Effect of Intermittent Urethral Catheter Clamping Combined With Active Urination Training (ICCAUT) Strategy on Postoperative Urinary Dysfunction After Radical Rectal Cancer Surgery: a Single-Center Randomized Controlled Trial (ICCAUT-1)
Phase: NA
Conditions: Urinary Dysfunction, Rectal Cancer, Urinary Catheterization, Urinary Retention Postoperative
Sponsor: The First Hospital of Jilin University

 
 
 
 
 
The effect of intermittent catheter clamping combined with 
active urination training (ICCAUT) on urinary dysfunction 
after radical resection of rectal cancer: a single-center 
randomized controlled trial 
 
Clinical Study Protocol 
 
 
 
Principal Investigator: Yuchen Guo，Tingting He 
Signature:                ，                
Department: Gastrocolorectal Surgery, General Surgery 
 
 
 
 
 
Center
Institution: First Hospital of Jilin University
Address: No.1 Xinmin Street, Changchun, China 
Email: guoyuchen8688@jlu.edu.cn
Phone Number: +8613630598312 
 
 
 
 
 

2
Content
Clinical Study Protocol Version 1.1.1————————————3
Clinical Study Protocol Version 2.0—————————————44
Amendment Summary——————————————————92

 
1/ 41 
Version 
1.1.1
 
 
21 February 2024 
The effect of intermittent catheter clamping combined with active urination 
training (ICCAUT) on urinary dysfunction after radical resection of rectal 
cancer: a single-center randomized controlled trial 
 
 
 
 
 
Principal Investigator: Yuchen Guo，Tingting He 
Department: Gastrocolorectal Surgery, General Surgery Center 
Version number：V 1.1.1 
Version date：February 21, 2024 
 
 
 
 

 
2/ 41 
Version 
1.1.1
 
 
21 February 2024 
Content 
1. Background and Rationale ........................................................................................................... 4 
2. Research Objectives and Endpoints ............................................................................................. 6 
2.1 Objective ............................................................................................................................ 6 
2.2 Study Endpoint ................................................................................................................... 7 
2.2.1 Primary Study Endpoint and Definition .................................................................. 7 
2.2.2 Secondary study endpoints and definitions. ............................................................. 7 
2.2.3 Other indicators and definitions. .............................................................................. 8 
3.Study design. ................................................................................................................................. 9 
3.1 Overall study design. .......................................................................................................... 9 
3.2 Study duration. ................................................................................................................... 9 
3.3 Trial flowchart .................................................................................................................... 9 
4. Population. .................................................................................................................................. 10 
4.1 Inclusion criteria ............................................................................................................... 10 
4.2 Exclusion criteria .............................................................................................................. 11 
4.3 Withdrawal criteria. .......................................................................................................... 11 
5. Study treatment groups. .............................................................................................................. 12 
5.1 Randomization and group assignment. ............................................................................. 13 
5.1.1 Methods for Generating Random Sequences ......................................................... 13 
5.1.2 Randomization concealment. ................................................................................. 13 
5.2 Blinding and Unblinding. ................................................................................................. 13 
6. Study procedure .......................................................................................................................... 14 
6.1 Study treatment period. .................................................................................................... 14 
6.1.1 Patient recruitment and randomization. ................................................................. 14 
6.1.2 Intervention ............................................................................................................ 15 
6.1.3 Discharge and follow-up. ....................................................................................... 16 
6.2 Concomitant treatment, follow-up .................................................................................... 18 
6.3 Patient compliance and withdrawal .................................................................................. 18 
6.4 Protocol deviations ........................................................................................................... 19 
7.Evaluation .................................................................................................................................... 19 
7.1 Efficacy evaluation ........................................................................................................... 19 
7.2 Safety evaluation .............................................................................................................. 19 
7.2.1 Baseline vital signs and symptoms ........................................................................ 19 
7.2.2 Laboratory examinations ....................................................................................... 20 
7.2.3 Physical examination and vital signs ..................................................................... 20 
8. Adverse event reporting .............................................................................................................. 20 
8.1 Adverse events .................................................................................................................. 20 
8.2 Definition of adverse events ............................................................................................. 21 
8.3 Abnormal test results. ....................................................................................................... 21 
8.4 Serious adverse events ...................................................................................................... 21 
8.5 Severity assessment .......................................................................................................... 22 
8.6 Causality assessment ........................................................................................................ 22 
9. Data processing and storage ....................................................................................................... 22 
10. Quality management ................................................................................................................. 22 

 
3/ 41 
Version 
1.1.1
 
 
21 February 2024 
11. Statistical analysis .................................................................................................................... 25 
11.1 Sample size determination .............................................................................................. 25 
11.2 Analysis population ........................................................................................................ 25 
11.2.1 Full analysis set .................................................................................................... 25 
11.2.2 Per-protocol analysis set ...................................................................................... 26 
11.2.3 As-treated analysis set .......................................................................................... 27 
11.3 Efficacy analysis and statistical methods ........................................................................ 27 
11.3.1 Analysis of the primary endpoint ......................................................................... 27 
11.3.2 Analysis of secondary endpoints .......................................................................... 27 
11.3.3 Subgroup analysis ................................................................................................ 27 
11.4 Interim analysis ............................................................................................................... 28 
11.5 Final analysis .................................................................................................................. 28 
11.6 Data Monitoring Committee ........................................................................................... 28 
12. Data collection and management .............................................................................................. 29 
12.1 Case Report Form/Electronic Data Recording ............................................................... 29 
12.2 Data management ........................................................................................................... 30 
13. Ethics and Morality .................................................................................................................. 31 
13.1 Ethics committee ............................................................................................................ 31 
13.2 Patient information and informed consent ...................................................................... 31 
14. Definition of study completion ................................................................................................. 32 
15. Trial organizational structure .................................................................................................... 32 
17. Insurance and compensation. .................................................................................................... 33 
18. Publication statement ............................................................................................................... 33 
19.References ................................................................................................................................. 33 
Appendix 1: IPSS Score ................................................................................................................. 36 
Appendix 2: ICIQ-SF Score ........................................................................................................... 38 
Appendix 3: CRBD Grading Assessment ...................................................................................... 39 
Appendix 4: Bladder Training Quality Self-Assessment Form ...................................................... 40 
Appendix 5: Postoperative Complications Clavien-Dindo System Grading. ................................. 41 
 
 
 
 

 
4/ 41 
Version 
1.1.1
 
 
21 February 2024 
1. Background and Rationale 
Gastrointestinal surgery usually requires the placement of a urinary catheter 
during the operation, which is removed after the surgery. For upper gastrointestinal 
surgery, since there is no surgical manipulation of the pelvic and abdominal organs, 
the catheter is usually removed within 2 days after the operation, and urinary retention 
rarely occurs. However, in rectal surgery, which is performed in the pelvic cavity, the 
resection requires the ligation at the root of the inferior mesenteric artery to achieve 
the third station lymph node dissection. During this process, there is a possibility of 
damaging the upper hypogastric plexus and the pelvic nerve plexus. Damage to these 
nerves, along with other potential perioperative factors, can lead to urinary retention 
in patients after rectal surgery, resulting in a significantly increased rate of secondary 
catheterization. Therefore, reducing postoperative urinary retention and the rate of 
secondary catheterization is one of the clinical issues that need to be addressed. 
Bladder training is a method commonly used by surgeons in clinical practice. In 
a clinical study conducted by Williamson in 1982, it was indicated that intermittently 
clamping the catheter before catheter removal may shorten the time required for 
patients to regain bladder function(1).In this procedure, the patient's urinary catheter 
is first clamped.  After clamping for three hours, the catheter is released to allow the 
urine in the bladder to be drained through the catheter.  This cycle is repeated 
multiple times.  It is widely applied across various departments in clinical settings.  
Current research has confirmed that bladder training can be used as a treatment 
method for overactive bladder syndrome, which can reduce the frequency of urination 
and alleviate symptoms of urinary frequency and urgency(2,3).For patients with 
urinary incontinence, bladder training also has a certain therapeutic effect(4).However, 
the effect of bladder training on reducing urinary retention and secondary 
catheterization rates in patients remains debatable. A recent systematic review 
published in the Cochrane suggests that compared with direct catheter removal, 
bladder training through intermittent urethral catheter clamping may not be sufficient 

 
5/ 41 
Version 
1.1.1
 
 
21 February 2024 
to reduce the rate of secondary catheterization in patients(5).In addition, the procedure 
of bladder training may actually increase the rate of urinary tract infections in 
patients(6).At present, the number of RCT studies on bladder training through 
intermittent urethral catheter clamping is limited, and no advantage has been found 
compared to free-drainage in reducing the rate of secondary catheterization. 
It is worth noting that the quality of  RCT trials on the impact of bladder training on 
post-pelvic surgery urinary retention is inconsistent, with study designs that suffer fro
m inadequate basis for sample size calculation, insufficient sample sizes, and low stati
stical power.Additionally, most of the relevant RCT studies have not been conducted 
in strict accordance with the RCT trial process and have not been registered, casting 
doubt on their quality and credibility, making it difficult to derive reliable clinical 
practice evidence from them(6-9).At present, there is no consensus among clinicians 
regarding this issue. Although current guidelines related to urinary catheter care tend 
to suggest that intermittent clamping of the urinary catheter for bladder function 
training cannot effectively reduce the incidence of urinary retention and may even 
increase the incidence of urinary tract infections in patients. However, since most of 
the existing relevant studies are mainly retrospective studies and lack high-quality 
RCT trials, the recommendations in the published guidelines regarding whether to 
conduct bladder training before removing the urinary catheter are all based on 
low-quality research evidence. In clinical practice, especially for patients after low 
radical resection of rectal cancer many centers still perform intermittent urethral 
catheter clamping for bladder training to reduce the incidence of urinary retention and 
the rate of secondary catheterization. In 2020, Muge et al. also published a comment 
in a top nursing journal, pointing out that the impact of postoperative bladder training 
on urinary retention still requires further research(10).Therefore, high-quality clinical 
studies are needed to explore the effectiveness of bladder training. 
In this study, we plan to conduct intermittent clamping of the urinary catheter for 
patients to explore the impact of this procedure on postoperative urinary dysfunction 
after radical resection of rectal cancer. Unlike previous studies, on the basis of 
intermittent clamping of the urinary catheter, we have combined active urination 

 
6/ 41 
Version 
1.1.1
 
 
21 February 2024 
training, which means instructing patients to perform active urination movements 
during the intervals when the catheter is opened, to assist in the emptying of urine 
from the bladder. In recent years, studies have shown that active urination training to 
calculate the efficiency of urination can effectively predict the occurrence of urinary 
retention in patients(11,12).However, there are no studies on the impact of active 
urination training on urinary retention. Theoretically, intermittent catheter clamping 
combined with active urination training can simulate the normal micturition process 
of patients. In addition, studies have shown that active urination training can alleviate 
catheter-related pain in patients(13).Therefore, in this study, we combined intermittent 
urethral catheter clamping training with active urination training. We named this 
urinary catheter management strategy the ICCAUT（intermittent catheterization clamp 
combined with active urination training） management strategy. Currently, there are 
no registered RCT studies on how ICCAUT management strategies affect the 
postoperative urinary function of patients after radical resection of rectal cancer. 
Therefore, this study aims to conduct a prospective randomized controlled trial. It will 
explore whether the ICCAUT management strategy, compared with the free-drainage 
strategy, can affect postoperative urinary dysfunction in patients after proctectomy, 
aiming to provide high-level evidence for clinical practice. 
2. Research Objectives and Endpoints 
2.1 Objective 
Primary Objective 
This study investigated the effects of intermittent catheter clamping combined 
with active urination training (ICCAUT) on postoperative urinary dysfunction in 
patients after proctectomy.  
Secondary Objective 
To explore whether bladder training will increase the risk of postoperative 
urinary tract infections in patients after radical resection of rectal cancer. 

 
7/ 41 
Version 
1.1.1
 
 
21 February 2024 
2.2 Study Endpoint 
2.2.1 Primary Study Endpoint and Definition 
The primary endpoint of the study is urinary dysfunction in patients within 7 
days after catheter removal. In this study, urinary dysfunction was defined as 
incomplete bladder emptying after the first voiding following catheter removal or an 
inability to urinate requiring a second catheterization. 
Incomplete bladder emptying was characterized by a postvoid residual urine 
volume (PRUV) exceeding 100 mL (14–18).The residual urine volume in the bladder 
after the first urination will be estimated immediately following the first urination 
using bladder ultrasound. The calculation formula is: Bladder urine volume = 
Anteroposterior diameter * Vertical diameter * Transverse diameter * 0.52. The 
bladder ultrasound is performed by a fixed radiologist from the ultrasound imaging 
department, who is exclusively assigned to our department. 
The criteria for determining whether secondary catheterization is needed due to 
difficulty in urination are as follows:1)The patient is unable to urinate within 10 hours 
after catheter removal, and percussion of the bladder upper border indicates that it is 
located above the pubic bone, with an estimated residual urine volume in the bladder 
greater than 200 ml using bedside bladder ultrasound;2)Although the patient is able to 
urinate after catheter removal, they still feel lower abdominal distension after multiple 
attempts to urinate, and percussion by the physician indicates that the bladder upper 
border is located above the pubic bone, with an estimated residual urine volume in the 
bladder greater than 200 ml using bedside bladder ultrasound. 
In the assessment of the primary endpoint, if a patient undergoes secondary 
catheterization but does not meet the criteria for withdrawal, and if the urine volume 
drained after secondary catheterization is less than 100 ml, such patients will not be 
defined as having urinary dysfunction. 
2.2.2 Secondary study endpoints and definitions. 

 
8/ 41 
Version 
1.1.1
 
 
21 February 2024 
Secondary endpoints of this study include: 1) Catheter-associated urinary tract 
infection status; 2) Time to first urination after catheter removal; 3) Grading 
assessment of catheter-related bladder discomfort (CRBD); 4) Post-catheter removal 
urinary function evaluation (using ICIQ-SF and IPSS scores); 5) Postoperative 
complications within 30 days (incidence of complications, types of complications, and 
grading of complications). 
2.2.3 Other indicators and definitions. 
Urinary tract infection is defined as an inflammatory response of the urinary 
epithelium to bacterial invasion. The diagnosis requires both of the following criteria 
to be met: 1) Urinalysis indicates a bacterial count above the normal upper limit, and 
2) Positive urine culture. The time to first urination after catheter removal is defined 
as the time from the removal of the catheter to the patient's spontaneous urination, 
measured in hours. The time from the second catheterization to the removal of the 
urinary catheter is defined as the time interval from the first removal of the urinary 
catheter to the completion of catheter insertion by the nurse or suprapubic puncture by 
the ultrasound doctor after the clinician determines that the patient requires a second 
catheterization. 
Complications within 30 days after surgery are assessed according to the 
Clavien-Dindo classification, and complications of grade II and above are recorded 
and analyzed. These include, but are not limited to, intraperitoneal bleeding, 
gastrointestinal bleeding, anastomotic leak, chylous fistula, surgical site infection 
(intra-abdominal infection and incisional infection), intestinal obstruction, 
postoperative diarrhea, pulmonary infection, urinary tract infection, cardiovascular 
accident, cerebrovascular accident, and thrombotic diseases. 

 
9/ 41 
Version 
1.1.1
 
 
21 February 2024 
3.Study design. 
3.1 Overall study design. 
Single-center, prospective, two-arm, parallel-group randomized controlled study. 
3.2 Study duration. 
This study plans to complete patient enrollment within one year. The 
postoperative follow-up period for patients is one month. The entire study, including 
the establishment of the study, patient recruitment, patient follow-up, and data 
analysis, is expected to last for two years. We will conduct the primary endpoint 
analysis after all patients have completed their first postoperative month follow-up. 
The study will begin in February 2024 at the First Hospital of Jilin University. 
3.3 Trial flowchart 
 
As shown in Figure 1. 

 
10/ 41 
Version 
1.1.1
 
 
21 February 2024 
 
Figure 1.Trial flowchart 
4. Population. 
4.1 Inclusion criteria  
1) Patients with a confirmed preoperative diagnosis of rectal cancer. 
2) Patients with tumors located below the rectosigmoid junction, as determined 
by preoperative computed tomography (CT) or rectal magnetic resonance imaging 

 
11/ 41 
Version 
1.1.1
 
 
21 February 2024 
(MRI). 
3) Patients undergoing laparoscopic or robotic-assisted low anterior resection or 
abdominoperineal resection for rectal cancer. 
4.2 Exclusion criteria 
1) History of abdominal surgery involving the rectum, sigmoid colon, left 
hemicolectomy, bladder resection or partial resection, prostate surgery, or 
hysterectomy. 
2) History of urethral injury, cranial surgery, spinal surgery, stroke with limb 
dysfunction, or Parkinson's disease. 
3) Inability to urinate through the urethra preoperatively due to various reasons 
(e.g., ureteral puncture or ureterostomy). 
4) Presence of urinary tract infection preoperatively. 
5) Previously diagnosed with bladder overactivity syndrome, urinary retention or 
voiding dysfunction, or diabetic bladder disease. 
6) Concomitant resection of other pelvic organs was performed during surgery, 
including the bladder, prostate, uterus, cervix, and vagina, except for simple adnexal 
resection. 
7) Lateral lymph node dissection for rectal cancer. 
8) Injury to the ureter, bladder, or urethra during the perioperative period. 
9) Preoperative renal dysfunction (serum creatinine level >133 μmol/L). 
10) Emergency surgery. 
11) Male patients with preoperative benign prostatic hyperplasia receive 
medication treatment. 
12) Patients with a ureteral stent or ureteral stricture, or bilateral hydronephrosis. 
13) Conversion to open surgery. 
4.3 Withdrawal criteria. 
After randomization, patients will be withdrawn from the trial if any of the 

 
12/ 41 
Version 
1.1.1
 
 
21 February 2024 
following situations occur: 
1) Inability to remove the urinary catheter within 5 days postoperatively due to 
various reasons (e.g., impaired consciousness, transfer to the intensive care unit (ICU), 
Sequential Organ Failure Assessment (SOFA) score ≥2, etc.). 
2) Secondary catheterization was performed for reasons other than urinary 
retention (e.g., secondary surgery, shock, rectal bladder leakage, ureteral leakage, or 
urethral injury). 
3) Patient requests to withdraw from the study at any time during the entire study 
process. 
4) Selective α1-adrenergic receptor blocker is used during the first catheterization 
of the patient due to medical necessity. 
5. Study treatment groups. 
ICCAUT group（Experimental group）：Patients underwent laparoscopic or 
robotic rectal cancer TME surgery, and bladder function exercises were initiated 
through intermittent catheter clamping at 9:00 am on the first postoperative day, with 
the urinary catheter removed at 9:00 am on the second postoperative day. 
Free-drainage group（Control group.）：Patients underwent laparoscopic or robotic 
rectal cancer TME surgery, with the urinary catheter kept open postoperatively, and it 
was removed at 9:00 am on the second postoperative day. 
Physicians need to determine whether to remove the urinary catheter according 
to the planned date based on a comprehensive assessment of the patient's 
consciousness, postoperative renal function, circulatory status, and other factors. 
Using the Sequential Organ Failure Assessment (SOFA) score as a reference, if the 
patient's SOFA score is less than 2, the catheter will be removed as planned during the 
day on the second postoperative day. If the SOFA score is 2 or higher, the duration of 
catheter placement should be extended. If the catheter still cannot be removed by the 
fifth day due to a SOFA score of 2 or higher, the patient will be excluded according to 

 
13/ 41 
Version 
1.1.1
 
 
21 February 2024 
the withdrawal criteria. The specific situation still requires a comprehensive judgment 
by the physician. If the catheter is not removed as planned, the reason must be stated 
in the CRF form. Additionally, if a patient is suspected of having a urinary tract 
infection during catheter training, the clinical physician may decide to stop the 
catheter exercise. 
5.1 Randomization and group assignment. 
5.1.1 Methods for Generating Random Sequences 
Patients who meet the inclusion criteria will be randomly assigned to either the 
bladder training group or the direct removal group. Stratified randomization will be 
performed based on the following three factors, with randomization information 
generated using R language on a computer. The stratification factors are: 1) Gender; 2) 
Whether undergoing abdominoperineal resection (APR). The randomization ratio 
between the ICCAUT group and the Free-drainage group is 1:1. The randomly 
assigned time is on the day when the patient returns to the ward after the operation. 
The randomization will be distributed to the assigned nurse via an envelope, and the 
bladder training will be conducted by the assigned nurse. 
5.1.2 Randomization concealment. 
After randomization, the group assignment information will be printed on a slip 
of paper and placed into an opaque envelope. Before 8:00 am on the second 
postoperative day, the envelope containing the group assignment information will be 
given to the assigned nurse, who will conduct the catheter training. 
5.2 Blinding and Unblinding. 
This study is blinded to the physician group, the ultrasound imaging physicians 
who assess bladder residual urine volume, and the data analysts. The study group 
requires patients and assigned nurses to keep the patient's group assignment 

 
14/ 41 
Version 
1.1.1
 
 
21 February 2024 
confidential from the assigned physicians and bladder ultrasound physicians. Since 
the clinical operations are performed by the assigned nurses on the patients, this study 
cannot blind the patients and assigned nurses. The time of unblinding is at the time of 
patient discharge, and any premature unblinding will be recorded. Additionally, this 
study is blinded to the data statisticians. 
6. Study procedure 
6.1 Study treatment period. 
As shown in Table 1  
6.1.1 Patient recruitment and randomization. 
1）After admission, patients are initially assessed to determine if they meet the 
inclusion criteria. If they do, urinalysis and urine culture are performed. The patient's 
urinary function is evaluated using the International Prostate Symptom Score (IPSS) 
(Appendix 1) and the International Consultation on Incontinence Questionnaire Short 
Form (ICIQ-SF) (Appendix 2), and baseline data are collected. 
2）Participants will undergo laparoscopic or robotic‑assisted radical resection of 
rectal cancer. For patients with a narrow pelvic cavity or ultra‑low rectal tumors 
scheduled to receive low anterior resection (LAR), either transanal total mesorectal 
excision (TaTME) or the Turnbull‑Cutait pull‑through procedure combined with 
two‑stage hand‑sewn coloanal anastomosis (TCA) will be employed. The second 
stage of the TCA procedure will be performed 2 to 3 weeks following the initial 
operation. All surgeons will be required to perform high ligation of the inferior 
mesenteric artery (IMA) and to preserve Denonvilliers' fascia. The decision to 
perform APR will be based on the patient's tumor stage and the outcome of 
communication between the surgeon and the patient. After surgery, patients are 
reassessed to determine if they still meet the inclusion criteria and are checked against 
each exclusion criterion. If they are not excluded, they are deemed suitable for 

 
15/ 41 
Version 
1.1.1
 
 
21 February 2024 
enrollment. The patient is then informed and asked to sign the informed consent. If 
the patient is informed and agrees to participate, the informed consent form is signed, 
and randomization begins. Baseline data and surgical-related data for the enrolled 
patients are then collected and completed. 
3）Based on stratification factors, randomization is conducted on a computer. 
The randomization information will be delivered to the assigned nurse via an 
envelope before 8:00 am on the day following surgery. The nurse will then perform 
the catheter operation according to the group assignment indicated in the envelope. 
6.1.2 Intervention 
On the day following surgery (postoperative day 1) at 9:00 am, the nurse will 
perform the corresponding intervention operations for patients in both groups based 
on the group assignment indicated in the randomization envelope. Before the 
intervention, both groups of patients must complete the CRBD (Catheter-Related 
Bladder Discomfort) grading assessment by the assigned nurse (Appendix 3). During 
the patient's first catheterization, the use of selective α1-adrenergic receptor blockers 
(such as tamsulosin) is not permitted. 
1）The ICCAUT strategy included intermittent urethral catheter clamping and 
active urination training. In the ICCAUT group, intermittent catheter clamping was 
initiated at 9:00 am on the frst postoperative day. In each cycle, the catheter was 
clamped for 3 h, followed by a 5-min release. The next cycle began as soon as the 
previous cycle had been completed. Catheter training concluded at 10:00 pm on the 
frst postoperative day, and the catheter was left open during the night. The urinary 
catheter was removed on the second postoperative day, and the training did not stop 
until the catheter had been removed. During the training period, if the patient 
experienced a strong urge to urinate before the 3-h clamping time was over, the 
clamping could be released in advance for 5 min, allowing the patient to proceed to 
the next cycle of bladder training. Each time the catheter was released, the patients 
were encouraged to actively initiate urination to facilitate complete bladder emptying. 
We refer to this catheter management strategy, which involves intermittent clamping 

 
16/ 41 
Version 
1.1.1
 
 
21 February 2024 
of the catheter and active urination during the release periods, as the ICCAUT 
management strategy. 
2）For patients in the free-draining group, no intervention was performed using a 
catheter during this period. The urinary catheter was removed at 9:00 am on the 
second postoperative day. 
3）Before the urinary catheter is removed on the second day, both groups of 
patients must complete the CRBD (Catheter-Related Bladder Discomfort) grading 
assessment again by the assigned nurse (Appendix 3), and urine samples must be 
collected for urinalysis and urine culture. Additionally, patients in the ICCAUT group 
must scan a code to fill out the Bladder Training Quality Self-Assessment Form 
(Appendix 4) before the catheter is first removed. After the catheter is removed, the 
time from the first catheter removal to the first urination, as well as the volume of the 
first urination, should be recorded for both groups of patients. 
4）Immediately after the first urination, a bladder ultrasound must be performed 
to assess the residual urine volume in the bladder. The bladder ultrasound is 
conducted by a fixed radiologist from the ultrasound imaging department, who is 
exclusively assigned to our department and is located in the same therapeutic area as 
the patient. After the urinary catheter is removed, the patient must be observed and the 
situation of any secondary catheterization must be recorded. The observation period is 
the following 7 days after first urinary catheter removal. For patients who undergo 
secondary catheterization, the time from the first catheter removal to the secondary 
catheterization, the volume of urine drained after secondary catheterization, the 
method of secondary catheterization, and the reason for secondary catheterization 
must be recorded. 
5）Record the IPSS score and ICIQ-SF score of the patient on the day following 
the first catheter removal (excluding patients who underwent secondary 
catheterization). Record complications within 30 days after surgery and their 
Clavien-Dindo classification (Appendix 5). 
6.1.3 Discharge and follow-up. 

