electroacupuncture, as the intervention in the 
treatment group, is an adjunctive therapeutic approach. Although there is evidence supporting its safety, it is 
designated as the study intervention in order to further explore its effectiveness in preventing recurrence after 
catheter ablation for AF; therefore, blinding will not be implemented. All treatment procedures will be 
conducted by qualified physicians, whereas study-related data collection and endpoint adjudication will be 
completed by blinded assessors to control information bias. Treatment administration and concomitant 
medications will be documented in detail in the CRF, and safety monitoring will be conducted throughout the 
study. 
3.4 Study Flowchart 
Figure 1. Study design and flow. 
IV. Study Population 
4.1 Inclusion Criteria 
• Age 20–75 years; 

• Persistent atrial fibrillation; 
• First catheter ablation for atrial fibrillation and restoration of sinus rhythm after the procedure; 
• Left atrial diameter <50 mm; 
• Ability to understand the study, voluntary participation, and signed informed consent. 
4.2 Exclusion Criteria 
• Cardiovascular events (including stroke, transient ischemic attack, myocardial infarction, unstable angina, 
etc.) or cardiac surgery within the previous 3 months; 
• Two consecutive in-hospital measurements (5 minutes apart) showing systolic blood pressure <100 mmHg 
accompanied by symptoms of hypotension; 
• Severe valvular heart disease (severe structural heart disease such as moderate-to-severe aortic or mitral 
valve disease); 
• Women who are breastfeeding, pregnant, or planning pregnancy during the follow-up period; 
• Status after pacemaker implantation; 
• Second- or third-degree atrioventricular block; 
• Bifascicular or trifascicular block; 
• Acupuncture treatment for cardiovascular disease within the previous 3 months; 
• Any other serious disease or condition, including: malignancy; history of chronic infectious disease; renal 
impairment defined as estimated glomerular filtration rate (according to the CKD-EPI equation) <30 
mL/min/1.73 m² or the need for hemodialysis at screening; moderate or severe hepatic impairment (Child–
Pugh class B or C); anemia defined as hemoglobin <90 g/L; systemic disease requiring hormone therapy; 
severe cognitive impairment or dementia; alcohol abuse or drug abuse; expected survival <12 months; poor 
compliance or inability to provide informed consent; 
• Current participation in another interventional study. 
4.3 Withdrawal Criteria 
• The subject requests withdrawal of informed consent for any reason; 
• In the investigator’s medical judgment, continued participation is not in the patient’s best interest and the 
study should be discontinued for the patient. 
4.4 Exclusion After Enrollment 
• Subjects who violate the study inclusion criteria; 
• Subjects who meet protocol exclusion criteria; 
• Subjects who become pregnant or enter the breastfeeding period after signing informed consent. 

V. Endpoints 
5.1 Primary Endpoint 
At the end of Month 12, recurrence of atrial fibrillation/atrial flutter/atrial tachycardia in the treatment group 
and the control group. 
Recurrence of atrial fibrillation/atrial flutter/atrial tachycardia is defined as any symptomatic episode of atrial 
fibrillation, atrial flutter, or other re-entrant atrial tachycardia lasting at least 30 seconds as recorded by 
surface electrocardiogram or 24-hour Holter monitoring after the 3-month blanking period following catheter 
ablation. All episodes will be reviewed by two independent electrophysiologists who are blinded to patient 
identity and randomization group. 
5.2 Secondary Endpoints 
• Change in left atrial diameter (measured by transthoracic echocardiography) at Month 12 compared with 
baseline. 
• Change in left ventricular end-diastolic diameter (measured by transthoracic echocardiography) at Month 
12 compared with baseline. 
• Change in left ventricular end-systolic diameter (measured by transthoracic echocardiography) at Month 12 
compared with baseline. 
• Change in left ventricular ejection fraction (measured by transthoracic echocardiography) at Month 12 
compared with baseline. 
• Change in atrial fibrillation burden at Month 12 compared with baseline in the treatment and control groups. 
Atrial fibrillation burden is defined as the percentage of time in atrial fibrillation on 24-hour Holter 
monitoring. 
• Change in QoL score at Month 12 compared with baseline in the treatment and control groups. The atrial 
fibrillation-specific AFEQT questionnaire will be used to assess changes in QoL. AFEQT contains 21 items 
covering 4 domains: symptoms, daily activities, treatment concerns, and treatment satisfaction; 18 items are 
used to calculate the overall score, ranging from 100 (no AF-related disability) to 0 (complete AF-related 
disability). 
5.3 Safety Endpoints 
Because acupuncture treatment is considered safe and has no obvious adverse reactions, no formal safety 
endpoint is specified in this study. However, safety evaluation will include: 
• The nature, incidence, severity, and seriousness of adverse events; 
• Changes in vital signs, symptoms, and physical examination findings relative to randomization baseline; 
• Changes in clinical laboratory test results relative to randomization baseline. 
5.4 Exploratory Endpoints (if applicable) 
Not applicable. 

VI. Study Procedures 
6.1 Study Steps and Related Assessments 
6.1.1 Screening Phase 
6.1.1.1 Preliminary screening of potential subjects: 
Patients aged 20–75 years with persistent atrial fibrillation who are hospitalized in the cardiology ward of the 
study site and are scheduled to undergo first-time catheter ablation for atrial fibrillation will be preliminarily 
screened. 
6.1.1.2 Screening for enrollment: 
Potential subjects will be screened from the cardiology ward of the study center, and inclusion and exclusion 
criteria will be reviewed. Informed consent will be obtained before screening. 
For those who provide informed consent, the CRF will be completed further. Regardless of randomization 
group, the following baseline data will be collected: 
• Sociodemographic characteristics: sex, age, marital status, height, weight, etc.; 
• Medical history and medication use history; 
• Physical examination: blood pressure, heart rate, cardiac examination, etc.; 
• QoL assessment: AFEQT; 
• Instrumental examinations: 12-lead ECG, 24-hour Holter monitoring, transthoracic echocardiography, 
transesophageal echocardiography, pulmonary vein CTV; 
• Laboratory tests: complete blood count, blood glucose, blood lipids, liver and renal function, electrolytes, 
coagulation, cardiac troponin, NT-proBNP, etc. 
6.1.2 Enrollment Phase 
Randomization and allocation concealment: Subjects who sign informed consent will be randomized. Central 
randomization will be used in this study. According to random codes generated by SAS computer software, 
subjects will be randomized at a ratio of 1:1 to one of the two treatment groups. Randomization will use 
simple block randomization with variable block lengths. The randomization sequence will be generated and 
retained by an independent biostatistician. Investigators will obtain the randomization number and group 
assignment through the “randomization platform.” The randomization center computer system will 
automatically generate a randomization result list containing the patient number, randomization number, 
treatment assignment information, and randomization date for monitoring purposes. 
Blinding procedures: This is an open-label study. 
Dose and administration: Starting on the second postoperative day, patients in the treatment group will 
receive electroacupuncture (Neiguan and Jianshi; low frequency, 2 Hz; twice weekly for 5 weeks). Whether 
other antiarrhythmic drugs should be discontinued or added will be decided by the treating clinician. Patients 
in the control group will receive standard drug treatment (blank control) according to the physician’s 
judgment. 

Concomitant medication: All medications used during the study period (prescription or OTC) must be 
recorded in the corresponding section of the follow-up observation form. 
Compliance: Study personnel will maintain detailed records and coordination of medications for each subject 
during the study. 
6.1.3 Follow-up Phase 
Each enrolled subject will undergo the study visits shown in Table 1, with a total follow-up duration of 12 
months. Follow-up will be conducted by study personnel and research nurses who have received specialized 
education in the care of patients with atrial fibrillation and training on the study protocol. All patients will 
attend in-person visits at Months 1, 3, 6, and 12 after AF catheter ablation. Each visit will include: (1) 
whether any adverse events have occurred; (2) changes in concomitant medication (drug name and dosage); 
(3) physical examination, including blood pressure, heart rate, and body weight; (4) QoL assessment 
(AFEQT); (5) any AF-related symptoms and documented recurrence of arrhythmia; and (6) instrumental 
examinations (12-lead ECG, transthoracic echocardiography, and 24-hour Holter monitoring). Transthoracic 
echocardiography will be performed in the echocardiography laboratory of Zhongshan Hospital according to 
a standardized protocol and reviewed in a blinded manner. No additional biological sample collection or 
outsourced testing will be performed in this study. 
During follow-up, if the physician judges that AF is inadequately controlled, other antiarrhythmic drugs may 
be added at any time according to relevant guidelines. 
Table 1. Schedule of Assessments 
Assessment 
Screening 
1 Month 
3 Months 
6 Months 
12 Months 
Informed consent 
X 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
Sociodemographic 
characteristics 
X 
 