 
17/ 41 
Version 
1.1.1
 
 
21 February 2024 
    After discharge, when the patient returns for a follow-up visit one month after 
surgery, the physician must collect information on complications and their grading 
within the first postoperative month, and conduct an assessment using the one-month 
postoperative urinary function score form. 
Table 1: Study Enrollment, Intervention, and Outcome Assessment Form 
 
 
Study phase 
 
Recruit
ment 
Surgery 
and 
randomiz
ation 
 
Post-randomization 
 
Time point 
Item 
Pre-ran
domizat
ion 
0 
Befor
e 
cathet
er 
remov
al 
After 
cathet
er 
remov
al 
One month 
postoperatively 
Enrollment： 
 
 
 
 
 
 
       
Screen suitable population 
X 
 
 
 
 
 
      Informed consent 
X 
 
 
 
 
 
      Baseline and 
surgery-related data 
collection 
X 
X 
 
 
 
 
     Randomization 
 
X 
 
 
 
 
Intervention： 
 
 
 
 
 
 
      ICCAUT group 
 
 
X 
 
 
 
      Free-drainage 
group 
 
 
X 
 
 
 
Assessment: 
 
 
 
 
 
 
Bladder residual urine 
volume and secondary 
catheterization record 
 
 
 
X 
 
 
      Record of 
information after catheter 
removal 
 
 
 
X 
 
 
      Catheter-related 
bladder discomfort 
(CRBD) grading 
assessment 
 
 
X 
 
 
 
     Bladder training 
self-assessment form 
 
 
X 
 
 
 

 
18/ 41 
Version 
1.1.1
 
 
21 February 2024 
      Urinalysis and 
urine culture 
X 
 
X 
 
 
      Urinary function 
assessment 
X 
 
 
X 
X 
      Postoperative 
complications and grading 
 
 
X 
X 
X 
6.2 Concomitant treatment, follow-up 
The total follow-up time for postoperative patients is one month. The follow-up 
content includes postoperative complications within 30 days, as well as the IPSS and 
ICIQ-SF scores at one month postoperatively. 
The follow-up within the first 30 days after surgery is conducted through 
in-hospital observation, outpatient visits, phone calls, or questionnaires. 
Complications related to the surgery and their grading, as well as the solutions, are 
recorded during this period 
The postoperative chemotherapy regimen for patients will be based on the 
NCCN 2023 Rectal Cancer Treatment Guidelines, which will guide the appropriate 
chemotherapy or systemic treatment. 
6.3 Patient compliance and withdrawal 
If patients refuse the randomly assigned urinary catheter management method at 
any time during the indwelling of the urinary catheter after random grouping and 
request that the operation be carried out according to another urinary catheter 
management method, their wishes shall be followed and they will be included in the 
modified intent-to-treat (mITT) analysis set. In the mITT analysis, the primary 
outcomes of patients will still be analyzed according to the situation of random 
grouping rather than the actual treatment received.After randomization, patients may 
withdraw from the trial at any time. If at any point during the entire study, a patient 
requests to withdraw, the principal investigator of the research center will 
communicate with the patient to avoid disrupting the balance of randomization due to 
withdrawal. If the patient still insists on withdrawing, their preference will be 
respected, and the patient will be excluded from the trial. The clinical information 

 
19/ 41 
Version 
1.1.1
 
 
21 February 2024 
related to this patient will not be included in any data analysis related to this trial. 
6.4 Protocol deviations 
 
Researchers participating in the experiment will follow the experimental 
requirements for the corresponding operations and data recording. Any events that 
deviate from the original trial protocol must be recorded with the time of occurrence 
and specific reasons, and any deviations from the trial protocol must be explained. 
7.Evaluation 
7.1 Efficacy evaluation 
The efficacy evaluation methods for different interventions include, but are not 
limited to: postoperative assessment of symptoms and signs, postoperative ultrasound 
assessment of the urinary system, postoperative evaluation of urination-related 
parameters, postoperative urinalysis and urine culture assessment, and postoperative 
surveys on urination function-related questionnaires. 
7.2 Safety evaluation 
7.2.1 Baseline vital signs and symptoms 
When conducting a safety assessment, it is first necessary to understand the 
baseline vital signs and symptoms of the test subjects. This includes measuring their 
body temperature, pulse, respiratory rate, and blood pressure, while noting any 
specific symptoms such as dizziness, nausea, vomiting, etc. Preoperative 
hematological examinations and imaging studies should be completed, along with 
preoperative urinalysis, urine culture, and preoperative voiding function questionnaire 
assessments. Additionally, the patient's medical history must be clarified and 
cross-checked against the trial's inclusion and exclusion criteria one by one to ensure 

 
20/ 41 
Version 
1.1.1
 
 
21 February 2024 
that the patient population has no surgical contraindications and fully meets the 
enrollment criteria. These baseline data will serve as reference indicators for the 
assessment. 
7.2.2 Laboratory examinations 
The continuity indicators describe the measured values of each research subject 
after surgery and the change values relative to the preoperative baseline. The 
laboratory indicators are divided into low, normal, and high according to the normal 
value range. Describe the situations where the values change from normal or high at 
baseline to low after baseline, and where the values change from normal or low at 
baseline to high after baseline. The low or high values after baseline are calculated 
using the minimum or maximum observed value after baseline. Doctors will evaluate 
these abnormal indicators to determine whether their abnormalities have clinical 
significance. Describe the proportion of "abnormal and clinically significant" among 
the subjects with abnormal changes. 
7.2.3 Physical examination and vital signs 
Physical Examination: General examination, head examination, neck 
examination, thorax and lung examination, heart and vascular examination, abdominal 
examination, spine and limbs examination, and neurological examination. Vital signs 
include routine blood pressure, heart rate, body temperature, etc. Statistical 
descriptions are provided for the measurement values of physical examination, vital 
signs, and weight before and after treatment relative to the baseline. Abnormal vital 
signs or those exceeding the normal value range are described. 
8. Adverse event reporting 
8.1 Adverse events 
Adverse events in the study include complications and death events within 30 

 
21/ 41 
Version 
1.1.1
 
 
21 February 2024 
days after surgery. All adverse events reported spontaneously by the subjects or 
observed by the staff will be recorded in the database and promptly reported to the 
trial steering committee. 
8.2 Definition of adverse events 
An adverse event is defined as any untoward experience occurring in a subject 
during the study, regardless of whether it is considered to be related to catheter 
clamping. All adverse events reported spontaneously by the trial subject or observed 
by the investigator or their staff will be recorded. 
8.3 Abnormal test results. 
Abnormal test results should be evaluated to determine whether they should be 
reported as adverse events based on the following criteria for objective test values: 1) 
Test results are accompanied by symptoms; 2) Test results require medical or surgical 
intervention; 3) The investigator considers the test result to be an adverse event. 
If none of the above criteria are met, merely repeating an abnormal test does not 
constitute an adverse event. Test results judged by the investigator to be erroneous do 
not need to be reported as adverse events. 
8.4 Serious adverse events 
Serious adverse events include any of the following adverse medical events: 1) 
Events or effects leading to death; 2) Life-threatening events; 3) Events requiring 
hospitalization or prolonging the hospital stay of an inpatient; 4) Events resulting in 
persistent or significant disability or incapacity. Upon learning of a serious adverse 
event that is life-threatening or leads to death, it must be reported within 7 days. Other 
serious adverse events must be reported within 15 days. All adverse events are 
followed up immediately after they occur, until the event stabilizes or improves. 
Depending on the specific situation, follow-up may require additional tests or medical 

 
22/ 41 
Version 
1.1.1
 
 
21 February 2024 
procedures, or further referral. 
8.5 Severity assessment 
The severity of adverse events will be assessed using the Clavien-Dindo 
classification of complications. 
8.6 Causality assessment 
The causality of adverse events with respect to the intervention will be 
subjectively assessed by the investigator. 
9. Data processing and storage 
Clinical research data will be recorded through the perioperative eCRF, including 
perioperative information, pathological data, and follow-up information. To protect 
patient privacy, patient identification numbers will not be disclosed to data analysts. 
All patients will be coded and identified using random numbers. These random 
numbers do not include patient initials or date of birth. Members of the trial steering 
committee will have a decoding list that specifies the random numbers of patients in 
the database and their identification numbers. 
All patients who meet the inclusion criteria will be registered, including those 
who refuse randomization, those excluded due to exclusion criteria, and those who are 
withdrawn after randomization due to withdrawal criteria. Reasons for exclusion and 
withdrawal will be recorded. 
10. Quality management 
The key to the quality control of the trial lies in: 
（1）Blinding quality control 
The implementation of blinding in this study may affect the quality of the 

 
23/ 41 
Version 
1.1.1
 
 
21 February 2024 
research, particularly the achievement of the primary endpoint. If the trial is not 
blinded to surgeons, it may influence their judgment on whether the patient needs 
secondary catheterization based on whether bladder training was performed. If the 
ultrasound imaging physicians are not blinded, it may affect their assessment of 
residual urine volume in the bladder based on their knowledge of the patient's 
intervention. Therefore, blinding the randomization information from surgeons and 
ultrasound imaging physicians is one of the key aspects of quality control in this 
experiment. To this end, the study requires patients and nurses to keep the patient's 
group assignment confidential from surgeons and ultrasound imaging physicians. 
Surgeons and ultrasound physicians must also consciously adhere to the principle of 
not inquiring about the patient's group assignment. Any premature unblinding must be 
recorded, including the reason and time of unblinding. 
（2）Interventional method quality control 
The implementation quality of the interventional method is the second key point 
of quality control in this study. To address this, the study implements quality control 
in the following aspects:1) All assigned nurses receive training, which includes 
standardized procedures for clamping and unclamping the urinary catheter, as well as 
the standardized operation for obtaining urine routine and urine culture before catheter 
removal；2) After the patient signs the informed consent and is enrolled, the assigned 
physician is clearly informed not to provide clinical advice on whether to clamp the 
catheter and not to participate in any operations related to bladder training. 
Additionally, the trial management group communicates with the patient that if the 
assigned physician suggests bladder training, the patient should promptly report to the 
assigned nurse and the trial steering committee. The trial steering committee will then 
communicate again with the assigned physician and emphasize the quality control 
points of the trial；3) The start of training is uniformly set for 9:00 am on the first 
postoperative day, and the removal of the catheter is uniformly set for 9:00 am the 
next day. It is not recommended to advance or delay the catheter removal time. Any 
orders to advance or delay the catheter removal must be communicated to the trial 
steering committee members before execution, with reasons provided. If the trial 

 
24/ 41 
Version 
1.1.1
 
 
21 February 2024 
steering committee deems the reason valid, the order to advance or delay the catheter 
removal is allowed to be executed；4) Nurses need to educate and guide enrolled 
patients to ensure that patients in the bladder training group actively perform forceful 
urination during each period of unclamping to assist in urine discharge；5) Patients in 
the bladder training group, if unable to persist in reaching the specified catheter 
clamping time (less than 3 hours of catheter clamping before feeling the urge to 
urinate), may end a training cycle early, open the catheter for 5 minutes, and then start 
the next clamping training cycle；6) Before catheter removal, patients in the bladder 
training group must complete the Bladder Training Quality Self-Assessment Form；7) 
During the first catheterization, selective α1-adrenergic receptor blockers (such as 
tamsulosin) should not be used. If medically necessary, the patient must withdraw 
from the trial. 
（3）Endpoint quality control 
Our project team requires all levels of physicians in our department to strictly 
follow the bladder residual urine assessment method and the criteria for secondary 
catheterization as stipulated in the project research plan to calculate bladder residual 
urine and decide whether to perform secondary catheterization. To reduce bias in the 
measurement of bladder residual urine, this study implements quality control in the 
following two aspects: 1) A fixed radiologist is responsible for assessing bladder 
residual urine, and this physician has specialized in abdominal digestive and urinary 
system ultrasound examinations for over 10 years; 2) The ultrasound diagnosis 
location is set in the same therapeutic area as the patient, ensuring that patients can 
undergo immediate ultrasound examination after the first urination following catheter 
removal, avoiding the impact on the judgment of residual urine due to a long interval 
between urination and ultrasound examination. 
To ensure the collection of primary and secondary endpoints, this study will 
appoint a supervisory nurse to serve as the Clinical Research Coordinator (CRC). The 
CRC will daily verify the patient's enrollment, withdrawal, achievement of primary 
endpoints, and measurement of secondary endpoints. They will remind physicians to 
perform relevant medical orders, nurses to execute medical orders and collect data, 

 
25/ 41 
Version 
1.1.1
 
 
21 February 2024 
and patients to fill out the required questionnaires and self-assessment forms in a 
timely manner. Additionally, the study will arrange for two graduate students to work 
with the CRC to promptly enter data into the Electronic Case Report Form (eCRF) 
and the database (Epidata). 
（4）Regular education for healthcare personnel involved in the study. 
The research group of this project will conduct regular education for all 
physicians and nurses involved in the study on a monthly basis. The main content of 
the education includes the three quality control aspects mentioned above: blinding 
quality control, interventional method quality control, and endpoint quality control. 
This ensures that physicians and nurses can strictly follow the quality control 
requirements of the study for related operations and ensures the quality of the 
intervention operations performed by nurses on enrolled patients. 
11. Statistical analysis 
11.1 Sample size determination 
The sample size is calculated based on a differential test, with urinary dysfunction 
as the primary endpoint. Based on our preliminary research results, we estimate the 
incidence of urinary dysfunction in the bladder training group is 44.7%, and in the 
direct removal group, it is 59.3%. Patients are randomly assigned to the two groups in 
a 1:1 ratio. With a two-sided significance level α of 0.05 and a power (1-β) of 80%, 
the sample size was calculated using PASS 15 software. Each group, the ICCAUT 
group and the free-drainage group, requires 180 cases. Assuming a dropout rate of 
10%, each group requires 200 cases. Therefore, this trial needs a total of 400 cases. 
11.2 Analysis population 
11.2.1 Full analysis set 
The comparative analysis of the primary outcomes will be conducted on the basis 

 
26/ 41 
Version 
1.1.1
 
 
21 February 2024 
of the "modified intention-to-treat (mITT)". The mITT analysis will include patients 
who did not follow the randomly assigned measures but were not excluded according 
to the withdrawal criteria. In this study, if a patient meets the withdrawal criteria after 
randomization, this patient will be excluded, and the relevant data of this patient will 
not appear in the statistical analysis including the mITT analysis. In the mITT analysis, 
for patients randomly assigned to the bladder training group, if the catheter is directly 
removed without undergoing training at the end, the analysis will still be carried out 
according to the bladder training group; for patients randomly assigned to the direct 
removal group, if they receive bladder training at the end, the analysis will still be 
carried out according to the direct removal group. In addition, if a patient undergoes 
secondary catheterization, does not meet the withdrawal criteria, but the urine volume 
drawn after secondary catheterization is less than 100ml. We will not consider that 
this secondary catheterization is caused by bladder emptying disorder. In the analysis, 
we will not classify such patients as having urinary dysfunction. In the mITT analysis, 
we will still include these patients in the analysis, but instead of classifying them as 
end-point events (positive events), we will analyze them as negative events. 
Specific possible reasons for not following the randomization procedure include: 
1) The patient's urine becomes cloudy during the postoperative catheterization period, 
and the physician suspects a urinary tract infection, thus not recommending bladder 
training; 2) The patient cannot tolerate catheter clamping and refuses bladder training; 
3) The patient refuses to follow the assigned procedure; 4) The nurse fails to perform 
the operation according to the assigned method; 5) The catheter is not removed on the 
second postoperative day, either earlier or later (but not beyond the fifth postoperative 
day). The study needs to record the specific reasons for not following the planned 
procedure. 
11.2.2 Per-protocol analysis set 
In the per-protocol analysis set (PPA), only cases that strictly follow the 
randomization and the assigned treatment plan will be included in the analysis. 
Patients who do not receive treatment according to the assigned randomization plan 

 
27/ 41 
Version 
1.1.1
 
 
21 February 2024 
will be excluded from the PPA. Excluded patients include those who did not have the 
catheter removed on the second postoperative day, as well as those whose bladder 
training was not conducted strictly according to plan. 
11.2.3 As-treated analysis set 
In the as-treated analysis set (ATA), we will analyze patients based on the actual 
treatment they received, rather than the treatment assigned by randomization. In the 
ATA analysis, patients who receive at least one round of bladder training are 
classified as the bladder training group, while those who do not receive training are 
classified as the direct removal group. 
11.3 Efficacy analysis and statistical methods 
11.3.1 Analysis of the primary endpoint 
Categorical variables will be statistically analyzed and described using counts 
(percentages). Without multivariate adjustment, the primary endpoints of the two 
groups will be compared using relative risk (RR) and its 95% confidence interval (95% 
CI) to describe the differences between the groups. Additionally, logistic regression 
will be used to adjust for factors that may affect the rate of secondary catheterization 
(such as the relationship between the lower edge of the tumor and the peritoneal 
reflection, BMI, age, surgery duration, etc.). The adjusted differences between groups 
will be described using odds ratios (OR) and 95% CI. 
11.3.2 Analysis of secondary endpoints 
In the analysis of secondary endpoints, continuous variables will be described 
using mean ± standard deviation or median (interquartile range); categorical variables 
will be described using counts (percentages). We will consider using sensitivity 
analysis to explain the impact of missing data on overall results. 
11.3.3 Subgroup analysis 

 
28/ 41 
Version 
1.1.1
 
 
21 February 2024 
    We will explore differences in the rate of secondary catheterization between the 
two groups in different subgroups through subgroup analysis. Subgroups include Sex 
(male; female), age (≤65 years; >65 years), ASA classification (≤II; ≥III), BMI (≥28 
kg/m²; <28 kg/m²), the relationship between the lower edge of the tumor and the 
peritoneal reflection (above the peritoneal reflection; below the peritoneal reflection), 
Operating time (≤180 mins; >180 mins), neoadjuvant therapy Yes, No), and surgical 
procedures (LAR surgery; APR surgery; TaTME surgery; Bacon surgery; ISR surgery; 
CAA surgery). Logistic regression will be used for univariate and multivariate 
analyses, with effect sizes represented by OR and 95% CI, and subgroup interaction 
P-values will be calculated. Additionally, we will conduct exploratory subgroup 
analyses for some key secondary endpoints, such as the incidence of urinary tract 
infections. 
All hypothesis tests are two-sided with a significance level of 5%. We will 
analyze the results and write the paper after all enrolled patients have completed the 
one-month follow-up. 
11.4 Interim analysis 
This study does not include an interim analysis 
11.5 Final analysis 
 
We will conduct the primary endpoint analysis of the study after all patients have 
completed their first postoperative month follow-up and will publish the relevant 
research findings. 
11.6 Data Monitoring Committee 
This study establishes a Data and Safety Monitoring Board (DSMB), which is 
composed of senior surgeons, ethicists, and statistical analysts. The members of the 
DSMB are independent of this trial and have no competing interests that could 

 
29/ 41 
Version 
1.1.1
 
 
21 February 2024 
influence the trial. The DSMB will receive and review the safety data of this trial. If 
the DSMB believes that the number of adverse events in the trial is biased between 
groups, they will notify the trial steering committee. 
No interim analyses are planned in this study. However, after the study begins, 
the DSMB will assess the study results every six months and may meet earlier for 
assessments. The assessment content includes the recording of primary and secondary 
endpoints, adverse events, and the dropout rate of study samples. Except for the trial 
steering committee, DSMB members must not share confidential information with 
anyone outside the DSMB. 
The interventional methods used in this study (intermittent catheter clamping and 
continuous catheter opening) are common clinical strategies for managing catheters 
after surgical procedures and do not impose additional risks on patients. Therefore, 
this study does not have predefined stopping criteria. However, if the regular 
assessments by the DSMB reveal that the urinary system-related safety indicators due 
to the intervention methods are significantly worse than the current domestic 
standards, the DSMB will submit its recommendations in writing to the trial steering 
committee. This may include requests to modify the trial plan, re-evaluate the quality 
of cases, or even suspend or terminate patient enrollment in the clinical trial. 
12. Data collection and management 
12.1 Case Report Form/Electronic Data Recording 
The Case Report Form (CRF) includes the following primary outcome measures: 
incidence of urinary dysfunction, including bladder residual urine volume after the 
first urination, rate of secondary catheterization, time from catheter removal to 
secondary catheterization (hours), method of secondary catheterization (suprapubic 
puncture/urethral catheterization), reasons for secondary catheterization, and urine 
volume drained after secondary catheterization (ml). Secondary outcome measures 
include: urinary tract infection status (white blood cell count in urine, bacterial 