 
 
 
Disease and 
procedural history 
X 
 
 
 
 
Concomitant 
medication 
X 
X 
X 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
Cardiac physical 
examination 
X 
X 
X 
X 
X 
QoL assessment 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
X 
24-hour Holter 
monitoring 
X 
 
X 
X 
X 
Transthoracic 
echocardiography 
X 
 
X 
X 
X 
Transesophageal 
echocardiography 
X 
 
 
 
 
Pulmonary vein 
CTV 
X 
 
 
 
 
Complete blood 
count 
X 
 
 
 
X 
Fasting blood 
X 
 
 
 
X 

glucose 
Liver and renal 
function 
X 
 
 
 
X 
Electrolytes 
X 
 
 
 
X 
Blood lipids 
X 
 
 
 
X 
High-sensitivity 
troponin T 
X 
 
 
 
X 
NT-proBNP 
X 
 
 
 
X 
C-reactive protein 
X 
 
 
 
X 
Drug 
accountability 
 
X 
X 
X 
X 
Adverse events 
 
X 
X 
X 
X 
6.2 Investigational Drug (if applicable) 
Not applicable. 
6.3 Concomitant Medications and Treatment (if applicable) 
Not applicable. 
6.4 Dose Adjustment (if applicable) 
Not applicable. 
6.5 End of Study 
The end of study is defined as the time when all enrolled patients have completed the 12-month follow-up. 
6.6 Early Termination or Suspension of the Study 
The study may be terminated early or suspended under the following circumstances: unexpected, significant, 
or unacceptable risks to participants are identified; major protocol errors are found during study conduct; 
continuation of the study is deemed meaningless; etc. 
6.7 Clinical Observation, Follow-up, and Measures to Ensure Subject Compliance 
• A complete visit schedule (baseline and Months 1, 3, 6, and 12) will be provided to ensure that patients are 
informed; 
• The treatment group will receive 5 weeks of acupuncture treatment free of charge; 
• Safety follow-up will be completed for subjects who withdraw or are lost to follow-up. 
VII. Collection and Reporting of Adverse Events 
7.1 Definition of Adverse Events 
Adverse event: any unfavorable medical event occurring after a subject receives acupuncture treatment, 
which does not necessarily have a causal relationship with the treatment. 
Serious adverse event: any event occurring during participation in this study that requires hospitalization, 
prolongs hospitalization, causes disability, affects the ability to work, is life-threatening, or results in death. 

• Mild: tolerable to the subject, does not affect treatment, requires no special management, and has no effect 
on recovery. 
• Moderate: difficult for the subject to tolerate, requires special management, and has a direct impact on 
recovery. 
• Severe: life-threatening, fatal, or disabling, requiring immediate emergency treatment. 
7.2 Recording and Reporting of Adverse Events 
Clinical adverse events may occur during subject treatment. Once an adverse event occurs (including 
important adverse events), the time of onset, clinical manifestations, management process and duration, 
outcome, and relationship to acupuncture treatment will be recorded in detail in the case report form. If an 
abnormal laboratory finding occurs, the patient must be followed until the test result returns to normal, 
returns to the pre-acupuncture level, or is determined to be unrelated to the study intervention (acupuncture 
treatment). If a serious adverse event occurs, a serious adverse event form must be completed and reported 
within 24 hours after the event to the sponsor, the Ethics Committee, the National Medical Products 
Administration (NMPA), and the local health administrative authority. 
7.3 Risk Prevention and Management 
• Bleeding: local bleeding after needle withdrawal during follow-up generally can be stopped by compression; 
if persistent bleeding or similar symptoms occur, timely treatment will be provided. 
• Hematoma: local hematoma after needle withdrawal during follow-up; if hematoma occurs, prompt 
compression or other treatment will be provided. 
• Pain: pain during needle retention and after needle withdrawal during follow-up; if the pain is intolerable, 
treatment will be stopped if necessary and appropriate management will be provided. 
• Vasovagal reaction: factors that may cause vasovagal reactions will be evaluated before treatment. After 
treatment begins, heart rate and blood pressure will be monitored, along with signs and symptoms of 
vasovagal reaction. If a vasovagal reaction occurs, acupuncture will be stopped immediately and treatment 
will be given. Mild vasovagal reactions may be relieved by lying supine or appropriate fluid supplementation; 
severe cases may require intravenous atropine. 
• Infection: infection-related symptoms will be evaluated before treatment and monitored after treatment. If 
symptoms such as local redness, swelling, suppuration, or fever occur, the patient will seek medical attention 
promptly and receive appropriate treatment. 
VIII. Data Management 
8.1 Case Report Form Design and Data Collection (Case Report Form, CRF) 
This study will use paper case report forms (CRFs) for data collection. The CRFs will be designed strictly in 
accordance with the study endpoints and key data elements in the protocol to ensure complete and accurate 
recording of subject information, clinical assessment results, laboratory test results, and safety-related 
information required for the study. 
The main content modules of the CRF include: 

• Basic subject information: general demographic data such as age, sex, height, and weight; 
• Disease-related information: clinical data including AF history, previous diagnoses, treatments, and 
concomitant diseases; 
• Treatment and intervention records: detailed records of the acupuncture regimen, frequency, treatment 
course, and standard treatment; 
• Laboratory and imaging examination results: complete blood count, liver and renal function, cardiac 
biomarkers (such as cardiac troponin and NT-proBNP), ECG, echocardiography, etc.; 
• Adverse event records: detailed records of adverse events and serious adverse events occurring during the 
study, including time of occurrence, severity, management measures, and outcomes. 
The CRF will not collect directly identifiable personal information such as subjects’ real names, inpatient 
numbers, identity card numbers, or mobile phone numbers. Each subject will be identified only by a unique 
study number. 
8.2 Data Entry and Verification 
During the study, research personnel who have received uniform training will promptly enter relevant subject 
information into the paper CRF after each visit. To improve data accuracy and facilitate subsequent statistical 
analysis, research personnel will use password-protected electronic spreadsheets during the study to perform 
double entry of CRF data or to collate and summarize the data. The electronic data must be consistent with 
the paper CRF. 
The study team will regularly cross-check the paper CRFs against the electronic data. If inconsistencies or 
missing information are identified, they will be verified and corrected in a timely manner, and modification 
records will be retained in the CRF to ensure data integrity and accuracy. 
8.3 Data Review and Quality Control 
The principal investigator will organize the study team to conduct regular data review and quality control, 
focusing on completeness, consistency, and logical plausibility of the data. All modifications must be clearly 
documented, with the date of modification and the person making the modification specified. Important data 
will be verified by two-person review to reduce human error and ensure the reliability of the study data. 
8.4 Data Lock and Statistical Analysis 
After all subjects have completed follow-up and data review has been completed, the study team will 
perform final confirmation of the study data and lock the database. In principle, no modifications will be 
made after data lock. If modification is absolutely necessary, approval from the principal investigator must 
be obtained and a complete modification record must be retained. The locked dataset will be used for 
statistical analysis and preparation of the study report. 
8.5 Data Retention and Transfer 
After the study is completed, all paper CRFs will be uniformly organized, numbered, and stored centrally in 
a secure location designated by Fudan University Zhongshan Hospital. Electronic data will be stored in 
encrypted form on access-restricted computers or storage media and backed up regularly. 