 
30/ 41 
Version 
1.1.1
 
 
21 February 2024 
content, and positive/negative urine culture before catheter removal), time to first 
urination after catheter removal (hours), bladder residual urine volume after the first 
urination (milliliters), CRBD grading assessment, bladder training quality 
self-assessment form for the bladder training group, postoperative complications 
within 30 days (incidence of complications, types of complications, and grading of 
complications), and urinary function assessment on the second day after catheter 
removal (ICIQ-SF, IPSS score).Other collected baseline indicators include: gender, 
age, underlying diseases and medical history (hypertension, diabetes, cardiovascular 
disease, cerebrovascular disease, history of pelvic surgery), history of benign prostatic 
hyperplasia in males (confirmed by medical history or imaging), preoperative IPSS 
score, preoperative ICIQ-SF score, preoperative radiotherapy and chemotherapy 
status, preoperative urine routine white blood cell count, preoperative urine routine 
bacterial count, preoperative urine culture results, ASA, BMI, preoperative imaging 
assessment results (preferably rectal MRI), including the distance from the lower edge 
of the tumor to the anal margin, the relationship between the lower edge of the tumor 
and the peritoneal reflection (above/below the peritoneal reflection), clinical T staging, 
clinical N staging, MRF status, EMVI status, surgery duration, surgical procedures, 
including low anterior resection (LAR), intersphincteric resection (ISR), 
abdominoperineal resection (APR), transanal TME (TaTME), Bacon surgery, stoma 
status (ileum/colon, single/double), surgical technique (robotic/laparoscopic), and 
postoperative pathological conditions (pathological T staging, pathological N staging, 
CRM, DRM). See the CRF form for details. 
12.2 Data management 
Data collection will be conducted by the CRC, who will verify and collect 
information on patient enrollment, withdrawal, achievement of primary endpoints, 
and measurement of secondary endpoints daily. Two graduate students will serve as 
data entry personnel. The two graduate students and the CRC will jointly collect 
baseline data. Data entry will be performed using a dual-entry method, with one 

 
31/ 41 
Version 
1.1.1
 
 
21 February 2024 
person entering the data and another verifying it. Both paper and electronic versions 
of the CRF will be entered simultaneously. Baseline data will be entered on the day of 
surgery, information related to primary and secondary endpoints will be entered 
within two days of catheter removal, and pathological and other hospitalization 
information must be entered within one week after patient discharge. Complications 
within 30 days after surgery must be entered within 30 days after surgery. To protect 
patient privacy, all patients will be coded and identified using random numbers. These 
random numbers do not include patient initials or date of birth. Investigators will have 
a decoding list that specifies the random numbers of patients in their site's files and 
their patient identification numbers. 
All patients who meet the inclusion criteria will be recorded. If a patient is 
excluded due to exclusion criteria or is withdrawn after randomization due to 
withdrawal criteria, this must be documented in the database. 
13. Ethics and Morality 
13.1 Ethics committee 
Before the study begins, this trial will obtain ethical approval from the ethics 
committee of our hospital. 
13.2 Patient information and informed consent 
Eligible patients should receive personal notification from the treating surgeon 
and be provided with written information related to the trial. Before entering the 
randomization of the study, each patient must provide informed consent in accordance 
with the guidelines of the ethics committee. Patients will have at least 24 hours to 
decide whether to participate in the study and can withdraw from the study at any time 
without reason. 
The informed consent process should be conducted by a physician of the 

 
32/ 41 
Version 
1.1.1
 
 
21 February 2024 
attending level or higher within our group. The information provided to patients 
during informed consent includes:1) A statement that the trial involves research;2) A 
full and fair explanation of the procedures to be followed;3) A full explanation of the 
nature, expected duration, and purpose of the research;4) A description of any risks or 
discomforts that the patient can reasonably expect;5) A description of any benefits 
that can be reasonably expected;6) A statement that patient data will be handled with 
care and confidentiality, and the duration of data retention (15 years);7) A statement 
that patient biological materials will be retained for 15 years;8) A statement about 
voluntary participation and withdrawal, indicating that refusal to participate in the 
trial involves no penalty or loss of benefits to which the patient is otherwise entitled, 
and that the patient may stop participating at any time without penalty or loss of 
benefits, in which case the patient will receive standard care of the same quality. 
14. Definition of study completion 
The study is considered complete when all enrolled patients have completed a 
one-month follow-up. 
15. Trial organizational structure 
This study is conducted at a single medical center—The First Hospital of Jilin 
University. The trial steering committee members include Quan Wang , Haiyan Hu, 
Jianan Sun, Yuchen Guo , and Tingting He . The Data and Safety Monitoring Board 
(DSMB) is composed of senior surgeons, ethicists, and statistical analysts. Each 
member of the DSMB is independent of this trial and has no competing interests that 
could influence the trial. This study has no research funding support. 
16. Confidentiality and data security 
During the study, only data entry personnel and the DSMB are aware of the data 
situation, and others cannot access the database to know specific patient data. DSMB 

 
33/ 41 
Version 
1.1.1
 
 
21 February 2024 
members can be aware of patient allocation and trial-related data. The DSMB will 
discuss the relevant results of the data with the trial steering committee members. 
Except for the trial steering committee, DSMB members must not share confidential 
information with anyone outside the DSMB. 
For decisions and recommendations formed through discussions by the DSMB, 
the DSMB will submit these recommendations in writing to the trial steering 
committee. Additionally, the CRC will also receive these recommendations to be 
discussed at the trial steering committee meeting. The content of the meeting needs to 
be stored and secured by the DSMB members after the meeting, so that it can be 
reviewed in comparison with the next report. 
17. Insurance and compensation. 
All enrolled patients have purchased medical commercial insurance in 
collaboration with our hospital and an insurance company before surgery. The 
insurance will compensate for surgery-related complications and surgery-related 
deaths. 
18. Publication statement 
The data will not be published before the collection of primary outcomes is 
completed. We will conduct the primary endpoint analysis of the study after all 
patients have completed their first postoperative month follow-up and will publish the 
relevant research findings. The order of authors will be arranged from highest to 
lowest based on the number of enrolled cases. 
19.References 
1. 
Williamson ML. Reducing post-catheterization bladder dysfunction by reconditioning. 
Nurs Res. 1982;31(1):28–30.  

 
34/ 41 
Version 
1.1.1
 
 
21 February 2024 
2. 
McDonald C, Rees J, Winge K, Newton JL, Burn DJ. Bladder training for urinary 
tract symptoms in Parkinson disease: A randomized controlled trial. Neurology. 2020 
Mar 31;94(13):E1427–33.  
3. 
Rizvi RM, Chughtai NG, Kapadia N. Effects of Bladder Training and Pelvic Floor 
Muscle Training in Female Patients with Overactive Bladder Syndrome: A 
Randomized Controlled Trial. Urol Int. 2018;100(4):420–7.  
4. 
Yoon HS, Song HH, Ro YJ. A comparison of effectiveness of bladder training and 
pelvic muscle exercise on female urinary incontinence. Vol. 40, International Journal 
of Nursing Studies. 2003.  
5. 
Ellahi A, Stewart F, Kidd EA, Griffiths R, Fernandez R, Omar MI. Strategies for the 
removal of short-term indwelling urethral catheters in adults. Cochrane Database Syst 
Rev. 2021 Jun 29;6(6):CD004011.  
6. 
Zhengyong Y, Changxiao H, Shibing Y, Caiwen W. Randomized controlled trial on 
the efficacy of bladder training before removing the indwelling urinary catheter in 
patients with acute urinary retention associated with benign prostatic hyperplasia. 
Scand J Urol. 2014 Aug;48(4):400–4.  
7. 
Fanfani F, Costantini B, Mascilini F, Vizzielli G, Gallotta V, Vigliotta M, et al. Early 
postoperative bladder training in patients submitted to radical hysterectomy: is it still 
necessary? A randomized trial. Arch Gynecol Obstet. 2015 Apr;291(4):883–8.  
8. 
谢宇红, 王枭杰, 陈致奋, 池畔, 官国先, 林惠铭, et al. 中低位直肠癌术后男性
患者行膀胱锻炼对膀胱功能恢复影响的前瞻性随机对照研究. 中华胃肠外科杂
志. 2018;21(11):6.  
9. 
Markopoulos G, Kitridis D, Tsikopoulos K, Georgiannos D, Bisbinas I. Bladder 
training prior to urinary catheter removal in total joint arthroplasty. A randomized 
controlled trial. Int J Nurs Stud. 2019 Jan;89:14–7.  
10. 
Muge Catikkas N, Merve Oren M, Ozturk GB. Effect of bladder training on post 
catheterization urinary retention remains to be resolved. Int J Nurs Stud. 2020 
Jan;101:103399.  
11. 
Gaither TW, Patel P, Del Rosario C, Baxter ZC, Pannell S, Dunn M. Predictive Value 
of Voiding Efficiency After Active Void Trial in Men Undergoing BPH Surgery. 
Urology. 2022 Oct;168:169–74.  
12. 
Wong MC, Isaacson K, Morris S. Into the void: a review of postoperative urinary 
retention after minimally invasive gynecologic surgery. Curr Opin Obstet Gynecol. 
2018 Aug;30(4):260–6.  
13. 
Stav K, Rappaport YH, Beberashvili I, Zisman A. Pain Associated With Urethral 
Catheterization Is Reduced in Males by Simultaneous Voiding Maneuver. Urology. 
2017 Apr;102:21–5.  
14. 
Braschinsky M, Zopp I, Kals M, Haldre S, Gross-Paju K. Bladder dysfunction in 
hereditary spastic paraplegia: what to expect? J Neurol Neurosurg Psychiatry. 2010 
Mar;81(3):263–6.  
15. 
Wei B, Zheng Z, Fang J, Xiao J, Han F, Huang M, et al. Effect of Denonvilliers’ 
Fascia Preservation Versus Resection During Laparoscopic Total Mesorectal Excision 
on Postoperative Urogenital Function of Male Rectal Cancer Patients: Initial Results 
of Chinese PUF-01 Randomized Clinical Trial. Ann Surg. 2021 Dec 1;274(6):e473–

 
35/ 41 
Version 
1.1.1
 
 
21 February 2024 
80.  
16. 
Sadakari Y, Hisano K, Sada M, Mizuuchi Y, Nagayoshi K, Fujita H, et al. Long-term 
effects of laparoscopic lateral pelvic lymph node dissection on urinary retention in 
rectal cancer. Surg Endosc. 2022 Feb;36(2):999–1007.  
17. 
Lee YH, Lee JE, Ryu DW, Oh YS, Lee KS, Hong SH, et al. Urinary Dysfunctions and 
Post-Void Residual Urine in Typical and Atypical Parkinson Diseases. J Parkinsons 
Dis. 2018;8(1):145–52.  
18. 
Kneist W, Kauff DW, Juhre V, Hoffmann KP, Lang H. Is intraoperative 
neuromonitoring associated with better functional outcome in patients undergoing 
open TME? Results of a case-control study. Eur J Surg Oncol. 2013 Sep;39(9):994–9.  
  
 
 

 
36/ 41 
Version 
1.1.1
 
 
21 February 2024 
Appendix 1: IPSS Score 
Symptom 
Question 
Score 
Incomplete 
Emptying 
Over the past month, how often have 
you had a sensation of not emptying 
your bladder completely after you 
finished urinating? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Frequency 
Over the past month, how often have 
you had to urinate again less than two 
hours after you finished urinating? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Intermittency 
Over the past month, how often have 
you found you stopped and started 
again several times when you 
urinated? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Urgency 
Over the past month, how difficult 
have you found it to postpone 
urination? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Weak Stream 
Over the past month, how often have 
you had a weak urinary stream? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Straining 
Over the past month, how often have 
you had to push or strain to begin 
urination? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Nocturia 
Over the past month, how many times 
did you typically get up at night to 
urinate? 
0: None 
1: 1 time 
2: 2 times 
3: 3 times 
4: 4 times 

 
37/ 41 
Version 
1.1.1
 
 
21 February 2024 
5: 5 or more times 
1.Total Score Calculation: Sum the scores of the above 7 items. The total score ranges 
from 0 to 35. 
①Mild symptoms: 0 - 7 ②Moderate symptoms: 8 - 19 ③Severe symptoms: 20 - 35 
 
 
 

 
38/ 41 
Version 
1.1.1
 
 
21 February 2024 
Appendix 2: ICIQ-SF Score 
International Consultation on Incontinence Questionnaire - Urinary Incontinence 
Short Form (ICIQ-UI SF) 
1.Please write in your date of birth: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
2.Are you (check one):  Female  Male 
3.How often do you leak urine? Check one box. 
0  Never 
1  About once a week or less often 
2  Two or three times a week 
3  About once a day 
4  Several times a day 
5  All the time 
4.We would like to know how much urine you think leaks. How much urine do you 
usually leak (whether you wear protection or not)? Check one box. 
 0  None 
 2  A small amount 
 4  A moderate amount 
 6  A large amount 
5.Overall, how much does leaking urine interfere with your everyday life? Please 
circle a number between 0 (not at all) and 10 (a great deal) 
  0 1 2 3 4 5 6 7 8 9 10 
Not at all A great deal 
ICIQ score: Sum scores 3 + 4 + 5 
6.When does urine leak? Please check all that apply to you. 
 Never – urine does not leak 
 Leaks before you can get to the bathroom 
 Leaks when you cough or sneeze 
 Leaks when you are asleep 
 Leaks when you are physically active / exercising 
 Leaks when you have finished urinating and are dressed 
 Leaks for no obvious reason 
 Leaks all the time 
 
 
 
 
 
 
 
 

 
39/ 41 
Version 
1.1.1
 
 
21 February 2024 
Appendix 3: CRBD Grading Assessment 
Grading 
Symptoms 
Grade 0 
No discomfort at all 
Grade 1 
Only informed of urethral discomfort when asked and it is 
tolerable. 
Grade 2 
The patient actively informed of urgency, dysuria and lower 
abdominal distension, but without behavioral response 
Grade 3 
The patient actively informed of urgency, dysuria and lower 
abdominal distension, accompanied by behavioral responses 
(such as severe restlessness, limb movement, attempting to 
remove the catheter), requiring medical staff to restrain and 
multiple caregivers to watch. 
 
 
 
 
 
 

 
40/ 41 
Version 
1.1.1
 
 
21 February 2024 
Appendix 4: Bladder Training Quality Self-Assessment Form 
1.Total number of times the catheter was clamped? 
2.Did you feel the urge to urinate each time during the clamping training? 
□ Every time； 
□ More than half of the times; 
□ Less than half of the times; 
□ Never 
3.Were you able to hold for 3 hours before releasing the catheter? 
□ Every time； 
□ More than half of the times; 
□ Less than half of the times; 
□ Never 
4.Did you cooperate with the urination action after releasing the catheter? 
□ Every time； 
□ More than half of the times; 
□ Less than half of the times; 
□ Never 
 
 
 

 
41/ 41 
Version 
1.1.1
 
 
21 February 2024 
Appendix 5: Postoperative Complications Clavien-Dindo System Grading. 
Grading 
Definition 
I 
Postoperative complications that do not require drug, 
surgical, endoscopic, or radiological intervention, but include 
drug therapy such as anti-emetics, antipyretics, analgesics, 
diuretics, electrolytes, physiotherapy, and also include incisional 
infections that are opened at the bedside; 
II 
Requires drug therapy, excluding patients who only received 
Grade I medication, incisional infections requiring antibiotic 
treatment, and includes blood transfusions and total parenteral 
nutrition 
III 
Requires surgical, endoscopic, or radiological intervention 
 
III
a 
Does not require general anesthesia 
III
b 
Requires general anesthesia 
IV 
Life-threatening complications (including central nervous 
system complications) requiring IC (intermediate care) or ICU 
management 
 
IV
a 
Organ failure (including dialysis) 
IV
b 
Multi-organ failure 
V 
Death 
 
 
 
 

 
1/ 48 
Version 
2.0
 
 
5 January 2025 
The effect of intermittent catheter clamping combined with active urination 
training (ICCAUT) on urinary dysfunction after radical resection of rectal 
cancer: a single-center randomized controlled trial 
 
 
 
 
 
Principal Investigator: Yuchen Guo，Tingting He 
Department: Gastrocolorectal Surgery, General Surgery Center 
Version number：V 2.0 
Version date：January 5, 2025 
 
 
 
 

 
2/ 48 
Version 
2.0
 
 
5 January 2025 
Content 
1. Background and Rationale ........................................................................................................... 4 
2. Research Objectives and Endpoints ............................................................................................. 6 
2.1 Objective ............................................................................................................................ 6 
2.2 Study Endpoint ................................................................................................................... 7 
2.2.1 Primary Study Endpoint and Definition .................................................................. 7 
2.2.2 Secondary study endpoints and definitions. ............................................................. 8 
2.2.3 Other indicators and definitions. .............................................................................. 8 
3.Study design. ................................................................................................................................. 9 
3.1 Overall study design. .......................................................................................................... 9 
3.2 Study duration. ................................................................................................................... 9 
3.3 Trial flowchart .................................................................................................................... 9 
4. Population. .................................................................................................................................. 10 
4.1 Inclusion criteria ............................................................................................................... 10 
4.2 Exclusion criteria .............................................................................................................. 11 
5. Study treatment groups. .............................................................................................................. 12 
5.1 Randomization and group assignment. ............................................................................. 12 
5.1.1 Methods for Generating Random Sequences ......................................................... 12 
5.1.2 Randomization concealment. ................................................................................. 13 
5.2 Blinding and Unblinding. ................................................................................................. 13 
6. Study procedure .......................................................................................................................... 14 
6.1 Study treatment period. .................................................................................................... 14 
6.1.1 Patient recruitment and randomization. ................................................................. 14 
6.1.2 Intervention ............................................................................................................ 15 
6.1.3 Discharge and follow-up. ....................................................................................... 16 
6.2 Concomitant treatment, follow-up .................................................................................... 18 
6.3 Patient compliance and withdrawal .................................................................................. 18 
6.4 Protocol deviations ........................................................................................................... 19 
7.Evaluation .................................................................................................................................... 19 
7.1 Efficacy evaluation ........................................................................................................... 19 
7.2 Safety evaluation .............................................................................................................. 19 
7.2.1 Baseline vital signs and symptoms ........................................................................ 19 
7.2.2 Laboratory examinations ....................................................................................... 20 
7.2.3 Physical examination and vital signs ..................................................................... 20 
8. Adverse event reporting .............................................................................................................. 21 
8.1 Adverse events .................................................................................................................. 21 
8.2 Definition of adverse events ............................................................................................. 21 
8.3 Abnormal test results. ....................................................................................................... 21 
8.4 Serious adverse events ...................................................................................................... 21 
8.5 Severity assessment .......................................................................................................... 22 
8.6 Causality assessment ........................................................................................................ 22 
9. Data processing and storage ....................................................................................................... 22 
10. Quality management ................................................................................................................. 22 
11. Statistical analysis .................................................................................................................... 25 

 
3/ 48 
Version 
2.0
 
 
5 January 2025 
11.1 Sample size determination .............................................................................................. 25 
11.2 Analysis population ........................................................................................................ 26 
11.2.1 Full analysis set .................................................................................................... 26 
11.2.2 Per-protocol analysis set ...................................................................................... 26 
11.2.3 As-treated analysis set .......................................................................................... 27 
11.3 Missing data and its handling approaches ...................................................................... 27 
11.3.1 Definition of Missing Data .................................................................................. 27 
11.3.2 Methods for handling missing data ...................................................................... 28 
11.4 Efficacy analysis and statistical methods ........................................................................ 32 
11.4.1 Analysis of the primary endpoint ......................................................................... 32 
11.4.2 Sensitivity Analysis of the Primary Endpoint ...................................................... 32 
11.4.3 Analysis of secondary endpoints .......................................................................... 33 
11.4.4 Subgroup analysis ................................................................................................ 34 
11.5 Exploratory Analysis ...................................................................................................... 34 
11.6 Interim analysis ............................................................................................................... 34 
11.7 Final analysis .................................................................................................................. 34 
11.8 Data Monitoring Committee ........................................................................................... 35 
12. Data collection and management .............................................................................................. 35 
12.1 Case Report Form/Electronic Data Recording ............................................................... 35 
12.2 Data management ........................................................................................................... 37 
13. Ethics and Morality .................................................................................................................. 37 
13.1 Ethics committee ............................................................................................................ 37 
13.2 Patient information and informed consent ...................................................................... 38 
14. Definition of study completion ................................................................................................. 38 
15. Trial organizational structure .................................................................................................... 38 
16. Confidentiality and data security .............................................................................................. 39 
17. Insurance and compensation. .................................................................................................... 39 
18. Publication statement ............................................................................................................... 40 
19.References ................................................................................................................................. 40 
Appendix 1: IPSS Score ................................................................................................................. 42 
Appendix 2: ICIQ-SF Score ........................................................................................................... 44 
Appendix 3: CRBD Grading Assessment ...................................................................................... 46 
Appendix 4: Bladder Training Quality Self-Assessment Form ...................................................... 47 
Appendix 5: Postoperative Complications Clavien-Dindo System Grading. ................................. 48 
 
 
 
 

 
4/ 48 
Version 
2.0
 
 
5 January 2025 
1. Background and Rationale 
Gastrointestinal surgery usually requires the placement of a urinary catheter 
during the operation, which is removed after the surgery. For upper gastrointestinal 
surgery, since there is no surgical manipulation of the pelvic and abdominal organs, 
the catheter is usually removed within 2 days after the operation, and urinary retention 
rarely occurs. However, in rectal surgery, which is performed in the pelvic cavity, the 
resection requires the ligation at the root of the inferior mesenteric artery to achieve 
the third station lymph node dissection. During this process, there is a possibility of 
damaging the upper hypogastric plexus and the pelvic nerve plexus. Damage to these 
nerves, along with other potential perioperative factors, can lead to urinary retention 
in patients after rectal surgery, resulting in a significantly increased rate of secondary 
catheterization. Therefore, reducing postoperative urinary retention and the rate of 
secondary catheterization is one of the clinical issues that need to be addressed. 
Bladder training is a method commonly used by surgeons in clinical practice. In 
a clinical study conducted by Williamson in 1982, it was indicated that intermittently 
clamping the catheter before catheter removal may shorten the time required for 
patients to regain bladder function(1).In this procedure, the patient's urinary catheter 
is first clamped.  After clamping for three hours, the catheter is released to allow the 
urine in the bladder to be drained through the catheter.  This cycle is repeated 
multiple times.  It is widely applied across various departments in clinical settings.  
Current research has confirmed that bladder training can be used as a treatment 
method for overactive bladder syndrome, which can reduce the frequency of urination 
and alleviate symptoms of urinary frequency and urgency(2,3).For patients with 
urinary incontinence, bladder training also has a certain therapeutic effect(4).However, 
the effect of bladder training on reducing urinary retention and secondary 
catheterization rates in patients remains debatable. A recent systematic review 
published in the Cochrane suggests that compared with direct catheter removal, 
bladder training through intermittent urethral catheter clamping may not be sufficient 