For statistical analysis, the study data will be provided to statistical analysts in de-identified form, containing 
only study numbers and no information that can identify subjects. 
8.6 Data Security and Privacy Protection 
This study will strictly comply with relevant laws, regulations, and GCP requirements, and will adopt 
necessary administrative and technical measures to protect subject privacy. All study data will be managed 
using coded identifiers. Study team members may access study data only within the scope of their study 
responsibilities. Without approval from the Ethics Committee, study data must not be disclosed to irrelevant 
personnel or institutions. 
IX. Statistical Analysis 
9.1 Sample Size Estimation 
The sample size estimation is based on the primary study endpoint—the recurrence rate of atrial 
fibrillation/atrial flutter/atrial tachycardia within 12 months after catheter ablation. According to previous 
studies, the 12-month recurrence rate after catheter ablation in patients with persistent AF is approximately 
39.8% [9,10], corresponding to a sinus rhythm maintenance rate of approximately 60.2%. Data from a 
systematic review indicate that acupuncture treatment can significantly improve the restoration of sinus 
rhythm [8], with a pooled relative risk (RR) of approximately 1.40. Based on this, the sinus rhythm 
maintenance rate in the acupuncture combination group is estimated to reach approximately 84.3%, 
corresponding to an AF/atrial flutter/atrial tachycardia recurrence rate of approximately 15.7%. For the 
purpose of sample size estimation in this study, the recurrence rate in the acupuncture group is conservatively 
assumed to be 16%. 
With α=0.05, β=0.20, a two-sided test, and a 1:1 allocation ratio, using the sample size calculation method 
for comparing the difference between two proportions, the required sample size is 52 subjects per group. 
Considering an approximately 15% dropout rate, the final planned total sample size is 120 patients (60 per 
group). 
The planned enrollment is 120 subjects. Based on the clinical practice experience at the study center, among 
AF patients who undergo first-time catheter ablation and successfully restore sinus rhythm, approximately 89% 
are aged 20–75 years, approximately 68% have persistent AF, and approximately 81% have a left atrial 
diameter <50 mm. Taking inclusion and exclusion criteria together into account, approximately 30% of 
patients undergoing catheter ablation for AF are expected to be eligible for enrollment. Therefore, it is 
estimated that at least 400 eligible AF patients will need to be screened during the screening phase to identify 
potential study subjects and ensure enrollment of 120 subjects. 
Regarding the feasibility of study conduct, based on data from 2024, more than 450 patients at the study 
center met the eligibility criteria, which is sufficient to satisfy recruitment requirements. 
9.2 Definition and Selection of Analysis Sets 
The statistical analysis of this study will follow the ICH E9 guideline and the relevant requirements of the 
Biostatistical Guideline for Drug Clinical Trials issued by the National Medical Products Administration. 
Study data will be centrally managed and analyzed by the statistical team of Fudan University Zhongshan 
Hospital and the Shanghai Institute of Cardiovascular Diseases using SAS 9.4 statistical software. The 

primary analysis populations will include the Full Analysis Set (FAS) and the Per Protocol Set (PPS). The 
FAS will be constructed according to the Intention-to-Treat (ITT) principle and will include all randomized 
subjects who have received at least one intervention. The PPS will consist of the subset of subjects with good 
treatment compliance and no major protocol violations and will be used mainly for sensitivity analyses. 
Safety analyses will also be conducted in the FAS population. 
9.3 Statistical Analysis of Study Data 
1. Descriptive Statistics and Baseline Comparisons 
All baseline demographic and clinical variables will be presented using descriptive statistics. Continuous 
variables with a normal distribution will be expressed as mean ± standard deviation (SD), while continuous 
variables with a non-normal distribution will be expressed as median and interquartile range (IQR). 
Categorical variables will be presented as counts and percentages. Comparisons of baseline characteristics 
between groups will be performed using the independent-samples t-test, Wilcoxon rank-sum test, chi-square 
test, or Fisher’s exact test, as appropriate according to variable type. 
2. Primary Endpoint: recurrence rate of atrial fibrillation/atrial flutter/atrial tachycardia at Month 12 
A recurrence event is defined as an episode of atrial fibrillation, atrial flutter, or atrial tachycardia occurring 
after the post-ablation blanking period (3 months), lasting ≥30 seconds, diagnosed by ECG or 24-hour Holter 
monitoring, and independently confirmed by two blinded electrophysiology experts. Kaplan–Meier survival 
analysis will be used to plot event-free survival curves for recurrence, and the log-rank test will be used for 
significance testing. Comparisons of recurrence rates will be further analyzed using the Cox proportional 
hazards regression model to estimate the hazard ratio (HR) and its 95% confidence interval between the 
treatment group and the control group. The FAS will be the primary analysis set, and the PPS will be used 
for sensitivity validation. 
3. Secondary Endpoint Analysis 
All secondary endpoints are continuous variables, including changes in echocardiographic parameters (left 
atrial diameter, LVEDD, LVESD, LVEF), atrial fibrillation burden, and the QoL questionnaire AFEQT score, 
all compared between Month 12 and baseline. Analyses will be performed using an analysis of covariance 
(ANCOVA) model adjusted for pre-treatment baseline values and other important covariates. Results will be 
expressed as the difference in least-squares mean (LS-mean) changes between groups and the corresponding 
95% confidence intervals. 
4. Safety Analysis 
Safety analyses will include the frequency and proportion of adverse events (AEs) and serious adverse events 
(SAEs). Between-group comparisons will be performed using the chi-square test or Cochran–Mantel–
Haenszel test. The results will be summarized by treatment group and will describe the incidence of each 
type of AE and its possible association with the intervention. 
All statistical tests will be two-sided, and a P value <0.05 will be considered statistically significant. Unless 
otherwise specified, missing data will not be imputed and analyses will be performed on complete-case data. 