 
5/ 48 
Version 
2.0
 
 
5 January 2025 
to reduce the rate of secondary catheterization in patients(5).In addition, the procedure 
of bladder training may actually increase the rate of urinary tract infections in 
patients(6).At present, the number of RCT studies on bladder training through 
intermittent urethral catheter clamping is limited, and no advantage has been found 
compared to free-drainage in reducing the rate of secondary catheterization. 
It is worth noting that the quality of  RCT trials on the impact of bladder training on 
post-pelvic surgery urinary retention is inconsistent, with study designs that suffer fro
m inadequate basis for sample size calculation, insufficient sample sizes, and low stati
stical power.Additionally, most of the relevant RCT studies have not been conducted 
in strict accordance with the RCT trial process and have not been registered, casting 
doubt on their quality and credibility, making it difficult to derive reliable clinical 
practice evidence from them(6-9).At present, there is no consensus among clinicians 
regarding this issue. Although current guidelines related to urinary catheter care tend 
to suggest that intermittent clamping of the urinary catheter for bladder function 
training cannot effectively reduce the incidence of urinary retention and may even 
increase the incidence of urinary tract infections in patients. However, since most of 
the existing relevant studies are mainly retrospective studies and lack high-quality 
RCT trials, the recommendations in the published guidelines regarding whether to 
conduct bladder training before removing the urinary catheter are all based on 
low-quality research evidence. In clinical practice, especially for patients after low 
radical resection of rectal cancer many centers still perform intermittent urethral 
catheter clamping for bladder training to reduce the incidence of urinary retention and 
the rate of secondary catheterization. In 2020, Muge et al. also published a comment 
in a top nursing journal, pointing out that the impact of postoperative bladder training 
on urinary retention still requires further research(10).Therefore, high-quality clinical 
studies are needed to explore the effectiveness of bladder training. 
In this study, we plan to conduct intermittent clamping of the urinary catheter for 
patients to explore the impact of this procedure on postoperative urinary dysfunction 
after radical resection of rectal cancer. Unlike previous studies, on the basis of 
intermittent clamping of the urinary catheter, we have combined active urination 

 
6/ 48 
Version 
2.0
 
 
5 January 2025 
training, which means instructing patients to perform active urination movements 
during the intervals when the catheter is opened, to assist in the emptying of urine 
from the bladder. In recent years, studies have shown that active urination training to 
calculate the efficiency of urination can effectively predict the occurrence of urinary 
retention in patients(11,12). However, there are no studies on the impact of active 
urination training on urinary retention. Theoretically, intermittent catheter clamping 
combined with active urination training can simulate the normal micturition process 
of patients. In addition, studies have shown that active urination training can alleviate 
catheter-related pain in patients(13).Therefore, in this study, we combined intermittent 
urethral catheter clamping training with active urination training. We named this 
urinary catheter management strategy the ICCAUT（intermittent catheterization clamp 
combined with active urination training） management strategy. Currently, there are 
no registered RCT studies on how ICCAUT management strategies affect the 
postoperative urinary function of patients after radical resection of rectal cancer. 
Therefore, this study aims to conduct a prospective randomized controlled trial. It will 
explore whether the ICCAUT management strategy, compared with the free-drainage 
strategy, can affect postoperative urinary dysfunction in patients after proctectomy, 
aiming to provide high-level evidence for clinical practice. 
2. Research Objectives and Endpoints 
2.1 Objective 
Primary Objective 
This study investigated the effects of intermittent catheter clamping combined 
with active urination training (ICCAUT) on postoperative urinary dysfunction in 
patients after proctectomy.  
Secondary Objective 
To explore whether bladder training will increase the risk of postoperative 
urinary tract infections in patients after radical resection of rectal cancer. 

 
7/ 48 
Version 
2.0
 
 
5 January 2025 
2.2 Study Endpoint 
2.2.1 Primary Study Endpoint and Definition 
The primary endpoint of the study is urinary dysfunction in patients within 7 
days after catheter removal. In this study, urinary dysfunction was defined as 
incomplete bladder emptying after the first voiding following catheter removal or an 
inability to urinate requiring a second catheterization. 
Incomplete bladder emptying was characterized by a postvoid residual urine 
volume (PRUV) exceeding 100 mL (14–18).The residual urine volume in the bladder 
after the first urination will be estimated immediately following the first urination 
using bladder ultrasound. The calculation formula is: Bladder urine volume = 
Anteroposterior diameter * Vertical diameter * Transverse diameter * 0.52. The 
bladder ultrasound is performed by a fixed radiologist from the ultrasound imaging 
department, who is exclusively assigned to our department. 
The criteria for determining whether secondary catheterization is needed due to 
difficulty in urination are as follows: 1)The patient is unable to urinate within 10 
hours after catheter removal, and percussion of the bladder upper border indicates that 
it is located above the pubic bone, with an estimated residual urine volume in the 
bladder greater than 200 ml using bedside bladder ultrasound; 2)Although the patient 
is able to urinate after catheter removal, they still feel lower abdominal distension 
after multiple attempts to urinate, and percussion by the physician indicates that the 
bladder upper border is located above the pubic bone, with an estimated residual urine 
volume in the bladder greater than 200 ml using bedside bladder ultrasound. 
In the determination of the primary endpoint, patients who undergo secondary 
catheterization for reasons other than urinary retention will also be recorded as 
primary endpoint events, but sensitivity analysis shall be conducted on these patients 
in the sensitivity analysis. The specific analysis method is described in the section on 
sensitivity analysis of the primary endpoint in the statistical analysis. Such events may 
include the following scenarios:  

 
8/ 48 
Version 
2.0
 
 
5 January 2025 
1) The patient requests secondary catheterization due to urgent urination or 
intense bloating, but the urine volume withdrawn after secondary catheterization does 
not exceed 100 ml;  
2) The patient requires secondary catheterization due to disease-related factors 
(such as secondary surgery, urethral injury, shock, altered consciousness, intestinal 
obstruction, hemorrhage, transfer to ICU, SOFA score ≥2, etc.). 
2.2.2 Secondary study endpoints and definitions. 
Secondary endpoints of this study include: 1) Catheter-associated urinary tract 
infection status; 2) Time to first urination after catheter removal; 3) Grading 
assessment of catheter-related bladder discomfort (CRBD); 4) Post-catheter removal 
urinary function evaluation (using ICIQ-SF and IPSS scores); 5) Postoperative 
complications within 30 days (incidence of complications, types of complications, and 
grading of complications); 6) Incidence of residual urine volume greater than 200 
milliliters after the first urination. 
2.2.3 Other indicators and definitions. 
Urinary tract infection is defined as an inflammatory response of the urinary 
epithelium to bacterial invasion. The diagnosis requires both of the following criteria 
to be met: 1) Urinalysis indicates a bacterial count above the normal upper limit, and 
2) Positive urine culture. The time to first urination after catheter removal is defined 
as the time from the removal of the catheter to the patient's spontaneous urination, 
measured in hours. The time from the second catheterization to the removal of the 
urinary catheter is defined as the time interval from the first removal of the urinary 
catheter to the completion of catheter insertion by the nurse or suprapubic puncture by 
the ultrasound doctor after the clinician determines that the patient requires a second 
catheterization. 
Complications within 30 days after surgery are assessed according to the 
Clavien-Dindo classification, and complications of grade II and above are recorded 
and analyzed. These include, but are not limited to, intraperitoneal bleeding, 

 
9/ 48 
Version 
2.0
 
 
5 January 2025 
gastrointestinal bleeding, anastomotic leak, chylous fistula, surgical site infection 
(intra-abdominal infection and incisional infection), intestinal obstruction, 
postoperative diarrhea, pulmonary infection, urinary tract infection, cardiovascular 
accident, cerebrovascular accident, and thrombotic diseases. 
3.Study design. 
3.1 Overall study design. 
Single-center, prospective, two-arm, parallel-group randomized controlled study. 
3.2 Study duration. 
This study plans to complete patient enrollment within one year. The 
postoperative follow-up period for patients is one month. The entire study, including 
the establishment of the study, patient recruitment, patient follow-up, and data 
analysis, is expected to last for two years. We will conduct the primary endpoint 
analysis after all patients have completed their first postoperative month follow-up. 
The study will begin in February 2024 at the First Hospital of Jilin University. 
3.3 Trial flowchart 
 
As shown in Figure 1. 

 
10/ 48 
Version 
2.0
 
 
5 January 2025 
 
Figure 1 Trial flowchart 
4. Population. 
4.1 Inclusion criteria  
1) Patients with a confirmed preoperative diagnosis of rectal cancer; 
2) Preoperative colon CT or rectal MR confirms that the lower edge of the tumor 
is located in the rectum (including the rectal and anal canal regions) below the 

 
11/ 48 
Version 
2.0
 
 
5 January 2025 
rectosigmoid junction (12 cm from the anal verge); 
3) Patients undergoing laparoscopic or robotic-assisted low anterior resection or 
abdominoperineal resection for rectal cancer. 
4.2 Exclusion criteria 
1) History of abdominal surgery involving the rectum, sigmoid colon, left 
hemicolectomy, bladder resection or partial resection, prostate surgery, or 
hysterectomy. 
2) History of urethral injury, cranial surgery, spinal surgery, stroke with limb 
dysfunction, or Parkinson's disease. 
3) Inability to urinate through the urethra preoperatively due to various reasons 
(e.g., ureteral puncture or ureterostomy). 
4) Presence of urinary tract infection preoperatively. 
5) Previously diagnosed with bladder overactivity syndrome, urinary retention or 
voiding dysfunction, or diabetic bladder disease. 
6) Concomitant resection of other pelvic organs was performed during surgery, 
including the bladder, prostate, uterus, cervix, and vagina, except for simple adnexal 
resection. 
7) Lateral lymph node dissection for rectal cancer. 
8) Injury to the ureter, bladder, or urethra during the perioperative period. 
9) Preoperative renal dysfunction (serum creatinine level >133 μmol/L). 
10) Emergency surgery. 
11) Male patients with preoperative benign prostatic hyperplasia receive 
medication treatment. 
12) Patients with a ureteral stent or ureteral stricture, or bilateral hydronephrosis. 
13) Conversion to open surgery. 

 
12/ 48 
Version 
2.0
 
 
5 January 2025 
5. Study treatment groups. 
ICCAUT group (Experimental group): Patients underwent laparoscopic or 
robotic rectal cancer TME surgery, and bladder function exercises were initiated 
through intermittent catheter clamping at 9:00 am on the first postoperative day, with 
the urinary catheter removed at 9:00 am on the second postoperative day. 
Free-drainage group (Control group): Patients underwent laparoscopic or robotic 
rectal cancer TME surgery, with the urinary catheter kept open postoperatively, and it 
was removed at 9:00 am on the second postoperative day. 
Physicians need to determine whether to remove the urinary catheter according 
to the planned date based on a comprehensive assessment of the patient's 
consciousness, postoperative renal function, circulatory status, and other factors. 
Using the Sequential Organ Failure Assessment (SOFA) score as a reference, if the 
patient's SOFA score is less than 2, the catheter will be removed as planned during the 
day on the second postoperative day. If the SOFA score is 2 or higher, the duration of 
catheter placement should be extended. The specific situation still requires a 
comprehensive judgment by the physician. If the catheter is not removed as planned, 
the reason must be stated in the CRF form. Additionally, if a patient is suspected of 
having a urinary tract infection during catheter training, the clinical physician may 
decide to stop the catheter exercise. 
5.1 Randomization and group assignment. 
5.1.1 Methods for Generating Random Sequences 
Patients who meet the inclusion criteria will be randomly assigned to either the 
bladder training group or the direct removal group. Stratified randomization will be 
performed based on the following three factors, with randomization information 
generated using R language on a computer. The stratification factors are: 1) Gender; 2) 
Whether undergoing abdominoperineal resection (APR). The randomization ratio 

 
13/ 48 
Version 
2.0
 
 
5 January 2025 
between the ICCAUT group and the Free-drainage group is 1:1. A random number 
table manager (RNTM) (Yanhua Wu) from the Research Centre of Clinical 
Epidemiology (RCCE) at Jilin University First Hospital generates and preserves the 
random number table and allocates the randomization information. The RNTM is 
independent of other researchers in this trial. 
5.1.2 Randomization concealment. 
After the random number table is generated through R by RNTM, the random 
allocation information will be printed on paper strips and placed into opaque 
envelopes. The random number table and random allocation information will be kept 
by the RNTM from the RCCE. After clinical doctors and bedside nurses complete the 
patient screening and determine that a patient meets the inclusion criteria for 
enrollment, random allocation can be conducted. The random allocation will take 
place between 6:00 a.m. and 7:00 a.m. on the first day after the patient's surgery, 
before the intervention procedure. Clinical doctors and bedside nurses will submit an 
enrollment application to the RNTM and provide the patient's gender information and 
whether they have undergone an APR surgery. Based on the stratification 
corresponding to these two factors, the RNTM will deliver the opaque envelopes 
containing the random allocation information to the bedside nurse before 8:00 a.m. on 
the first day after surgery. The bedside nurse will then open the envelope and perform 
corresponding procedures on the patient according to the grouping information inside. 
The RNTM is independent of other personnel involved in this study, do not 
participate in any other clinical operations of this study, and have no knowledge of 
any other information about the patients. 
5.2 Blinding and Unblinding. 
This study is blinded to the physician group, the ultrasound imaging physicians 
who assess bladder residual urine volume, and the data analysts. The study group 
requires patients and assigned nurses to keep the patient's group assignment 

 
14/ 48 
Version 
2.0
 
 
5 January 2025 
confidential from the assigned physicians and bladder ultrasound physicians. Since 
the clinical operations are performed by the assigned nurses on the patients, this study 
cannot blind the patients and assigned nurses. The time of unblinding is at the time of 
patient discharge, and any premature unblinding will be recorded.  
6. Study procedure 
6.1 Study treatment period. 
As shown in Table 1  
6.1.1 Patient recruitment and randomization. 
1）After admission, patients are initially assessed to determine if they meet the 
inclusion criteria. If they do, urinalysis and urine culture are performed. The patient's 
urinary function is evaluated using the International Prostate Symptom Score (IPSS) 
(Appendix 1) and the International Consultation on Incontinence Questionnaire Short 
Form (ICIQ-SF) (Appendix 2), and baseline data are collected. 
2）Participants will undergo laparoscopic or robotic‑assisted radical resection of 
rectal cancer. For patients with a narrow pelvic cavity or ultra‑low rectal tumors 
scheduled to receive low anterior resection (LAR), either transanal total mesorectal 
excision (TaTME) or the Turnbull‑Cutait pull‑through procedure combined with 
two‑stage hand‑sewn coloanal anastomosis (TCA) will be employed. The second 
stage of the TCA procedure will be performed 2 to 3 weeks following the initial 
operation. All surgeons will be required to perform high ligation of the inferior 
mesenteric artery (IMA) and to preserve Denonvilliers' fascia. The decision to 
perform APR will be based on the patient's tumor stage and the outcome of 
communication between the surgeon and the patient. After surgery, patients are 
reassessed to determine if they still meet the inclusion criteria and are checked against 
each exclusion criterion. If they are not excluded, they are deemed suitable for 
enrollment. The patient is then informed and asked to sign the informed consent. If 

 
15/ 48 
Version 
2.0
 
 
5 January 2025 
the patient is informed and agrees to participate, the informed consent form is signed, 
and randomization begins. Baseline data and surgical-related data for the enrolled 
patients are then collected and completed. 
3）Based on stratification factors, randomization is conducted on a computer. 
The randomization information will be delivered to the assigned nurse via an 
envelope before 8:00 am on the day following surgery. The nurse will then perform 
the intervention according to the group assignment indicated in the envelope. 
6.1.2 Intervention 
On the day following surgery (postoperative day 1) at 9:00 am, the nurse will 
perform the corresponding intervention operations for patients in both groups based 
on the group assignment indicated in the randomization envelope. Before the 
intervention, both groups of patients must complete the CRBD (Catheter-Related 
Bladder Discomfort) grading assessment by the assigned nurse (Appendix 3). During 
the patient's first catheterization, the use of selective α1-adrenergic receptor blockers 
(such as tamsulosin) is not permitted. 
1）The ICCAUT strategy included intermittent urethral catheter clamping and 
active urination training. In the ICCAUT group, intermittent catheter clamping was 
initiated at 9:00 am on the first postoperative day. In each cycle, the catheter was 
clamped for 3 h, followed by a 5-min release. The next cycle began as soon as the 
previous cycle had been completed. Catheter training concluded at 10:00 pm on the 
frst postoperative day, and the catheter was left open during the night. The urinary 
catheter was removed on the second postoperative day, and the training did not stop 
until the catheter had been removed. During the training period, if the patient 
experienced a strong urge to urinate before the 3-h clamping time was over, the 
clamping could be released in advance for 5 min, allowing the patient to proceed to 
the next cycle of bladder training. Each time the catheter was released, the patients 
were encouraged to actively initiate urination to facilitate complete bladder emptying. 
We refer to this catheter management strategy, which involves intermittent clamping 
of the catheter and active urination during the release periods, as the ICCAUT 

 
16/ 48 
Version 
2.0
 
 
5 January 2025 
management strategy. 
2）For patients in the free-draining group, no intervention was performed using a 
catheter during this period. The urinary catheter was removed at 9:00 am on the 
second postoperative day. 
3）Before the urinary catheter is removed on the second day, both groups of 
patients must complete the CRBD (Catheter-Related Bladder Discomfort) grading 
assessment again by the assigned nurse (Appendix 3), and urine samples must be 
collected for urinalysis and urine culture. Additionally, patients in the ICCAUT group 
must scan a code to fill out the Bladder Training Quality Self-Assessment Form 
(Appendix 4) before the catheter is first removed. After the catheter is removed, the 
time from the first catheter removal to the first urination, as well as the volume of the 
first urination, should be recorded for both groups of patients. 
4）Immediately after the first urination, a bladder ultrasound must be performed 
to assess the residual urine volume in the bladder. The bladder ultrasound is 
conducted by a fixed radiologist from the ultrasound imaging department, who is 
exclusively assigned to our department and is located in the same therapeutic area as 
the patient. After the urinary catheter is removed, the patient must be observed and the 
situation of any secondary catheterization must be recorded. The observation period is 
the following 7 days after first urinary catheter removal. For patients who undergo 
secondary catheterization, the time from the first catheter removal to the secondary 
catheterization, the volume of urine drained after secondary catheterization, the 
method of secondary catheterization, and the reason for secondary catheterization 
must be recorded. 
5）Record the IPSS score and ICIQ-SF score of the patient on the day following 
the first catheter removal (excluding patients who underwent secondary 
catheterization). Record complications within 30 days after surgery and their 
Clavien-Dindo classification (Appendix 5). 
6.1.3 Discharge and follow-up. 
    After discharge, when the patient returns for a follow-up visit one month after 

 
17/ 48 
Version 
2.0
 
 
5 January 2025 
surgery, the physician must collect information on complications and their grading 
within the first postoperative month, and conduct an assessment using the one-month 
postoperative urinary function score form. 
Table 1: Study Enrollment, Intervention, and Outcome Assessment Form 
 
 
Study phase 
 
Recruitmen
t 
Surgery and 
randomizatio
n 
 
Post-randomization 
                      Time point 
Item 
Pre-random
ization 
0 
Before 
catheter 
removal 
After 
catheter 
removal 
One month postoperatively 
Enrollment： 
 
 
 
 
 
 
Screen suitable population 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
Baseline and surgery-related data 
collection 
X 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Intervention： 
 
 
 
 
 
 
ICCAUT group 
 
 
X 
 
 
 
  Free-drainage group 
 
 
X 
 
 
 
Assessment: 
 
 
 
 
 
 
Bladder residual urine volume and 
secondary catheterization record 
 
 
 
X 
 
 
Record of information after catheter 
removal 
 
 
 
X 
 
 
Catheter-related bladder discomfort 
(CRBD) grading assessment 
 
 
X 
 
 
 
Bladder training self-assessment form 
 
 
X 
 
 
 
Urinalysis and urine culture 
X 
 
X 
 
 

 
18/ 48 
Version 
2.0
 
 
5 January 2025 
  Urinary function assessment 
X 
 
 
X 
X 
  Postoperative complications and 
grading 
 
 
X 
X 
X 
6.2 Concomitant treatment, follow-up 
The total follow-up time for postoperative patients is one month. The follow-up 
content includes postoperative complications within 30 days, as well as the IPSS and 
ICIQ-SF scores at one month postoperatively. 
The follow-up within the first 30 days after surgery is conducted through 
in-hospital observation, outpatient visits, phone calls, or questionnaires. 
Complications related to the surgery and their grading, as well as the solutions, are 
recorded during this period 
The postoperative chemotherapy regimen for patients will be based on the 
NCCN 2023 Rectal Cancer Treatment Guidelines, which will guide the appropriate 
chemotherapy or systemic treatment. 
6.3 Patient compliance and withdrawal 
If, after randomization, a patient refuses the randomly assigned urinary catheter 
management method at any time during the indwelling urinary catheter period and 
requests to have the intervention carried out according to the other urinary catheter 
management method, the other urinary catheter management method shall be 
provided to the patient in accordance with the patient's wish. If at any time during the 
entire study, a patient requests to withdraw from the study, the principal investigator 
shall communicate with the patient to avoid disrupting the balance of the 
randomization due to the withdrawal. If necessary, the patient's compensation shall be 
increased. If the patient still insists on withdrawing from the study and refuses to 
allow the use of personal data in this research project, the patient shall be withdrawn 
from the study according to the patient's wish, and all data of this patient shall be 
treated as missing data. During the follow-up phase of the primary endpoint, if a 

 
19/ 48 
Version 
2.0
 
 
5 January 2025 
patient refuses to cooperate with the follow-up of the primary endpoint, including the 
follow-up of secondary catheterization and the assessment of residual urine volume, 
the principal investigator shall communicate with the patient and appropriately 
increase the compensation for the subjects to avoid the absence of the primary 
endpoint. If the patient stubbornly refuses to cooperate with the follow-up of the 
primary endpoint, the primary endpoint of the patient shall be treated as missing data, 
and other data shall be recorded in the database.   
6.4 Protocol deviations 
 
Researchers participating in the experiment will follow the experimental 
requirements for the corresponding operations and data recording. Any events that 
deviate from the original trial protocol must be recorded with the time of occurrence 
and specific reasons, and any deviations from the trial protocol must be explained. 
7.Evaluation 
7.1 Efficacy evaluation 
The efficacy evaluation methods for different interventions include, but are not 
limited to: postoperative assessment of symptoms and signs, postoperative ultrasound 
assessment of the urinary system, postoperative evaluation of urination-related 
parameters, postoperative urinalysis and urine culture assessment, and postoperative 
surveys on urination function-related questionnaires. 
7.2 Safety evaluation 
7.2.1 Baseline vital signs and symptoms 
When conducting a safety assessment, it is first necessary to understand the 
baseline vital signs and symptoms of the test subjects. This includes measuring their 

 
20/ 48 
Version 
2.0
 
 
5 January 2025 
body temperature, pulse, respiratory rate, and blood pressure, while noting any 
specific symptoms such as dizziness, nausea, vomiting, etc. Preoperative 
hematological examinations and imaging studies should be completed, along with 
preoperative urinalysis, urine culture, and preoperative voiding function questionnaire 
assessments. Additionally, the patient's medical history must be clarified and 
cross-checked against the trial's inclusion and exclusion criteria one by one to ensure 
that the patient population has no surgical contraindications and fully meets the 
enrollment criteria. These baseline data will serve as reference indicators for the 
assessment. 
7.2.2 Laboratory examinations 
The continuity indicators describe the measured values of each research subject 
after surgery and the change values relative to the preoperative baseline. The 
laboratory indicators are divided into low, normal, and high according to the normal 
value range. Describe the situations where the values change from normal or high at 
baseline to low after baseline, and where the values change from normal or low at 
baseline to high after baseline. The low or high values after baseline are calculated 
using the minimum or maximum observed value after baseline. Doctors will evaluate 
these abnormal indicators to determine whether their abnormalities have clinical 
significance. Describe the proportion of "abnormal and clinically significant" among 
the subjects with abnormal changes. 
7.2.3 Physical examination and vital signs 
Physical Examination: General examination, head examination, neck 
examination, thorax and lung examination, heart and vascular examination, abdominal 
examination, spine and limbs examination, and neurological examination. Vital signs 
include routine blood pressure, heart rate, body temperature, etc. Statistical 
descriptions are provided for the measurement values of physical examination, vital 
signs, and weight before and after treatment relative to the baseline. Abnormal vital 
signs or those exceeding the normal value range are described. 

 
21/ 48 
Version 
2.0
 
 
5 January 2025 
8. Adverse event reporting 
8.1 Adverse events 
Adverse events in the study include complications and death events within 30 
days after surgery. All adverse events reported spontaneously by the subjects or 
observed by the staff will be recorded in the database and promptly reported to the 
trial steering committee. 
8.2 Definition of adverse events 
An adverse event is defined as any untoward experience occurring in a subject 
during the study, regardless of whether it is considered to be related to catheter 
clamping. All adverse events reported spontaneously by the trial subject or observed 
by the investigator or their staff will be recorded. 
8.3 Abnormal test results. 
Abnormal test results should be evaluated to determine whether they should be 
reported as adverse events based on the following criteria for objective test values: 1) 
Test results are accompanied by symptoms; 2) Test results require medical or surgical 
intervention; 3) The investigator considers the test result to be an adverse event. 
If none of the above criteria are met, merely repeating an abnormal test does not 
constitute an adverse event. Test results judged by the investigator to be erroneous do 
not need to be reported as adverse events. 
8.4 Serious adverse events 
Serious adverse events include any of the following adverse medical events: 1) 
Events or effects leading to death; 2) Life-threatening events; 3) Events requiring 
hospitalization or prolonging the hospital stay of an inpatient; 4) Events resulting in 

 
22/ 48 
Version 
2.0
 
 
5 January 2025 
persistent or significant disability or incapacity. Upon learning of a serious adverse 
event that is life-threatening or leads to death, it must be reported within 7 days. Other 
serious adverse events must be reported within 15 days. All adverse events are 
followed up immediately after they occur, until the event stabilizes or improves. 
Depending on the specific situation, follow-up may require additional tests or medical 
procedures, or further referral. 
8.5 Severity assessment 
The severity of adverse events will be assessed using the Clavien-Dindo 
classification of complications. 
8.6 Causality assessment 
The causality of adverse events with respect to the intervention will be 
subjectively assessed by the investigator. 
9. Data processing and storage 
Clinical research data will be recorded through the perioperative eCRF, including 
perioperative information, pathological data, and follow-up information. To protect 
patient privacy, patient identification numbers will not be disclosed to data analysts. 
All patients will be coded and identified using random numbers. These random 
numbers do not include patient initials or date of birth. Members of the trial steering 
committee will have a decoding list that specifies the random numbers of patients in 
the database and their identification numbers. 
10. Quality management 
The key to the quality control of the trial lies in: 
（1）Blinding quality control 

 
23/ 48 
Version 
2.0
 
 
5 January 2025 
The implementation of blinding in this study may affect the quality of the 
research, particularly the achievement of the primary endpoint. If the trial is not 
blinded to surgeons, it may influence their judgment on whether the patient needs 
secondary catheterization based on whether bladder training was performed. If the 
ultrasound imaging physicians are not blinded, it may affect their assessment of 
residual urine volume in the bladder based on their knowledge of the patient's 
intervention. Therefore, blinding the randomization information from surgeons and 
ultrasound imaging physicians is one of the key aspects of quality control in this 
experiment. To this end, the study requires patients and nurses to keep the patient's 
group assignment confidential from surgeons and ultrasound imaging physicians. 
Surgeons and ultrasound physicians must also consciously adhere to the principle of 
not inquiring about the patient's group assignment. Any premature unblinding must be 
recorded, including the reason and time of unblinding. 
（2）Interventional method quality control 
The implementation quality of the interventional method is the second key point 
of quality control in this study. To address this, the study implements quality control 
in the following aspects:1) All assigned nurses receive training, which includes 
standardized procedures for clamping and unclamping the urinary catheter, as well as 
the standardized operation for obtaining urine routine and urine culture before catheter 
removal；2) After the patient signs the informed consent and is enrolled, the assigned 
physician is clearly informed not to provide clinical advice on whether to clamp the 
catheter and not to participate in any operations related to bladder training. 
Additionally, the trial management group communicates with the patient that if the 
assigned physician suggests bladder training, the patient should promptly report to the 
assigned nurse and the trial steering committee. The trial steering committee will then 
communicate again with the assigned physician and emphasize the quality control 
points of the trial；3) The start of training is uniformly set for 9:00 am on the first 
postoperative day, and the removal of the catheter is uniformly set for 9:00 am the 
next day. It is not recommended to advance or delay the catheter removal time. Any 
orders to advance or delay the catheter removal must be communicated to the trial 

 
24/ 48 
Version 
2.0
 
 
5 January 2025 
steering committee members before execution, with reasons provided. If the trial 
steering committee deems the reason valid, the order to advance or delay the catheter 
removal is allowed to be executed；4) Nurses need to educate and guide enrolled 
patients to ensure that patients in the bladder training group actively perform forceful 
urination during each period of unclamping to assist in urine discharge；5) Patients in 
the bladder training group, if unable to persist in reaching the specified catheter 
clamping time (less than 3 hours of catheter clamping before feeling the urge to 
urinate), may end a training cycle early, open the catheter for 5 minutes, and then start 
the next clamping training cycle；6) Before catheter removal, patients in the bladder 
training group must complete the Bladder Training Quality Self-Assessment Form; 7) 
During the first catheterization of the patient, selective α1-adrenergic receptor 
blockers (such as Tamsulosin) should not be used. If it is necessary to use them due to 
the patient's condition, the reasons should be recorded; 8) Each patient enrolled in the 
study will be given a subject compensation of 100 yuan to increase the compliance of 
the enrolled patients and the success rate of follow-up.   
（3）Endpoint quality control 
Our project team requires all levels of physicians in our department to strictly 
follow the bladder residual urine assessment method and the criteria for secondary 
catheterization as stipulated in the project research plan to calculate bladder residual 
urine and decide whether to perform secondary catheterization. To reduce bias in the 
measurement of bladder residual urine, this study implements quality control in the 
following two aspects: 1) A fixed radiologist is responsible for assessing bladder 
residual urine, and this physician has specialized in abdominal digestive and urinary 
system ultrasound examinations for over 10 years; 2) The ultrasound diagnosis 
location is set in the same therapeutic area as the patient, ensuring that patients can 
undergo immediate ultrasound examination after the first urination following catheter 
removal, avoiding the impact on the judgment of residual urine due to a long interval 
between urination and ultrasound examination; 3) For patients who fail to undergo the 
residual urine volume assessment in a timely manner for various reasons after the first 
urination, a bladder ultrasound should be conducted immediately after the second 

 
25/ 48 
Version 
2.0
 
 
5 January 2025 
urination, and this situation should be recorded; 4) For patients whose first urination 
occurs after 18:00 following the removal of the urinary catheter, since the designated 
ultrasound physician for assessment has already left work and is unable to conduct 
on-site assessment, the residual urine volume assessment will be carried out by the 
ultrasound physician on 24-hour duty in the hospital, and this situation should be 
recorded. 
To ensure the collection of primary and secondary endpoints, this study will 
appoint a supervisory nurse to serve as the Clinical Research Coordinator (CRC). The 
CRC will daily verify the patient's enrollment, withdrawal, achievement of primary 
endpoints, and measurement of secondary endpoints. They will remind physicians to 
perform relevant medical orders, nurses to execute medical orders and collect data, 
and patients to fill out the required questionnaires and self-assessment forms in a 
timely manner. Additionally, the study will arrange for two graduate students to work 
with the CRC to promptly enter data into the Electronic Case Report Form (eCRF) 
and the database (Epidata). 
（4）Regular education for healthcare personnel involved in the study. 
The research group of this project will conduct regular education for all 
physicians and nurses involved in the study on a monthly basis. The main content of 
the education includes the three quality control aspects mentioned above: blinding 
quality control, interventional method quality control, and endpoint quality control. 
This ensures that physicians and nurses can strictly follow the quality control 
requirements of the study for related operations and ensures the quality of the 
intervention operations performed by nurses on enrolled patients. 
11. Statistical analysis 
11.1 Sample size determination 
The sample size is calculated based on a differential test, with urinary dysfunction 
as the primary endpoint. Based on our preliminary research results, we estimate the 

 
26/ 48 
Version 
2.0
 
 
5 January 2025 
incidence of urinary dysfunction in the bladder training group is 44.7%, and in the 
direct removal group, it is 59.3%. Patients are randomly assigned to the two groups in 
a 1:1 ratio. With a two-sided significance level α of 0.05 and a power (1-β) of 80%, 
the sample size was calculated using PASS 15 software. Each group, the ICCAUT 
group and the free-drainage group, requires 180 cases. Assuming a dropout rate of 
10%, each group requires 200 cases. Therefore, this trial needs a total of 400 cases. 
11.2 Analysis population 
11.2.1 Full analysis set 
The comparative analysis of the primary outcome will be conducted on the basis 
of the "Intention-to-Treat (ITT)" principle. The ITT analysis will include all patients 
who have undergone randomization. In the ITT analysis, for patients who are 
randomized to the bladder training group but have the urinary catheter removed 
directly without undergoing the training ultimately, they will still be analyzed as part 
of the bladder training group. For patients who are randomized to the direct catheter 
removal group but have received bladder training in the end, they will still be 
analyzed as part of the direct catheter removal group.  
Specific possible reasons for not following the randomization procedure include: 
1) The patient's urine becomes cloudy during the postoperative catheterization period, 
and the physician suspects a urinary tract infection, thus not recommending bladder 
training; 2) The patient cannot tolerate catheter clamping and refuses bladder training; 
3) The patient refuses to follow the assigned procedure; 4) The nurse fails to perform 
the operation according to the assigned method; 5) The catheter is not removed on the 
second postoperative day, either earlier or later. The study needs to record the specific 
reasons for not following the planned procedure. 
11.2.2 Per-protocol analysis set 
In the per-protocol analysis set (PPA), only cases that strictly follow the 
randomization and the assigned treatment plan will be included in the analysis. 

 
27/ 48 
Version 
2.0
 
 
5 January 2025 
Patients who do not receive treatment according to the assigned randomization plan 
will be excluded from the PPA. The patients to be excluded include: 1) Patients whose 
urinary catheters were not removed on the second day after the operation for various 
reasons, either with the removal time advanced or postponed; 2) Patients who did not 
carry out the bladder training strictly according to the plan; 3) Patients who had to use 
selective α1-adrenergic receptor blockers due to their medical conditions during the 
first catheterization. 
11.2.3 As-treated analysis set 
In the as-treated analysis set (ATA), we will analyze patients based on the actual 
treatment they received, rather than the treatment assigned by randomization. The 
ATA analysis set will include all the patients in the ITT analysis set. However, in 
terms of grouping, in the ATA analysis, patients who receive at least one round of 
bladder training are classified as the bladder training group, while those who do not 
receive training are classified as the direct removal group.   
11.3 Missing data and its handling approaches 
11.3.1 Definition of Missing Data 
Since the primary endpoint is a composite endpoint, if a patient fails to achieve 
any of the positive events within the primary endpoint (secondary catheterization or 
residual urine volume > 100 ml) and any of the following situations occurs: 1) the 
residual urine volume after the first urination following the removal of the urinary 
catheter is missing; or 2) the situation of secondary catheterization within 7 days after 
the removal of the urinary catheter is missing, the primary endpoint will be defined as 
missing. The possible reasons for the missing primary endpoint include: 1) loss to 
follow - up or death, making it impossible to know whether secondary catheterization 
occurs within 7 days after the removal of the urinary catheter; 2) after the removal of 
the urinary catheter, due to various reasons, the bladder ultrasound for assessing the 
residual urine volume after the first urination is not carried out in a timely manner; 3) 

 
28/ 48 
Version 
2.0
 
 
5 January 2025 
the patient refuses the researcher to use the data related to the patient's own 
micturition function. 
In the case where a subject refuses the researcher to use their personal data, that 
is, the subject requests to withdraw the informed consent and drop out of this study 
midway, all the data of this patient will be treated as missing data in the ITT analysis. 
If the subject refuses the collection of research data after withdrawal but consents to 
the collection of data before withdrawal, the researcher will treat the data after 
withdrawal as missing values, and the data before withdrawal can be included in the 
analysis. 
11.3.2 Methods for handling missing data 
In this study, if the missing rate of the primary endpoint is less than 5%, no 
imputation of missing data will be done in the analysis of the primary endpoint in the 
ITT, PPA, and ATA sets. During the analysis of the primary outcome, missing data 
will be treated as censored. 
If the missing rate of the primary endpoint is 5% or higher at the end of the study, 
the following procedures will be adopted to handle the data with missing values in 
any variable of the primary endpoint. 
1) When the data on post-void residual urine volume (RUV) by ultrasound after 
the first urination is complete, and the situation of secondary catheterization within 7 
days after the removal of the urinary catheter is also complete. There is no missing 
data. 
2) When the data on post-void RUV by ultrasound after the first urination is 
complete, but the situation of secondary catheterization within 7 days after the 
removal of the urinary catheter is missing. 
If the post-void RUV by ultrasound after the first urination is greater than 100 ml, 
handling method: The primary endpoint is reached (positive), and no imputation of 
missing data for secondary catheterization is performed. 
If the post-void RUV by ultrasound after the first urination is less than or equal 
to 100 ml, handling method: Multiple imputation method is used to impute the 

 
29/ 48 
Version 
2.0
 
 
5 January 2025 
missing data of secondary catheterization. 
3) When the data on post-void RUV by ultrasound after the first urination is 
missing, but the situation of secondary catheterization within 7 days after the removal 
of the urinary catheter is complete. 
If secondary catheterization occurs within 7 days after the removal of the urinary 
catheter, handling method: The primary endpoint is reached (positive), and no 
imputation of missing data for RUV is performed. 
If secondary catheterization does not occur within 7 days after the removal of the 
urinary catheter, and the post-void RUV by ultrasound after the second urination is 
not missing, handling method: The Last Observation Carried Forward (LOCF) 
method is used to impute the missing data of the first residual urine volume. In LOCF 
method, the post-void RUV after the second urination is used to impute missing data 
of the first post-void RUV. 
If secondary catheterization does not occur within 7 days after the removal of the 
urinary catheter, and the post-void RUV by ultrasound after the second urination is 
also missing, handling method: Multiple imputation method is used to impute the 
missing data of the first post-void RUV. 
4) When the data on post-void RUV by ultrasound after the first urination is 
missing, and the situation of secondary catheterization within 7 days after the removal 
of the urinary catheter is also missing. 
If the post-void RUV by ultrasound after the second urination is not missing, 
handling method: The LOCF method is used to impute the missing data of the first 
residual urine volume. If the imputed residual urine volume is greater than 100 ml, the 
primary endpoint is reached (positive), and no imputation of missing data for 
secondary catheterization is performed; if the imputed residual urine volume is less 
than or equal to 100 ml, multiple imputation method is used to impute the missing 
data of secondary catheterization. 
If the post-void RUV by ultrasound after the second urination is also missing, 
handling method: Multiple imputation method is used to impute the missing data of 
the primary endpoint. At this time, the primary endpoint is imputed as a whole 

 
30/ 48 
Version 
2.0
 
 
5 January 2025 
missing data, rather than imputing the RUV and secondary catheterization separately. 
Through the above treatment methods, we will minimize the impact of missing 
data on the research results and ensure the accuracy and reliability of data analysis. 
The handling process of missing data in primary endpoint is shown in Figure 2. 
In the analysis of secondary endpoint and subgroup analysis, we will not perform 
imputation of missing data. 

 
31/ 48 
Version 
2.0
 
 
5 January 2025 
 
Figure 2 Imputation Scheme for Missing Data of the Primary Endpoint 

 
32/ 48 
Version 
2.0
 
 
5 January 2025 
11.4 Efficacy analysis and statistical methods 
11.4.1 Analysis of the primary endpoint 
Categorical variables will be statistically analyzed and described using counts 
(percentages). Without performing multivariate adjustment, the primary endpoints of 
the two groups will be compared in the ITT analysis set, PPA analysis set, and ATA 
analysis set respectively. The absolute risk differences and their 95% confidence 
intervals (95% CI) will be used to describe the differences between the two groups. In 
addition, in the PPA analysis set, the chi - square test or Fisher's exact test will be 
used to analyze the variables related to the primary endpoint. Multivariate logistic 
regression will be used to adjust for factors that may affect the primary endpoint and 
to analyze the independent risk factors influencing the primary endpoint. During this 
process, continuous variables will be converted into categorical variables. The 
variables used for adjustment include the patient grouping (bladder training/direct 
removal), tumor location (the lower border of the tumor is above the peritoneal 
reflection/the lower border of the tumor is below the peritoneal reflection), gender 
(male/female), and age (≤65 years/>65 years) in the PPA dataset. Besides the above - 
mentioned variables, variables with a p - value < 0.1 in the univariate analysis will 
also be included. The adjusted differences between groups will be described using 
odds ratios (OR) and 95% CI. 
11.4.2 Sensitivity Analysis of the Primary Endpoint 
This study will conduct sensitivity analyses on the missing cases of the primary 
endpoint and the positive events of the primary endpoint caused by reasons other than 
urinary retention. The sensitivity analyses for these two scenarios will be 
independently performed within the ITT analysis set. 
11.4.2.1 Sensitivity Analysis of Missing Data 
If the final missing rate of the primary endpoint is less than 5%, no imputation of 

 
33/ 48 
Version 
2.0
 
 
5 January 2025 
the primary endpoint will be carried out in the primary analysis ITT analysis set. If the 
final missing rate of the primary endpoint is ≥ 5%, data imputation will be performed 
according to the imputation scheme for missing data of the primary endpoint shown in 
Figure 2 within the primary analysis ITT analysis set. In the sensitivity analysis, for 
both of the above - mentioned situations, we will impute all missing data as either 
positive events or negative events, and conduct analyses for these two extreme 
scenarios in the ITT population. 
11.4.2.2 Sensitivity Analysis of Positive Primary Endpoint Events Caused 
by Non - urinary Retention Reasons 
In this study, some patients may undergo secondary catheterization due to 
reasons other than urinary retention. Such events may include the following situations: 
1) The patient strongly requests secondary catheterization due to urgent urination or a 
strong sense of fullness, but the volume of urine drained after secondary 
catheterization does not exceed 100 ml; 2) The patient needs secondary 
catheterization due to disease - related factors (such as secondary surgery, urethral 
injury, shock, disturbance of consciousness, intestinal obstruction, bleeding, transfer 
to the ICU, SOFA score ≥2, etc.). In such cases, we still record them as positive 
primary endpoint events, but sensitivity analyses will be conducted for these cases. 
For these patients, if 1) there is data on the post - void residual urine volume after 
the first urination, and the post - void residual urine volume after the first urination is > 
100 ml, the primary endpoint is still considered positive, and no sensitivity analysis 
will be performed. If 2) there is no data on the post - void residual urine volume after 
the first urination, or the post - void residual urine volume after the first urination is ≤ 
100 ml, a sensitivity analysis is required. In the sensitivity analysis, these patients will 
be treated as negative events of the primary endpoint. 
11.4.3 Analysis of secondary endpoints 
In the analysis of secondary endpoints, continuous variables will be described 

 
34/ 48 
Version 
2.0
 
 
5 January 2025 
using mean ± standard deviation or median (interquartile range); categorical variables 
will be described using counts (percentages). Missing values of the secondary 
endpoints will not be imputed, nor will sensitivity analyses be conducted for them. 
11.4.4 Subgroup analysis 
We will explore the differences in the primary endpoints between the two groups 
in different subgroups through subgroup analysis. The subgroups include gender 
(male; female), age (≤65 years old; > 65 years old), the relationship between the lower 
part of the tumor and the peritoneal reflection (above the peritoneal reflection; below 
the peritoneal reflection), as well as other variables that are independently related to 
the primary endpoint in the multivariate analysis. Logistic regression will be used for 
univariate and multivariate analyses, with effect sizes represented by OR and 95% CI, 
and subgroup interaction P-values will be calculated.  
11.5 Exploratory Analysis 
We will conduct an exploratory analysis of the situation of urinary tract infections. 
The main focus is to explore the independent related factors affecting urinary tract 
infections after rectal surgery. The analysis methods include univariate analysis, 
multivariate analysis, as well as subgroup analysis. 
11.6 Interim analysis 
This study does not include an interim analysis 
11.7 Final analysis 
 
We will conduct the primary endpoint analysis of the study after all patients have 
completed their first postoperative month follow-up and will publish the relevant 
research findings. The results of the exploratory analysis will be published separately 
as a post-hoc analysis 

 
35/ 48 
Version 
2.0
 
 
5 January 2025 
11.8 Data Monitoring Committee 
This study establishes a Data and Safety Monitoring Board (DSMB), which is 
composed of senior surgeons, ethicists, and statistical analysts. The members of the 
DSMB are independent of this trial and have no competing interests that could 
influence the trial. The DSMB will receive and review the safety data of this trial. If 
the DSMB believes that the number of adverse events in the trial is biased between 
groups, they will notify the trial steering committee. 
No interim analyses are planned in this study. However, after the study begins, 
the DSMB will assess the study results every six months and may meet earlier for 
assessments. The assessment content includes the recording of primary and secondary 
endpoints, adverse events, and the dropout rate of study samples. Except for the trial 
steering committee, DSMB members must not share confidential information with 
anyone outside the DSMB. 
The interventional methods used in this study (intermittent catheter clamping and 
continuous catheter opening) are common clinical strategies for managing catheters 
after surgical procedures and do not impose additional risks on patients. Therefore, 
this study does not have predefined stopping criteria. However, if the regular 
assessments by the DSMB reveal that the urinary system-related safety indicators due 
to the intervention methods are significantly worse than the current domestic 
standards, the DSMB will submit its recommendations in writing to the trial steering 
committee. This may include requests to modify the trial plan, re-evaluate the quality 
of cases, or even suspend or terminate patient enrollment in the clinical trial. 
12. Data collection and management 
12.1 Case Report Form/Electronic Data Recording 
The Case Report Form (CRF) includes the following primary outcome measures: 
incidence of urinary dysfunction, including bladder residual urine volume after the 

 
36/ 48 
Version 
2.0
 
 
5 January 2025 
first urination, rate of secondary catheterization, time from catheter removal to 
secondary catheterization (hours), method of secondary catheterization (suprapubic 
puncture/urethral catheterization), reasons for secondary catheterization, and urine 
volume drained after secondary catheterization (ml). Secondary outcome measures 
include: urinary tract infection status (white blood cell count in urine, bacterial 
content, and positive/negative urine culture before catheter removal), time to first 
urination after catheter removal (hours), bladder residual urine volume after the first 
urination (milliliters), CRBD grading assessment, bladder training quality 
self-assessment form for the bladder training group, postoperative complications 
within 30 days (incidence of complications, types of complications, and grading of 
complications), and urinary function assessment on the second day after catheter 
removal (ICIQ-SF, IPSS score).Other collected baseline indicators include: gender, 
age, underlying diseases and medical history (hypertension, diabetes, cardiovascular 
disease, cerebrovascular disease, history of pelvic surgery), history of benign prostatic 
hyperplasia in males (confirmed by medical history or imaging), preoperative IPSS 
score, preoperative ICIQ-SF score, preoperative radiotherapy and chemotherapy 
status, preoperative urine routine white blood cell count, preoperative urine routine 
bacterial count, preoperative urine culture results, ASA, BMI, preoperative imaging 
assessment results (preferably rectal MRI), including the distance from the lower edge 
of the tumor to the anal margin, the relationship between the lower edge of the tumor 
and the peritoneal reflection (above/below the peritoneal reflection), clinical T staging, 
clinical N staging, MRF status, EMVI status, surgery duration, surgical procedures, 
including low anterior resection (LAR), intersphincteric resection (ISR), 
abdominoperineal resection (APR), transanal TME (TaTME), Bacon surgery, stoma 
status (ileum/colon, single/double), surgical technique (robotic/laparoscopic), and 
postoperative pathological conditions (pathological T staging, pathological N staging, 
CRM, DRM). See the CRF form for details. 
All patients who meet the inclusion criteria will be registered. For patients who 
are excluded due to the exclusion criteria, the specific reasons for exclusion need to be 
recorded. For the patients who eventually enter the randomization process, their 

 
37/ 48 
Version 
2.0
 
 
5 January 2025 
detailed information will be registered in the database. For patients who deviate from 
the randomized grouping for various reasons and those who deviate from the 
established intervention process during the intervention, the reasons for the deviation 
need to be recorded. All patients after randomization are required to record the 
relevant data completely in accordance with the content of the CRF. 
12.2 Data management 
Data collection will be conducted by the CRC, who will verify and collect 
information on patient enrollment, withdrawal, achievement of primary endpoints, 
and measurement of secondary endpoints daily. Two graduate students will serve as 
data entry personnel. The two graduate students and the CRC will jointly collect 
baseline data. Data entry will be performed using a dual-entry method, with one 
person entering the data and another verifying it. Both paper and electronic versions 
of the CRF will be entered simultaneously. Baseline data will be entered on the day of 
surgery, information related to primary and secondary endpoints will be entered 
within two days of catheter removal, and pathological and other hospitalization 
information must be entered within one week after patient discharge. Complications 
within 30 days after surgery must be entered within 30 days after surgery. To protect 
patient privacy, all patients will be coded and identified using random numbers. These 
random numbers do not include patient initials or date of birth. Investigators will have 
a decoding list that specifies the random numbers of patients in their site's files and 
their patient identification numbers. 
13. Ethics and Morality 
13.1 Ethics committee 
Before the study begins, this trial will obtain ethical approval from the ethics 
committee of our hospital. 