X. Study Ethics 
10.1 Ethics Committee Review 
This protocol, the written informed consent form, and materials directly related to subjects must be submitted 
to the Ethics Committee, and the study may formally begin only after written approval has been obtained 
from the Ethics Committee. The investigator must submit a continuing review report one month before 
expiration of the ethics approval letter to apply for renewal. Upon study suspension and/or completion, the 
investigator must notify the Ethics Committee in writing. The investigator must promptly report all changes 
occurring during the study (such as revisions to the protocol and/or informed consent form) to the Ethics 
Committee, and such changes must not be implemented before Ethics Committee approval is obtained, 
unless the change is necessary to eliminate an obvious and immediate risk to subjects. In such cases, the 
Ethics Committee will be notified. 
10.2 Informed Consent 
The investigator must provide the subject or the subject’s legal representative with an easily understandable 
informed consent form approved by the Ethics Committee, and must give the subject or legal representative 
sufficient time to consider participation in the study. Subjects must not be enrolled before written informed 
consent signed by the subject is obtained. During the subject’s participation, all updated versions of the 
informed consent form and written information will be provided to the subject. The informed consent form 
shall be retained as an important clinical trial document for inspection. 
XI. Confidentiality Measures 
The results of this study may be published in medical journals; however, patients’ personal information will 
be kept confidential in accordance with legal and regulatory requirements. Unless required by applicable law, 
patients’ personal information will not be disclosed. When necessary, government regulatory authorities, the 
hospital Ethics Committee, and related personnel may review patient data in accordance with regulations. 
XII. Expected Study Timeline and Completion Date 
The planned enrollment period is 1 year (January 1, 2026 to December 31, 2026), with a follow-up period of 
12 months. The latest study completion date is April 30, 2028. The total study duration is 28 months. 
XIII. References 
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survey of adults in China[J]. Heart, 2021, 107(7): 535‑541. 
2. Chinese Society of Cardiology, Chinese Society of Biomedical Engineering. Chinese guideline for the 
diagnosis and treatment of atrial fibrillation[J]. Chinese Journal of Cardiology, 2023, 51(6): 572-618. 
3. Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC Guidelines for the management of atrial 
fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery 
(EACTS)[J]. Eur Heart J, 2024, 45(36): 3314-3414. 

4. de Groot NMS, Kleber A, Narayan SM, et al. Atrial fibrillation nomenclature, definitions, and 
mechanisms: Position paper from the international Working Group of the Signal Summit[J]. Heart Rhythm, 
2025, 22(6): 1480-1491. 
5. Takahashi T. Mechanism of acupuncture on neuromodulation in the gut--a review[J]. Neuromodulation, 
2011, 14(1):8-12; discussion 12. 
6. Huang Dan, Li Jianhua, Gan Taomei. Current status of traditional Chinese medicine treatment for atrial 
fibrillation[J]. China’s Modern Distance Education of Traditional Chinese Medicine, 2024, 22(17):84-86. 
7. Zhang Xuesong, Wei Yi, Yuan Guozhen, et al. Bibliometric study on acupuncture treatment of 
arrhythmia[J]. Anhui Medical and Pharmaceutical Journal, 2023, 27(7):1459-1465. 
8. Fei Y, Fei R, Zhang J, et al. Systematic Evaluation of Efficacy and Safety of Acupuncture Treatment for 
Patients with Atrial Fibrillation[J]. Open Access Maced J Med Sci, 2019, 7(3):461-466. 
9. Mont L, Bisbal F, Hernández-Madrid A, et al. Catheter ablation vs. antiarrhythmic drug treatment of 
persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur Heart J 2014; 
35(8): 501-7. 
10. Huang H, Liu Y, Shuai W, et al. Atrial tachyarrhythmia prevention by Shensong Yangxin after catheter 
ablation for persistent atrial fibrillation: the SS-AFRF trial. Eur Heart J 2024; 45(40): 4305-14.