 
38/ 48 
Version 
2.0
 
 
5 January 2025 
13.2 Patient information and informed consent 
Eligible patients should receive personal notification from the treating surgeon 
and be provided with written information related to the trial. Before entering the 
randomization of the study, each patient must provide informed consent in accordance 
with the guidelines of the ethics committee. Patients will have at least 24 hours to 
decide whether to participate in the study and can withdraw from the study at any time 
without reason. 
The informed consent process should be conducted by a physician of the 
attending level or higher within our group. The information provided to patients 
during informed consent includes:1) A statement that the trial involves research;2) A 
full and fair explanation of the procedures to be followed;3) A full explanation of the 
nature, expected duration, and purpose of the research;4) A description of any risks or 
discomforts that the patient can reasonably expect;5) A description of any benefits 
that can be reasonably expected;6) A statement that patient data will be handled with 
care and confidentiality, and the duration of data retention (15 years);7) A statement 
that patient biological materials will be retained for 15 years;8) A statement about 
voluntary participation and withdrawal, indicating that refusal to participate in the 
trial involves no penalty or loss of benefits to which the patient is otherwise entitled, 
and that the patient may stop participating at any time without penalty or loss of 
benefits, in which case the patient will receive standard care of the same quality. 
14. Definition of study completion 
The study is considered complete when all enrolled patients have completed a 
one-month follow-up. 
15. Trial organizational structure 
This study is conducted at a single medical center—The First Hospital of Jilin 

 
39/ 48 
Version 
2.0
 
 
5 January 2025 
University. The trial steering committee members include Quan Wang , Haiyan Hu, 
Jianan Sun, Yuchen Guo , and Tingting He . The Data and Safety Monitoring Board 
(DSMB) is composed of senior surgeons, ethicists, and statistical analysts. Each 
member of the DSMB is independent of this trial and has no competing interests that 
could influence the trial. This clinical trial is funded by the General Surgery Center 
Discipline Special Zone Project of The First Hospital of Jilin University, with the 
project number: 04050520005. 
We did not involve patients or the public in the design of this study or in the 
oversight of its implementation. We also have no plans to share the data from this 
study with the patients who participated in the enrollment. 
16. Confidentiality and data security 
During the study, only data entry personnel and the DSMB are aware of the data 
situation, and others cannot access the database to know specific patient data. DSMB 
members can be aware of patient allocation and trial-related data. The DSMB will 
discuss the relevant results of the data with the trial steering committee members. 
Except for the trial steering committee, DSMB members must not share confidential 
information with anyone outside the DSMB. 
For decisions and recommendations formed through discussions by the DSMB, 
the DSMB will submit these recommendations in writing to the trial steering 
committee. Additionally, the CRC will also receive these recommendations to be 
discussed at the trial steering committee meeting. The content of the meeting needs to 
be stored and secured by the DSMB members after the meeting, so that it can be 
reviewed in comparison with the next report. 
17. Insurance and compensation. 
All enrolled patients have purchased medical commercial insurance in 

 
40/ 48 
Version 
2.0
 
 
5 January 2025 
collaboration with our hospital and an insurance company before surgery. The 
insurance will compensate for surgery-related complications and surgery-related 
deaths. For each patient enrolled in the trial, an enrollment compensation of 100 yuan 
will be provided to enhance the patient's compliance. 
18. Publication statement 
The data will not be published before the collection of primary outcomes is 
completed. We will conduct the primary endpoint analysis of the study after all 
patients have completed their first postoperative month follow-up and will publish the 
relevant research findings. The order of authors will be arranged from highest to 
lowest based on the number of enrolled cases. The results of the exploratory analysis 
will be published separately as a post-hoc analysis after the publication of the results 
of the primary endpoint. 
19.References 
1. 
Williamson ML. Reducing post-catheterization bladder dysfunction by reconditioning. 
Nurs Res. 1982;31(1):28–30.  
2. 
McDonald C, Rees J, Winge K, Newton JL, Burn DJ. Bladder training for urinary 
tract symptoms in Parkinson disease: A randomized controlled trial. Neurology. 2020 
Mar 31;94(13):E1427–33.  
3. 
Rizvi RM, Chughtai NG, Kapadia N. Effects of Bladder Training and Pelvic Floor 
Muscle Training in Female Patients with Overactive Bladder Syndrome: A 
Randomized Controlled Trial. Urol Int. 2018;100(4):420–7.  
4. 
Yoon HS, Song HH, Ro YJ. A comparison of effectiveness of bladder training and 
pelvic muscle exercise on female urinary incontinence. Vol. 40, International Journal 
of Nursing Studies. 2003.  
5. 
Ellahi A, Stewart F, Kidd EA, Griffiths R, Fernandez R, Omar MI. Strategies for the 
removal of short-term indwelling urethral catheters in adults. Cochrane Database Syst 
Rev. 2021 Jun 29;6(6):CD004011.  
6. 
Zhengyong Y, Changxiao H, Shibing Y, Caiwen W. Randomized controlled trial on 
the efficacy of bladder training before removing the indwelling urinary catheter in 
patients with acute urinary retention associated with benign prostatic hyperplasia. 
Scand J Urol. 2014 Aug;48(4):400–4.  
7. 
Fanfani F, Costantini B, Mascilini F, Vizzielli G, Gallotta V, Vigliotta M, et al. Early 

 
41/ 48 
Version 
2.0
 
 
5 January 2025 
postoperative bladder training in patients submitted to radical hysterectomy: is it still 
necessary? A randomized trial. Arch Gynecol Obstet. 2015 Apr;291(4):883–8.  
8. 
谢宇红, 王枭杰, 陈致奋, 池畔, 官国先, 林惠铭, et al. 中低位直肠癌术后男性
患者行膀胱锻炼对膀胱功能恢复影响的前瞻性随机对照研究. 中华胃肠外科杂
志. 2018;21(11):6.  
9. 
Markopoulos G, Kitridis D, Tsikopoulos K, Georgiannos D, Bisbinas I. Bladder 
training prior to urinary catheter removal in total joint arthroplasty. A randomized 
controlled trial. Int J Nurs Stud. 2019 Jan;89:14–7.  
10. 
Muge Catikkas N, Merve Oren M, Ozturk GB. Effect of bladder training on post 
catheterization urinary retention remains to be resolved. Int J Nurs Stud. 2020 
Jan;101:103399.  
11. 
Gaither TW, Patel P, Del Rosario C, Baxter ZC, Pannell S, Dunn M. Predictive Value 
of Voiding Efficiency After Active Void Trial in Men Undergoing BPH Surgery. 
Urology. 2022 Oct;168:169–74.  
12. 
Wong MC, Isaacson K, Morris S. Into the void: a review of postoperative urinary 
retention after minimally invasive gynecologic surgery. Curr Opin Obstet Gynecol. 
2018 Aug;30(4):260–6.  
13. 
Stav K, Rappaport YH, Beberashvili I, Zisman A. Pain Associated With Urethral 
Catheterization Is Reduced in Males by Simultaneous Voiding Maneuver. Urology. 
2017 Apr;102:21–5.  
14. 
Braschinsky M, Zopp I, Kals M, Haldre S, Gross-Paju K. Bladder dysfunction in 
hereditary spastic paraplegia: what to expect? J Neurol Neurosurg Psychiatry. 2010 
Mar;81(3):263–6.  
15. 
Wei B, Zheng Z, Fang J, Xiao J, Han F, Huang M, et al. Effect of Denonvilliers’ 
Fascia Preservation Versus Resection During Laparoscopic Total Mesorectal Excision 
on Postoperative Urogenital Function of Male Rectal Cancer Patients: Initial Results 
of Chinese PUF-01 Randomized Clinical Trial. Ann Surg. 2021 Dec 1;274(6):e473–
80.  
16. 
Sadakari Y, Hisano K, Sada M, Mizuuchi Y, Nagayoshi K, Fujita H, et al. Long-term 
effects of laparoscopic lateral pelvic lymph node dissection on urinary retention in 
rectal cancer. Surg Endosc. 2022 Feb;36(2):999–1007.  
17. 
Lee YH, Lee JE, Ryu DW, Oh YS, Lee KS, Hong SH, et al. Urinary Dysfunctions and 
Post-Void Residual Urine in Typical and Atypical Parkinson Diseases. J Parkinsons 
Dis. 2018;8(1):145–52.  
18. 
Kneist W, Kauff DW, Juhre V, Hoffmann KP, Lang H. Is intraoperative 
neuromonitoring associated with better functional outcome in patients undergoing 
open TME? Results of a case-control study. Eur J Surg Oncol. 2013 Sep;39(9):994–9.  
  
 
 

 
42/ 48 
Version 
2.0
 
 
5 January 2025 
Appendix 1: IPSS Score 
Symptom 
Question 
Score 
Incomplete 
Emptying 
Over the past month, how often have 
you had a sensation of not emptying 
your bladder completely after you 
finished urinating? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Frequency 
Over the past month, how often have 
you had to urinate again less than two 
hours after you finished urinating? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Intermittency 
Over the past month, how often have 
you found you stopped and started 
again several times when you 
urinated? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Urgency 
Over the past month, how difficult 
have you found it to postpone 
urination? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Weak Stream 
Over the past month, how often have 
you had a weak urinary stream? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 

 
43/ 48 
Version 
2.0
 
 
5 January 2025 
3: About half the time 
4: More than half the time 
5: Almost always 
Straining 
Over the past month, how often have 
you had to push or strain to begin 
urination? 
0: None 
1: Less than 1 time in 5 
2: Less than half the time 
3: About half the time 
4: More than half the time 
5: Almost always 
Nocturia 
Over the past month, how many times 
did you typically get up at night to 
urinate? 
0: None 
1: 1 time 
2: 2 times 
3: 3 times 
4: 4 times 
5: 5 or more times 
1.Total Score Calculation: Sum the scores of the above 7 items. The total score ranges 
from 0 to 35. 
①Mild symptoms: 0 - 7 ②Moderate symptoms: 8 - 19 ③Severe symptoms: 20 - 35 
 
 
 

 
44/ 48 
Version 
2.0
 
 
5 January 2025 
Appendix 2: ICIQ-SF Score 
International Consultation on Incontinence Questionnaire - Urinary Incontinence 
Short Form (ICIQ-UI SF) 
1.Please write in your date of birth: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
2.Are you (check one):  Female  Male 
3.How often do you leak urine? Check one box. 
0  Never 
1  About once a week or less often 
2  Two or three times a week 
3  About once a day 
4  Several times a day 
5  All the time 
4.We would like to know how much urine you think leaks. How much urine do you 
usually leak (whether you wear protection or not)? Check one box. 
 0  None 
 2  A small amount 
 4  A moderate amount 
 6  A large amount 
5.Overall, how much does leaking urine interfere with your everyday life? Please 
circle a number between 0 (not at all) and 10 (a great deal) 
  0 1 2 3 4 5 6 7 8 9 10 
Not at all A great deal 
ICIQ score: Sum scores 3 + 4 + 5 
6.When does urine leak? Please check all that apply to you. 
 Never – urine does not leak 
 Leaks before you can get to the bathroom 
 Leaks when you cough or sneeze 
 Leaks when you are asleep 
 Leaks when you are physically active / exercising 
 Leaks when you have finished urinating and are dressed 

 
45/ 48 
Version 
2.0
 
 
5 January 2025 
 Leaks for no obvious reason 
 Leaks all the time 
 
The grading of urinary incontinence: 
- Total score of 0 - 5: No urinary incontinence or mild urinary incontinence. 
- Total score of 6 - 10: Moderate urinary incontinence. 
- Total score of 11 and above: Severe urinary incontinence. 
 
 
 

 
46/ 48 
Version 
2.0
 
 
5 January 2025 
Appendix 3: CRBD Grading Assessment 
Grading 
Symptoms 
Grade 0 
No discomfort at all 
Grade 1 
Only informed of urethral discomfort when asked and it is 
tolerable. 
Grade 2 
The patient actively informed of urgency, dysuria and lower 
abdominal distension, but without behavioral response 
Grade 3 
The patient actively informed of urgency, dysuria and lower 
abdominal distension, accompanied by behavioral responses 
(such as severe restlessness, limb movement, attempting to 
remove the catheter), requiring medical staff to restrain and 
multiple caregivers to watch. 
 
 
 
 
 
 

 
47/ 48 
Version 
2.0
 
 
5 January 2025 
Appendix 4: Bladder Training Quality Self-Assessment Form 
1.Total number of times the catheter was clamped? 
2.Did you feel the urge to urinate each time during the clamping training? 
□ Every time； 
□ More than half of the times; 
□ Less than half of the times; 
□ Never 
3.Were you able to hold for 3 hours before releasing the catheter? 
□ Every time； 
□ More than half of the times; 
□ Less than half of the times; 
□ Never 
4.Did you cooperate with the urination action after releasing the catheter? 
□ Every time； 
□ More than half of the times; 
□ Less than half of the times; 
□ Never 
 
 
 

 
48/ 48 
Version 
2.0
 
 
5 January 2025 
Appendix 5: Postoperative Complications Clavien-Dindo System Grading. 
Grading 
Definition 
I 
Postoperative complications that do not require drug, 
surgical, endoscopic, or radiological intervention, but include 
drug therapy such as anti-emetics, antipyretics, analgesics, 
diuretics, electrolytes, physiotherapy, and also include incisional 
infections that are opened at the bedside; 
II 
Requires drug therapy, excluding patients who only received 
Grade I medication, incisional infections requiring antibiotic 
treatment, and includes blood transfusions and total parenteral 
nutrition 
III 
Requires surgical, endoscopic, or radiological intervention 
 
III
a 
Does not require general anesthesia 
III
b 
Requires general anesthesia 
IV 
Life-threatening complications (including central nervous 
system complications) requiring IC (intermediate care) or ICU 
management 
 
IV
a 
Organ failure (including dialysis) 
IV
b 
Multi-organ failure 
V 
Death 
 
 
 
 

瀉濸瀅瀆濼瀂瀁 1.1.1
瀉濸瀅瀆濼瀂瀁 1.1.2
2.2.2 S濸濶瀂瀁濷濴瀅y 瀆瀇瀈濷y 
濸瀁濷瀃瀂濼瀁瀇瀆 濴瀁濷 濷濸濹濼瀁濼瀇濼瀂瀁瀆.
T濻濸 瀆濸濶瀂瀁濷濴瀅y 瀆瀇瀈濷y 濸瀁濷瀃瀂濼瀁瀇 濼瀆 濴濷濷濸濷 瀊濼瀇濻 6) I瀁濶濼濷濸瀁濶濸 瀂濹 
瀅濸瀆濼濷瀈濴濿 瀈瀅濼瀁濸 瀉瀂濿瀈瀀濸 濺瀅濸濴瀇濸瀅 瀇濻濴瀁 200 瀀濼濿濿濼濿濼瀇濸瀅瀆 濴濹瀇濸瀅 瀇濻濸 濹濼瀅瀆瀇 
瀈瀅濼瀁濴瀇濼瀂瀁.
5.1.1 M濸瀇濻瀂濷瀆 濹瀂瀅 
G濸瀁濸瀅濴瀇濼瀁濺 R濴瀁濷瀂瀀 
S濸瀄瀈濸瀁濶濸瀆
T濻濸 瀅濴瀁濷瀂瀀濿y 濴瀆瀆濼濺瀁濸濷 瀇濼瀀濸 濼瀆 瀂瀁 瀇濻濸 濷濴y 瀊濻濸瀁 瀇濻濸 瀃濴瀇濼濸瀁瀇 
瀅濸瀇瀈瀅瀁瀆 瀇瀂 瀇濻濸 瀊濴瀅濷 濴濹瀇濸瀅 瀇濻濸 瀂瀃濸瀅濴瀇濼瀂瀁. 
R濴瀁濷瀂瀀 濴瀆瀆濼濺瀁瀀濸瀁瀇 瀊濼濿濿 瀇濴濾濸 瀃濿濴濶濸 濵濸瀇瀊濸濸瀁 6:00 濴瀀 濴瀁濷 7:00 濴瀀 
瀂瀁 瀇濻濸 濹濼瀅瀆瀇 瀃瀂瀆瀇瀂瀃濸瀅濴瀇濼瀉濸 濷濴y, 濵濸濹瀂瀅濸 瀇濻濸 濼瀁瀇濸瀅瀉濸瀁瀇濼瀂瀁 濼瀆 濶濴瀅瀅濼濸濷 
瀂瀈瀇. 
15. T瀅濼濴濿 瀂瀅濺濴瀁濼z濴瀇濼瀂瀁濴濿 
瀆瀇瀅瀈濶瀇瀈瀅濸
T濻濼瀆 瀆瀇瀈濷y 濻濴瀆 瀁瀂 瀅濸瀆濸濴瀅濶濻 濹瀈瀁濷濼瀁濺 瀆瀈瀃瀃瀂瀅瀇.
A濷濷 濴 濷濸瀆濶瀅濼瀃瀇濼瀂瀁 瀂濹 瀊濻濸瀇濻濸瀅 瀃濴瀇濼濸瀁瀇瀆 濴瀁濷 瀇濻濸 瀃瀈濵濿濼濶 瀃濴瀅瀇濼濶濼瀃濴瀇濸濷 
濼瀁 瀇濻濸 濷濸瀆濼濺瀁 瀂濹 瀇濻濼瀆 瀃瀅瀂濽濸濶瀇 濴瀁濷 瀇濻濸 瀆瀈瀃濸瀅瀉濼瀆濼瀂瀁 瀂濹 瀃瀅瀂濽濸濶瀇 
濼瀀瀃濿濸瀀濸瀁瀇濴瀇濼瀂瀁.
A濷濷 瀃瀅瀂濽濸濶瀇 濹瀈瀁濷濼瀁濺 瀆瀇濴瀇濸瀀濸瀁瀇瀆.

瀆濸濶瀇濼瀂瀁
瀉濸瀅瀆濼瀂瀁 1.1.2
瀉濸瀅瀆濼瀂瀁 2.0
R濸濴瀆瀂瀁瀆 濹瀂瀅 R濸瀉濼瀆濼瀂瀁
2.2.1 P瀅濼瀀濴瀅瀌 S瀇瀈濷瀌 E瀁濷瀃瀂濼瀁瀇 濴瀁濷 
D濸濹濼瀁濼瀇濼瀂瀁
I瀁 瀇濻濸 濴瀆瀆濸瀆瀆瀀濸瀁瀇 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇, 濼濹 濴 瀃濴瀇濼濸瀁瀇 
瀈瀁濷濸瀅濺瀂濸瀆 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濵瀈瀇 濷瀂濸瀆 瀁瀂瀇 瀀濸濸瀇 瀇濻濸 
濶瀅濼瀇濸瀅濼濴 濹瀂瀅 瀊濼瀇濻濷瀅濴瀊濴濿, 濴瀁濷 濼濹 瀇濻濸 瀈瀅濼瀁濸 瀉瀂濿瀈瀀濸 濷瀅濴濼瀁濸濷 濴濹瀇濸瀅 
瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濼瀆 濿濸瀆瀆 瀇濻濴瀁 100 瀀濿, 瀆瀈濶濻 瀃濴瀇濼濸瀁瀇瀆 瀊濼濿濿 
瀁瀂瀇 濵濸 濷濸濹濼瀁濸濷 濴瀆 濻濴瀉濼瀁濺 瀈瀅濼瀁濴瀅瀌 濷瀌瀆濹瀈瀁濶瀇濼瀂瀁.
I瀁 瀇濻濸 濷濸瀇濸瀅瀀濼瀁濴瀇濼瀂瀁 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇, 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 
瀈瀁濷濸瀅濺瀂 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濹瀂瀅 瀅濸濴瀆瀂瀁瀆 瀂瀇濻濸瀅 瀇濻濴瀁 
瀈瀅濼瀁濴瀅瀌 瀅濸瀇濸瀁瀇濼瀂瀁 瀊濼濿濿 濴濿瀆瀂 濵濸 瀅濸濶瀂瀅濷濸濷 濴瀆 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇 
濸瀉濸瀁瀇瀆, 濵瀈瀇 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濼瀆 瀆濻濴濿濿 濵濸 濶瀂瀁濷瀈濶瀇濸濷 瀂瀁 瀇濻濸瀆濸 
瀃濴瀇濼濸瀁瀇瀆 濼瀁 瀇濻濸 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濼瀆. T濻濸 瀆瀃濸濶濼濹濼濶 濴瀁濴濿瀌瀆濼瀆 瀀濸瀇濻瀂濷 
濼瀆 濷濸瀆濶瀅濼濵濸濷 濼瀁 瀇濻濸 瀆濸濶瀇濼瀂瀁 瀂瀁 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 
濸瀁濷瀃瀂濼瀁瀇 濼瀁 瀇濻濸 瀆瀇濴瀇濼瀆瀇濼濶濴濿 濴瀁濴濿瀌瀆濼瀆. S瀈濶濻 濸瀉濸瀁瀇瀆 瀀濴瀌 濼瀁濶濿瀈濷濸 瀇濻濸 
濹瀂濿濿瀂瀊濼瀁濺 瀆濶濸瀁濴瀅濼瀂瀆: 
1) T濻濸 瀃濴瀇濼濸瀁瀇 瀅濸瀄瀈濸瀆瀇瀆 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濷瀈濸 瀇瀂 
瀈瀅濺濸瀁瀇 瀈瀅濼瀁濴瀇濼瀂瀁 瀂瀅 濼瀁瀇濸瀁瀆濸 濵濿瀂濴瀇濼瀁濺, 濵瀈瀇 瀇濻濸 瀈瀅濼瀁濸 瀉瀂濿瀈瀀濸 
瀊濼瀇濻濷瀅濴瀊瀁 濴濹瀇濸瀅 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濷瀂濸瀆 瀁瀂瀇 濸瀋濶濸濸濷 100 
瀀濿; 
2) T濻濸 瀃濴瀇濼濸瀁瀇 瀅濸瀄瀈濼瀅濸瀆 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濷瀈濸 瀇瀂 
濷濼瀆濸濴瀆濸-瀅濸濿濴瀇濸濷 濹濴濶瀇瀂瀅瀆 (瀆瀈濶濻 濴瀆 瀆濸濶瀂瀁濷濴瀅瀌 瀆瀈瀅濺濸瀅瀌, 瀈瀅濸瀇濻瀅濴濿 
濼瀁濽瀈瀅瀌, 瀆濻瀂濶濾, 濴濿瀇濸瀅濸濷 濶瀂瀁瀆濶濼瀂瀈瀆瀁濸瀆瀆, 濼瀁瀇濸瀆瀇濼瀁濴濿 瀂濵瀆瀇瀅瀈濶瀇濼瀂瀁, 
濻濸瀀瀂瀅瀅濻濴濺濸, 瀇瀅濴瀁瀆濹濸瀅 瀇瀂 ICU, SOFA 瀆濶瀂瀅濸 ≥2, 濸瀇濶.).
I瀁 瀇濻濸 瀂瀅濼濺濼瀁濴濿 瀃瀅瀂瀇瀂濶瀂濿, 瀇濻濼瀆 濶濴瀇濸濺瀂瀅瀌 瀂濹 瀃濴瀇濼濸瀁瀇瀆 瀀濼濺濻瀇 濼瀁濶濿瀈濷濸 
瀇濻瀂瀆濸 瀊濼瀇濻 瀈瀅濼瀁濴瀅瀌 濷濼瀆濶瀂瀀濹瀂瀅瀇 瀊濻瀂 瀉瀂濼濷 瀀瀈濿瀇濼瀃濿濸 瀇濼瀀濸瀆 瀂瀅 瀇濻瀂瀆濸 
瀊濻瀂 瀅濸瀄瀈濼瀅濸 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濷瀈濸 瀇瀂 瀀濸濷濼濶濴濿 
濶瀂瀁濷濼瀇濼瀂瀁瀆. I瀁 瀇濻濸 瀂瀅濼濺濼瀁濴濿 瀃瀅瀂瀇瀂濶瀂濿, 濶濿濴瀆瀆濼濹瀌濼瀁濺 瀇濻濸瀆濸 瀃濴瀇濼濸瀁瀇瀆 濴瀆 
瀁濸濺濴瀇濼瀉濸 濸瀉濸瀁瀇瀆 瀀濴瀌 濻濴瀉濸 濿濸濷 瀇瀂 濴瀁 瀈瀁濷濸瀅濸瀆瀇濼瀀濴瀇濼瀂瀁 瀂濹 瀃瀂瀆濼瀇濼瀉濸 
濸瀉濸瀁瀇瀆. I瀁 瀇濻濸 瀅濸瀉濼瀆濸濷 瀃瀅瀂瀇瀂濶瀂濿, 瀇濻濸瀆濸 濸瀉濸瀁瀇瀆 濴瀅濸 濶濿濴瀆瀆濼濹濼濸濷 濴瀆 
瀃瀂瀆濼瀇濼瀉濸 濸瀉濸瀁瀇瀆, 濴瀁濷 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濼瀆 濼瀆 瀃濸瀅濹瀂瀅瀀濸濷 瀇瀂 濸瀁濴濵濿濸 
濴 瀀瀂瀅濸 濶瀂瀀瀃瀅濸濻濸瀁瀆濼瀉濸 濴瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇.
4.1 I瀁濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴
2) P濴瀇濼濸瀁瀇瀆 瀊濼瀇濻 瀇瀈瀀瀂瀅瀆 濿瀂濶濴瀇濸濷 濵濸濿瀂瀊 瀇濻濸 瀅濸濶瀇瀂瀆濼濺瀀瀂濼濷 
濽瀈瀁濶瀇濼瀂瀁, 濴瀆 濷濸瀇濸瀅瀀濼瀁濸濷 濵瀌 瀃瀅濸瀂瀃濸瀅濴瀇濼瀉濸 濶瀂瀀瀃瀈瀇濸濷 
瀇瀂瀀瀂濺瀅濴瀃濻瀌 (CT) 瀂瀅 瀅濸濶瀇濴濿 瀀濴濺瀁濸瀇濼濶 瀅濸瀆瀂瀁濴瀁濶濸 濼瀀濴濺濼瀁濺 (MRI).
P瀅濸瀂瀃濸瀅濴瀇濼瀉濸 濶瀂濿瀂瀁 CT 瀂瀅 瀅濸濶瀇濴濿 MR 濶瀂瀁濹濼瀅瀀瀆 瀇濻濴瀇 瀇濻濸 濿瀂瀊濸瀅 
濸濷濺濸 瀂濹 瀇濻濸 瀇瀈瀀瀂瀅 濼瀆 濿瀂濶濴瀇濸濷 濼瀁 瀇濻濸 瀅濸濶瀇瀈瀀 (濼瀁濶濿瀈濷濼瀁濺 瀇濻濸 瀅濸濶瀇濴濿 
濴瀁濷 濴瀁濴濿 濶濴瀁濴濿 瀅濸濺濼瀂瀁瀆) 濵濸濿瀂瀊 瀇濻濸 瀅濸濶瀇瀂瀆濼濺瀀瀂濼濷 濽瀈瀁濶瀇濼瀂瀁 (12 
濶瀀 濹瀅瀂瀀 瀇濻濸 濴瀁濴濿 瀉濸瀅濺濸);
T濻濸 濷濸濹濼瀁濼瀇濼瀂瀁 瀂濹 瀇濻濸 瀅濸濶瀇瀂瀆濼濺瀀瀂濼濷 濽瀈瀁濶瀇濼瀂瀁 瀀濴瀌 瀉濴瀅瀌 濴濶瀅瀂瀆瀆 
濷濼濹濹濸瀅濸瀁瀇 濿濼瀇濸瀅濴瀇瀈瀅濸瀆. T濻濸 瀇瀅濼濴濿 瀇濸濴瀀 瀂濹 瀂瀈瀅 濶濸瀁瀇濸瀅 濷濸濹濼瀁濸瀆 瀇濻濸 
濿瀂瀊濸瀅 濵瀂瀈瀁濷濴瀅瀌 瀂濹 瀇濻濸 瀅濸濶瀇瀂瀆濼濺瀀瀂濼濷 濽瀈瀁濶瀇濼瀂瀁 濴瀆 12 濶瀀 濹瀅瀂瀀 
瀇濻濸 濴瀁瀈瀆. I瀁 瀇濻濸 瀅濸瀉濼瀆濸濷 瀃瀅瀂瀇瀂濶瀂濿, 瀇濻濸 瀆瀃濸濶濼濹濼濶 濿濸瀁濺瀇濻 瀅濴瀁濺濸 濼瀆 
瀀瀂瀅濸 濶濿濸濴瀅濿瀌 瀀濴瀅濾濸濷 瀇瀂 濴瀉瀂濼濷 濷濼瀆濶瀅濸瀃濴瀁濶濼濸瀆 濼瀁 瀅濸濴濷濼瀁濺 濴瀁濷 
瀈瀁濷濸瀅瀆瀇濴瀁濷濼瀁濺 濵瀌 瀂瀇濻濸瀅 瀅濸瀆濸濴瀅濶濻濸瀅瀆.
4.3 W濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴
4.3 W濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴.
A濹瀇濸瀅 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁, 瀃濴瀇濼濸瀁瀇瀆 瀊濼濿濿 濵濸 瀊濼瀇濻濷瀅濴瀊瀁 濹瀅瀂瀀 瀇濻濸 瀇瀅濼濴濿 濼濹 
濴瀁瀌 瀂濹 瀇濻濸 濹瀂濿濿瀂瀊濼瀁濺 瀆濼瀇瀈濴瀇濼瀂瀁瀆 瀂濶濶瀈瀅:
1) I瀁濴濵濼濿濼瀇瀌 瀇瀂 瀅濸瀀瀂瀉濸 瀇濻濸 瀈瀅濼瀁濴瀅瀌 濶濴瀇濻濸瀇濸瀅 瀊濼瀇濻濼瀁 5 濷濴瀌瀆 
瀃瀂瀆瀇瀂瀃濸瀅濴瀇濼瀉濸濿瀌 濷瀈濸 瀇瀂 瀉濴瀅濼瀂瀈瀆 瀅濸濴瀆瀂瀁瀆 (濸.濺., 濼瀀瀃濴濼瀅濸濷 
濶瀂瀁瀆濶濼瀂瀈瀆瀁濸瀆瀆, 瀇瀅濴瀁瀆濹濸瀅 瀇瀂 瀇濻濸 濼瀁瀇濸瀁瀆濼瀉濸 濶濴瀅濸 瀈瀁濼瀇 (ICU), 
S濸瀄瀈濸瀁瀇濼濴濿 O瀅濺濴瀁 F濴濼濿瀈瀅濸 A瀆瀆濸瀆瀆瀀濸瀁瀇 (SOFA) 瀆濶瀂瀅濸 ≥2, 濸瀇濶.).
2) S濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 瀊濴瀆 瀃濸瀅濹瀂瀅瀀濸濷 濹瀂瀅 瀅濸濴瀆瀂瀁瀆 瀂瀇濻濸瀅 
瀇濻濴瀁 瀈瀅濼瀁濴瀅瀌 瀅濸瀇濸瀁瀇濼瀂瀁 (濸.濺., 瀆濸濶瀂瀁濷濴瀅瀌 瀆瀈瀅濺濸瀅瀌, 瀆濻瀂濶濾, 瀅濸濶瀇濴濿 
濵濿濴濷濷濸瀅 濿濸濴濾濴濺濸, 瀈瀅濸瀇濸瀅濴濿 濿濸濴濾濴濺濸, 瀂瀅 瀈瀅濸瀇濻瀅濴濿 濼瀁濽瀈瀅瀌).
3) P濴瀇濼濸瀁瀇 瀅濸瀄瀈濸瀆瀇瀆 瀇瀂 瀊濼瀇濻濷瀅濴瀊 濹瀅瀂瀀 瀇濻濸 瀆瀇瀈濷瀌 濴瀇 濴瀁瀌 瀇濼瀀濸 
濷瀈瀅濼瀁濺 瀇濻濸 濸瀁瀇濼瀅濸 瀆瀇瀈濷瀌 瀃瀅瀂濶濸瀆瀆.
4) S濸濿濸濶瀇濼瀉濸 α1-濴濷瀅濸瀁濸瀅濺濼濶 瀅濸濶濸瀃瀇瀂瀅 濵濿瀂濶濾濸瀅 濼瀆 瀈瀆濸濷 濷瀈瀅濼瀁濺 瀇濻濸 
濹濼瀅瀆瀇 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 瀂濹 瀇濻濸 瀃濴瀇濼濸瀁瀇 濷瀈濸 瀇瀂 瀀濸濷濼濶濴濿 瀁濸濶濸瀆瀆濼瀇瀌.
D濸濿濸瀇濸 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴.
I瀁 瀇濻濼瀆 瀆瀇瀈濷瀌, 瀇濻濸 瀀ITT 濴瀁濴濿瀌瀆濼瀆 濼瀁 瀇濻濸 瀂瀅濼濺濼瀁濴濿 瀃瀅瀂瀇瀂濶瀂濿 
濸瀋濶濿瀈濷濸濷 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 瀀濸瀇 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴, 瀊濻濼濶濻 瀀濴瀌 濻濴瀉濸 
濷濼瀆瀅瀈瀃瀇濸濷 瀇濻濸 瀇瀅濼濴濿'瀆 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 濴瀁濷 濼瀁瀇瀅瀂濷瀈濶濸濷 瀆濸濿濸濶瀇濼瀂瀁 
濵濼濴瀆. T濻濸瀅濸濹瀂瀅濸, 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇 濼瀁 瀇濻濸 瀅濸瀉濼瀆濸濷 瀃瀅瀂瀇瀂濶瀂濿 
濻濴瀆 濵濸濸瀁 濶濻濴瀁濺濸濷 瀇瀂 瀇濻濸 ITT (I瀁瀇濸瀁瀇濼瀂瀁-瀇瀂-T瀅濸濴瀇) 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇, 
瀀濸濴瀁濼瀁濺 濴濿濿 瀅濴瀁濷瀂瀀濼瀍濸濷 瀃濴瀇濼濸瀁瀇瀆 濴瀅濸 濼瀁濶濿瀈濷濸濷 濼瀁 瀇濻濸 濴瀁濴濿瀌瀆濼瀆. 
T濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴 濻濴瀉濸 濵濸濸瀁 瀅濸瀀瀂瀉濸濷, 濴瀁濷 濶濴瀆濸瀆 
瀃瀅濸瀉濼瀂瀈瀆濿瀌 濶瀂瀉濸瀅濸濷 濵瀌 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴 瀊濼濿濿 濵濸 濼瀁濶濿瀈濷濸濷 濼瀁 
瀇濻濸 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濼瀆.
5. S瀇瀈濷瀌 瀇瀅濸濴瀇瀀濸瀁瀇 濺瀅瀂瀈瀃瀆
…… I濹 瀇濻濸 SOFA 瀆濶瀂瀅濸 濼瀆 2 瀂瀅 濻濼濺濻濸瀅, 瀇濻濸 濷瀈瀅濴瀇濼瀂瀁 瀂濹 濶濴瀇濻濸瀇濸瀅 
瀃濿濴濶濸瀀濸瀁瀇 瀆濻瀂瀈濿濷 濵濸 濸瀋瀇濸瀁濷濸濷. I濹 瀇濻濸 濶濴瀇濻濸瀇濸瀅 瀆瀇濼濿濿 濶濴瀁瀁瀂瀇 濵濸 
瀅濸瀀瀂瀉濸濷 濵瀌 瀇濻濸 濹濼濹瀇濻 濷濴瀌 濷瀈濸 瀇瀂 濴 SOFA 瀆濶瀂瀅濸 瀂濹 2 瀂瀅 濻濼濺濻濸瀅, 
瀇濻濸 瀃濴瀇濼濸瀁瀇 瀊濼濿濿 濵濸 濸瀋濶濿瀈濷濸濷 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 
濶瀅濼瀇濸瀅濼濴. ……
D濸濿濸瀇濸“. I濹 瀇濻濸 濶濴瀇濻濸瀇濸瀅 瀆瀇濼濿濿 濶濴瀁瀁瀂瀇 濵濸 瀅濸瀀瀂瀉濸濷 濵瀌 瀇濻濸 濹濼濹瀇濻 濷濴瀌 
濷瀈濸 瀇瀂 濴 SOFA 瀆濶瀂瀅濸 瀂濹 2 瀂瀅 濻濼濺濻濸瀅, 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀊濼濿濿 濵濸 
濸瀋濶濿瀈濷濸濷 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴.”
T濻濸 瀅濸瀉濼瀆濸濷 瀃瀅瀂瀇瀂濶瀂濿 濻濴瀆 濷濸濿濸瀇濸濷 瀇濻濸 濸瀋濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴, 瀆瀂 瀇濻濸 
濷濸瀆濶瀅濼瀃瀇濼瀂瀁 "濼濹 瀇濻濸 瀈瀅濼瀁濴瀅瀌 濶濴瀇濻濸瀇濸瀅 濶濴瀁瀁瀂瀇 濵濸 瀅濸瀀瀂瀉濸濷 濷瀈濸 瀇瀂 濴 
SOFA 瀆濶瀂瀅濸 ≥2 瀃瀂濼瀁瀇瀆 濵濸瀌瀂瀁濷 濷濴瀌 5, 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀊濼濿濿 濵濸 
濸瀋濶濿瀈濷濸濷 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴" 濻濴瀆 濵濸濸瀁 
瀅濸瀀瀂瀉濸濷 濼瀁 瀇濻濸 瀁濸瀊 瀉濸瀅瀆濼瀂瀁.
5.1.1 M濸瀇濻瀂濷瀆 濹瀂瀅 G濸瀁濸瀅濴瀇濼瀁濺 
R濴瀁濷瀂瀀 S濸瀄瀈濸瀁濶濸瀆
R濴瀁濷瀂瀀 濴瀆瀆濼濺瀁瀀濸瀁瀇 瀊濼濿濿 瀇濴濾濸 瀃濿濴濶濸 濵濸瀇瀊濸濸瀁 6:00 濴瀀 濴瀁濷 7:00 
濴瀀 瀂瀁 瀇濻濸 濹濼瀅瀆瀇 瀃瀂瀆瀇瀂瀃濸瀅濴瀇濼瀉濸 濷濴瀌, 濵濸濹瀂瀅濸 瀇濻濸 濼瀁瀇濸瀅瀉濸瀁瀇濼瀂瀁 濼瀆 
濶濴瀅瀅濼濸濷 瀂瀈瀇. T濻濸 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 瀊濼濿濿 濵濸 濷濼瀆瀇瀅濼濵瀈瀇濸濷 瀇瀂 瀇濻濸 
濴瀆瀆濼濺瀁濸濷 瀁瀈瀅瀆濸 瀉濼濴 濴瀁 濸瀁瀉濸濿瀂瀃濸, 濴瀁濷 瀇濻濸 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 瀊濼濿濿 
濵濸 濶瀂瀁濷瀈濶瀇濸濷 濵瀌 瀇濻濸 濴瀆瀆濼濺瀁濸濷 瀁瀈瀅瀆濸.
A 瀅濴瀁濷瀂瀀 瀁瀈瀀濵濸瀅 瀇濴濵濿濸 瀀濴瀁濴濺濸瀅 (RNTM) (Y濴瀁濻瀈濴 W瀈) 濹瀅瀂瀀 
瀇濻濸 R濸瀆濸濴瀅濶濻 C濸瀁瀇瀅濸 瀂濹 C濿濼瀁濼濶濴濿 E瀃濼濷濸瀀濼瀂濿瀂濺瀌 (RCCE) 濴瀇 J濼濿濼瀁 
U瀁濼瀉濸瀅瀆濼瀇瀌 F濼瀅瀆瀇 H瀂瀆瀃濼瀇濴濿 濺濸瀁濸瀅濴瀇濸瀆 濴瀁濷 瀃瀅濸瀆濸瀅瀉濸瀆 瀇濻濸 瀅濴瀁濷瀂瀀 
瀁瀈瀀濵濸瀅 瀇濴濵濿濸 濴瀁濷 濴濿濿瀂濶濴瀇濸瀆 瀇濻濸 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁. T濻濸 
RNTM 濼瀆 濼瀁濷濸瀃濸瀁濷濸瀁瀇 瀂濹 瀂瀇濻濸瀅 瀅濸瀆濸濴瀅濶濻濸瀅瀆 濼瀁 瀇濻濼瀆 瀇瀅濼濴濿.
瀊濸 瀀瀂瀉濸 瀇濻濼瀆 濷濸瀆濶瀅濼瀃瀇濼瀂瀁 濼瀁 瀉濸瀅瀆濼瀂瀁 1.1.2 瀇瀂 瀆濸濶瀇濼瀂瀁 "5.1.2 
R濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 濶瀂瀁濶濸濴濿瀀濸瀁瀇" 濼瀁 瀉濸瀅瀆濼瀂瀁 2.0, 濴瀁濷 瀃瀅瀂瀉濼濷濸 濴 
濷濸瀇濴濼濿濸濷 濷濸瀆濶瀅濼瀃瀇濼瀂瀁 瀂濹 瀊濻瀂 濺濸瀁濸瀅濴瀇濸濷 瀇濻濸 瀅濴瀁濷瀂瀀 瀁瀈瀀濵濸瀅 
瀇濴濵濿濸 瀇瀂 濸瀁瀆瀈瀅濸 瀇濻濸 瀇瀅濴瀁瀆瀃濴瀅濸瀁濶瀌 瀂濹 瀇濻濸 瀃瀅瀂瀇瀂濶瀂濿.
5.1.2 R濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 濶瀂瀁濶濸濴濿瀀濸瀁瀇.
A濹瀇濸瀅 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁, 瀇濻濸 濺瀅瀂瀈瀃 濴瀆瀆濼濺瀁瀀濸瀁瀇 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 瀊濼濿濿 濵濸 
瀃瀅濼瀁瀇濸濷 瀂瀁 濴 瀆濿濼瀃 瀂濹 瀃濴瀃濸瀅 濴瀁濷 瀃濿濴濶濸濷 濼瀁瀇瀂 濴瀁 瀂瀃濴瀄瀈濸 濸瀁瀉濸濿瀂瀃濸. 
B濸濹瀂瀅濸 8:00 濴瀀 瀂瀁 瀇濻濸 瀆濸濶瀂瀁濷 瀃瀂瀆瀇瀂瀃濸瀅濴瀇濼瀉濸 濷濴瀌, 瀇濻濸 濸瀁瀉濸濿瀂瀃濸 
濶瀂瀁瀇濴濼瀁濼瀁濺 瀇濻濸 濺瀅瀂瀈瀃 濴瀆瀆濼濺瀁瀀濸瀁瀇 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 瀊濼濿濿 濵濸 濺濼瀉濸瀁 瀇瀂 
瀇濻濸 濴瀆瀆濼濺瀁濸濷 瀁瀈瀅瀆濸, 瀊濻瀂 瀊濼濿濿 濶瀂瀁濷瀈濶瀇 瀇濻濸 濶濴瀇濻濸瀇濸瀅 瀇瀅濴濼瀁濼瀁濺.
A濹瀇濸瀅 瀇濻濸 瀅濴瀁濷瀂瀀 瀁瀈瀀濵濸瀅 瀇濴濵濿濸 濼瀆 濺濸瀁濸瀅濴瀇濸濷 瀇濻瀅瀂瀈濺濻 R 濵瀌 
RNTM, 瀇濻濸 瀅濴瀁濷瀂瀀 濴濿濿瀂濶濴瀇濼瀂瀁 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 瀊濼濿濿 濵濸 瀃瀅濼瀁瀇濸濷 瀂瀁 
瀃濴瀃濸瀅 瀆瀇瀅濼瀃瀆 濴瀁濷 瀃濿濴濶濸濷 濼瀁瀇瀂 瀂瀃濴瀄瀈濸 濸瀁瀉濸濿瀂瀃濸瀆. T濻濸 瀅濴瀁濷瀂瀀 
瀁瀈瀀濵濸瀅 瀇濴濵濿濸 濴瀁濷 瀅濴瀁濷瀂瀀 濴濿濿瀂濶濴瀇濼瀂瀁 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 瀊濼濿濿 濵濸 濾濸瀃瀇 
濵瀌 瀇濻濸 RNTM 濹瀅瀂瀀 瀇濻濸 RCCE. A濹瀇濸瀅 濶濿濼瀁濼濶濴濿 濷瀂濶瀇瀂瀅瀆 濴瀁濷 濵濸濷瀆濼濷濸 
瀁瀈瀅瀆濸瀆 濶瀂瀀瀃濿濸瀇濸 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀆濶瀅濸濸瀁濼瀁濺 濴瀁濷 濷濸瀇濸瀅瀀濼瀁濸 瀇濻濴瀇 濴 
瀃濴瀇濼濸瀁瀇 瀀濸濸瀇瀆 瀇濻濸 濼瀁濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴 濹瀂瀅 濸瀁瀅瀂濿濿瀀濸瀁瀇, 瀅濴瀁濷瀂瀀 
濴濿濿瀂濶濴瀇濼瀂瀁 濶濴瀁 濵濸 濶瀂瀁濷瀈濶瀇濸濷. T濻濸 瀅濴瀁濷瀂瀀 濴濿濿瀂濶濴瀇濼瀂瀁 瀊濼濿濿 瀇濴濾濸 
瀃濿濴濶濸 濵濸瀇瀊濸濸瀁 6:00 濴.瀀. 濴瀁濷 7:00 濴.瀀. 瀂瀁 瀇濻濸 濹濼瀅瀆瀇 濷濴瀌 濴濹瀇濸瀅 瀇濻濸 
瀃濴瀇濼濸瀁瀇'瀆 瀆瀈瀅濺濸瀅瀌, 濵濸濹瀂瀅濸 瀇濻濸 濼瀁瀇濸瀅瀉濸瀁瀇濼瀂瀁 瀃瀅瀂濶濸濷瀈瀅濸. C濿濼瀁濼濶濴濿 
濷瀂濶瀇瀂瀅瀆 濴瀁濷 濵濸濷瀆濼濷濸 瀁瀈瀅瀆濸瀆 瀊濼濿濿 瀆瀈濵瀀濼瀇 濴瀁 濸瀁瀅瀂濿濿瀀濸瀁瀇 
濴瀃瀃濿濼濶濴瀇濼瀂瀁 瀇瀂 瀇濻濸 RNTM 濴瀁濷 瀃瀅瀂瀉濼濷濸 瀇濻濸 瀃濴瀇濼濸瀁瀇'瀆 濺濸瀁濷濸瀅 
濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 濴瀁濷 瀊濻濸瀇濻濸瀅 瀇濻濸瀌 濻濴瀉濸 瀈瀁濷濸瀅濺瀂瀁濸 濴瀁 APR 瀆瀈瀅濺濸瀅瀌. 
B濴瀆濸濷 瀂瀁 瀇濻濸 瀆瀇瀅濴瀇濼濹濼濶濴瀇濼瀂瀁 濶瀂瀅瀅濸瀆瀃瀂瀁濷濼瀁濺 瀇瀂 瀇濻濸瀆濸 瀇瀊瀂 濹濴濶瀇瀂瀅瀆, 
瀇濻濸 RNTM 瀊濼濿濿 濷濸濿濼瀉濸瀅 瀇濻濸 瀂瀃濴瀄瀈濸 濸瀁瀉濸濿瀂瀃濸瀆 濶瀂瀁瀇濴濼瀁濼瀁濺 瀇濻濸 
瀅濴瀁濷瀂瀀 濴濿濿瀂濶濴瀇濼瀂瀁 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 瀇瀂 瀇濻濸 濵濸濷瀆濼濷濸 瀁瀈瀅瀆濸 濵濸濹瀂瀅濸 
8:00 濴.瀀. 瀂瀁 瀇濻濸 濹濼瀅瀆瀇 濷濴瀌 濴濹瀇濸瀅 瀆瀈瀅濺濸瀅瀌. T濻濸 濵濸濷瀆濼濷濸 瀁瀈瀅瀆濸 瀊濼濿濿 
瀇濻濸瀁 瀂瀃濸瀁 瀇濻濸 濸瀁瀉濸濿瀂瀃濸 濴瀁濷 瀃濸瀅濹瀂瀅瀀 濶瀂瀅瀅濸瀆瀃瀂瀁濷濼瀁濺 
瀃瀅瀂濶濸濷瀈瀅濸瀆 瀂瀁 瀇濻濸 瀃濴瀇濼濸瀁瀇 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 濺瀅瀂瀈瀃濼瀁濺 
濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 濼瀁瀆濼濷濸. T濻濸 RNTM 濼瀆 濼瀁濷濸瀃濸瀁濷濸瀁瀇 瀂濹 瀂瀇濻濸瀅 
瀃濸瀅瀆瀂瀁瀁濸濿 濼瀁瀉瀂濿瀉濸濷 濼瀁 瀇濻濼瀆 瀆瀇瀈濷瀌, 濷瀂 瀁瀂瀇 瀃濴瀅瀇濼濶濼瀃濴瀇濸 濼瀁 濴瀁瀌 瀂瀇濻濸瀅 
濶濿濼瀁濼濶濴濿 瀂瀃濸瀅濴瀇濼瀂瀁瀆 瀂濹 瀇濻濼瀆 瀆瀇瀈濷瀌, 濴瀁濷 濻濴瀉濸 瀁瀂 濾瀁瀂瀊濿濸濷濺濸 瀂濹 濴瀁瀌 
瀂瀇濻濸瀅 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 濴濵瀂瀈瀇 瀇濻濸 瀃濴瀇濼濸瀁瀇瀆.
T濻濸 瀁濸瀊 瀃瀅瀂瀇瀂濶瀂濿 濷濸瀆濶瀅濼濵濸瀆 瀇濻濸 瀅濴瀁濷瀂瀀 濴濿濿瀂濶濴瀇濼瀂瀁 瀀濸瀇濻瀂濷 濴瀁濷 
濶瀂瀁濶濸濴濿瀀濸瀁瀇 瀀濸瀇濻瀂濷 濼瀁 瀀瀂瀅濸 濷濸瀇濴濼濿, 濴濿濿瀂瀊濼瀁濺 瀂瀇濻濸瀅 瀅濸瀆濸濴瀅濶濻濸瀅瀆 
瀇瀂 濻濴瀉濸 濴 瀀瀂瀅濸 濷濸瀇濴濼濿濸濷 濴瀁濷 濶濿濸濴瀅 瀈瀁濷濸瀅瀆瀇濴瀁濷濼瀁濺 瀂濹 瀇濻濼瀆 瀃濴瀅瀇 瀂濹 
瀇濻濸 瀊瀂瀅濾.
6.3 P濴瀇濼濸瀁瀇 濶瀂瀀瀃濿濼濴瀁濶濸 濴瀁濷 
瀊濼瀇濻濷瀅濴瀊濴濿
……I濹 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀆瀇濼濿濿 濼瀁瀆濼瀆瀇瀆 瀂瀁 瀊濼瀇濻濷瀅濴瀊濼瀁濺, 瀇濻濸濼瀅 瀃瀅濸濹濸瀅濸瀁濶濸 
瀊濼濿濿 濵濸 瀅濸瀆瀃濸濶瀇濸濷, 濴瀁濷 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀊濼濿濿 濵濸 濸瀋濶濿瀈濷濸濷 濹瀅瀂瀀 瀇濻濸 
瀇瀅濼濴濿. T濻濸 濶濿濼瀁濼濶濴濿 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 瀅濸濿濴瀇濸濷 瀇瀂 瀇濻濼瀆 瀃濴瀇濼濸瀁瀇 瀊濼濿濿 瀁瀂瀇 濵濸 
濼瀁濶濿瀈濷濸濷 濼瀁 濴瀁瀌 濷濴瀇濴 濴瀁濴濿瀌瀆濼瀆 瀅濸濿濴瀇濸濷 瀇瀂 瀇濻濼瀆 瀇瀅濼濴濿.
……I濹 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀆瀇濼濿濿 濼瀁瀆濼瀆瀇瀆 瀂瀁 瀊濼瀇濻濷瀅濴瀊濼瀁濺 濹瀅瀂瀀 瀇濻濸 瀆瀇瀈濷瀌 濴瀁濷 
瀅濸濹瀈瀆濸瀆 瀇瀂 濴濿濿瀂瀊 瀇濻濸 瀈瀆濸 瀂濹 瀃濸瀅瀆瀂瀁濴濿 濷濴瀇濴 濼瀁 瀇濻濼瀆 瀅濸瀆濸濴瀅濶濻 
瀃瀅瀂濽濸濶瀇, 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀆濻濴濿濿 濵濸 瀊濼瀇濻濷瀅濴瀊瀁 濹瀅瀂瀀 瀇濻濸 瀆瀇瀈濷瀌 
濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 瀃濴瀇濼濸瀁瀇'瀆 瀊濼瀆濻, 濴瀁濷 濴濿濿 濷濴瀇濴 瀂濹 瀇濻濼瀆 瀃濴瀇濼濸瀁瀇 瀆濻濴濿濿 
濵濸 瀇瀅濸濴瀇濸濷 濴瀆 瀀濼瀆瀆濼瀁濺 濷濴瀇濴. D瀈瀅濼瀁濺 瀇濻濸 濹瀂濿濿瀂瀊-瀈瀃 瀃濻濴瀆濸 瀂濹 瀇濻濸 
瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇, 濼濹 濴 瀃濴瀇濼濸瀁瀇 瀅濸濹瀈瀆濸瀆 瀇瀂 濶瀂瀂瀃濸瀅濴瀇濸 瀊濼瀇濻 瀇濻濸 
濹瀂濿濿瀂瀊-瀈瀃 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇, 濼瀁濶濿瀈濷濼瀁濺 瀇濻濸 濹瀂濿濿瀂瀊-瀈瀃 瀂濹 
瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濴瀁濷 瀇濻濸 濴瀆瀆濸瀆瀆瀀濸瀁瀇 瀂濹 瀅濸瀆濼濷瀈濴濿 瀈瀅濼瀁濸 
瀉瀂濿瀈瀀濸, 瀇濻濸 瀃瀅濼瀁濶濼瀃濴濿 濼瀁瀉濸瀆瀇濼濺濴瀇瀂瀅 瀆濻濴濿濿 濶瀂瀀瀀瀈瀁濼濶濴瀇濸 瀊濼瀇濻 瀇濻濸 
瀃濴瀇濼濸瀁瀇 濴瀁濷 濴瀃瀃瀅瀂瀃瀅濼濴瀇濸濿瀌 濼瀁濶瀅濸濴瀆濸 瀇濻濸 濶瀂瀀瀃濸瀁瀆濴瀇濼瀂瀁 濹瀂瀅 瀇濻濸 
瀆瀈濵濽濸濶瀇瀆 瀇瀂 濴瀉瀂濼濷 瀇濻濸 濴濵瀆濸瀁濶濸 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇. I濹 瀇濻濸 
瀃濴瀇濼濸瀁瀇 瀆瀇瀈濵濵瀂瀅瀁濿瀌 瀅濸濹瀈瀆濸瀆 瀇瀂 濶瀂瀂瀃濸瀅濴瀇濸 瀊濼瀇濻 瀇濻濸 濹瀂濿濿瀂瀊-瀈瀃 瀂濹 
瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇, 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇 瀂濹 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀆濻濴濿濿 
濵濸 瀇瀅濸濴瀇濸濷 濴瀆 瀀濼瀆瀆濼瀁濺 濷濴瀇濴, 濴瀁濷 瀂瀇濻濸瀅 濷濴瀇濴 瀆濻濴濿濿 濵濸 瀅濸濶瀂瀅濷濸濷 濼瀁 
瀇濻濸 濷濴瀇濴濵濴瀆濸.  
T濻濸 濻濴瀁濷濿濼瀁濺 瀀濸瀇濻瀂濷瀆 瀊濻濸瀁 瀃濴瀇濼濸瀁瀇瀆 瀅濸瀄瀈濸瀆瀇 瀇瀂 瀊濼瀇濻濷瀅濴瀊 濹瀅瀂瀀 
瀇濻濸 瀆瀇瀈濷瀌 濻濴瀉濸 濵濸濸瀁 瀆瀈瀃瀃濿濸瀀濸瀁瀇濸濷 濼瀁 瀀瀂瀅濸 濷濸瀇濴濼濿, 濴瀆 瀊濸濿濿 濴瀆 
瀇濻濸 濴瀃瀃瀅瀂濴濶濻濸瀆 瀇瀂 瀅濸濷瀈濶濸 瀇濻濸 濿瀂瀆瀆 瀇瀂 濹瀂濿濿瀂瀊-瀈瀃, 濴瀁濷 瀇濻濸 
瀃瀅濼瀁濶濼瀃濿濸瀆 濹瀂瀅 瀃瀅瀂濶濸瀆瀆濼瀁濺 瀇濻濸 瀅濸濿濸瀉濴瀁瀇 濷濴瀇濴 瀂濹 瀇濻濸瀆濸 瀃濴瀇濼濸瀁瀇瀆. 
9. D濴瀇濴 瀃瀅瀂濶濸瀆瀆濼瀁濺 濴瀁濷 瀆瀇瀂瀅濴濺濸
A濿濿 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 瀀濸濸瀇 瀇濻濸 濼瀁濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴 瀊濼濿濿 濵濸 瀅濸濺濼瀆瀇濸瀅濸濷, 
濼瀁濶濿瀈濷濼瀁濺 瀇濻瀂瀆濸 瀊濻瀂 瀅濸濹瀈瀆濸 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁, 瀇濻瀂瀆濸 濸瀋濶濿瀈濷濸濷 濷瀈濸 
瀇瀂 濸瀋濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴, 濴瀁濷 瀇濻瀂瀆濸 瀊濻瀂 濴瀅濸 瀊濼瀇濻濷瀅濴瀊瀁 濴濹瀇濸瀅 
瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 濷瀈濸 瀇瀂 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴. R濸濴瀆瀂瀁瀆 濹瀂瀅 濸瀋濶濿瀈瀆濼瀂瀁 
濴瀁濷 瀊濼瀇濻濷瀅濴瀊濴濿 瀊濼濿濿 濵濸 瀅濸濶瀂瀅濷濸濷.
D濸濿濸瀇濸 瀇濻濼瀆 瀃濴瀅濴濺瀅濴瀃濻
T濻濼瀆 瀃濴瀅瀇 濷瀂濸瀆 瀁瀂瀇 濹濴濿濿 瀊濼瀇濻濼瀁 瀇濻濸 瀆濶瀂瀃濸 瀂濹 瀇濻濸 濶瀂瀁瀇濸瀁瀇 瀂濹 "D濴瀇濴 
P瀅瀂濶濸瀆瀆濼瀁濺 濴瀁濷 S瀇瀂瀅濴濺濸." T濻濸 濶瀂瀅瀅濸瀆瀃瀂瀁濷濼瀁濺 濷濸瀆濶瀅濼瀃瀇濼瀂瀁 濻濴瀆 
濵濸濸瀁 瀅濸瀉濼瀆濸濷 濴瀁濷 濴濷濷濸濷 瀇瀂 "12.1 C濴瀆濸 R濸瀃瀂瀅瀇 F瀂瀅瀀/E濿濸濶瀇瀅瀂瀁濼濶 
D濴瀇濴 R濸濶瀂瀅濷." 
10. Q瀈濴濿濼瀇瀌 瀀濴瀁濴濺濸瀀濸瀁瀇 （2）
I瀁瀇濸瀅瀉濸瀁瀇濼瀂瀁濴濿 瀀濸瀇濻瀂濷 瀄瀈濴濿濼瀇瀌 濶瀂瀁瀇瀅瀂濿
7) D瀈瀅濼瀁濺 瀇濻濸 濹濼瀅瀆瀇 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁, 瀆濸濿濸濶瀇濼瀉濸 α1-濴濷瀅濸瀁濸瀅濺濼濶 
瀅濸濶濸瀃瀇瀂瀅 濵濿瀂濶濾濸瀅瀆 (瀆瀈濶濻 濴瀆 瀇濴瀀瀆瀈濿瀂瀆濼瀁) 瀆濻瀂瀈濿濷 瀁瀂瀇 濵濸 瀈瀆濸濷. I濹 
瀀濸濷濼濶濴濿濿瀌 瀁濸濶濸瀆瀆濴瀅瀌, 瀇濻濸 瀃濴瀇濼濸瀁瀇 瀀瀈瀆瀇 瀊濼瀇濻濷瀅濴瀊 濹瀅瀂瀀 瀇濻濸 瀇瀅濼濴濿. 
7) D瀈瀅濼瀁濺 瀇濻濸 濹濼瀅瀆瀇 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 瀂濹 瀇濻濸 瀃濴瀇濼濸瀁瀇, 瀆濸濿濸濶瀇濼瀉濸 α1-
濴濷瀅濸瀁濸瀅濺濼濶 瀅濸濶濸瀃瀇瀂瀅 濵濿瀂濶濾濸瀅瀆 (瀆瀈濶濻 濴瀆 T濴瀀瀆瀈濿瀂瀆濼瀁) 瀆濻瀂瀈濿濷 瀁瀂瀇 
濵濸 瀈瀆濸濷. I濹 濼瀇 濼瀆 瀁濸濶濸瀆瀆濴瀅瀌 瀇瀂 瀈瀆濸 瀇濻濸瀀 濷瀈濸 瀇瀂 瀇濻濸 瀃濴瀇濼濸瀁瀇'瀆 
濶瀂瀁濷濼瀇濼瀂瀁, 瀇濻濸 瀅濸濴瀆瀂瀁瀆 瀆濻瀂瀈濿濷 濵濸 瀅濸濶瀂瀅濷濸濷; 8) E濴濶濻 瀃濴瀇濼濸瀁瀇 
濸瀁瀅瀂濿濿濸濷 濼瀁 瀇濻濸 瀆瀇瀈濷瀌 瀊濼濿濿 濵濸 濺濼瀉濸瀁 濴 瀆瀈濵濽濸濶瀇 濶瀂瀀瀃濸瀁瀆濴瀇濼瀂瀁 瀂濹 
100 瀌瀈濴瀁 瀇瀂 濼瀁濶瀅濸濴瀆濸 瀇濻濸 濶瀂瀀瀃濿濼濴瀁濶濸 瀂濹 瀇濻濸 濸瀁瀅瀂濿濿濸濷 瀃濴瀇濼濸瀁瀇瀆 
濴瀁濷 瀇濻濸 瀆瀈濶濶濸瀆瀆 瀅濴瀇濸 瀂濹 濹瀂濿濿瀂瀊-瀈瀃. 
P濴瀇濼濸瀁瀇瀆 瀊濻瀂 瀈瀆濸 α1-濴濷瀅濸瀁濸瀅濺濼濶 瀅濸濶濸瀃瀇瀂瀅 濵濿瀂濶濾濸瀅瀆 濼瀁 瀇濻濸 瀁濸瀊 
瀃瀅瀂瀇瀂濶瀂濿 瀊濼濿濿 瀆瀇濼濿濿 濵濸 濼瀁濶濿瀈濷濸濷 濼瀁 瀇濻濸 I瀁瀇濸瀁瀇濼瀂瀁-瀇瀂-T瀅濸濴瀇 (ITT) 
濴瀁濴濿瀌瀆濼瀆 瀇瀂 濴瀉瀂濼濷 瀇濻濸 濼瀀瀃濴濶瀇 瀂濹 瀃濴瀇濼濸瀁瀇 瀊濼瀇濻濷瀅濴瀊濴濿 瀂瀁 瀇濻濸 
濵濴濿濴瀁濶濸 瀂濹 濶瀂瀀瀃瀂瀁濸瀁瀇瀆 濴濹瀇濸瀅 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁. P濴瀇濼濸瀁瀇瀆 瀊濻瀂 濷瀂 
瀁瀂瀇 瀀濸濸瀇 瀇濻濸 瀃瀅瀂瀇瀂濶瀂濿 瀊濼濿濿 濵濸 濸瀋濶濿瀈濷濸濷 濹瀅瀂瀀 瀇濻濸 P濸瀅-P瀅瀂瀇瀂濶瀂濿 
A瀁濴濿瀌瀆濼瀆 (PPA) 瀆濸瀇. I瀁 濴濷濷濼瀇濼瀂瀁, 濴 瀀濸濴瀆瀈瀅濸 濻濴瀆 濵濸濸瀁 濴濷濷濸濷 瀇瀂 
瀅濸濷瀈濶濸 瀇濻濸 瀅濴瀇濸 瀂濹 濿瀂瀆瀆 瀇瀂 濹瀂濿濿瀂瀊-瀈瀃. 
10. Q瀈濴濿濼瀇瀌 瀀濴瀁濴濺濸瀀濸瀁瀇 （3）
E瀁濷瀃瀂濼瀁瀇 瀄瀈濴濿濼瀇瀌 濶瀂瀁瀇瀅瀂濿
3) F瀂瀅 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 濹濴濼濿 瀇瀂 瀈瀁濷濸瀅濺瀂 瀇濻濸 瀅濸瀆濼濷瀈濴濿 瀈瀅濼瀁濸 瀉瀂濿瀈瀀濸 
濴瀆瀆濸瀆瀆瀀濸瀁瀇 濼瀁 濴 瀇濼瀀濸濿瀌 瀀濴瀁瀁濸瀅 濹瀂瀅 瀉濴瀅濼瀂瀈瀆 瀅濸濴瀆瀂瀁瀆 濴濹瀇濸瀅 瀇濻濸 
濹濼瀅瀆瀇 瀈瀅濼瀁濴瀇濼瀂瀁, 濴 濵濿濴濷濷濸瀅 瀈濿瀇瀅濴瀆瀂瀈瀁濷 瀆濻瀂瀈濿濷 濵濸 濶瀂瀁濷瀈濶瀇濸濷 
濼瀀瀀濸濷濼濴瀇濸濿瀌 濴濹瀇濸瀅 瀇濻濸 瀆濸濶瀂瀁濷 瀈瀅濼瀁濴瀇濼瀂瀁, 濴瀁濷 瀇濻濼瀆 瀆濼瀇瀈濴瀇濼瀂瀁 
瀆濻瀂瀈濿濷 濵濸 瀅濸濶瀂瀅濷濸濷; 4) F瀂瀅 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂瀆濸 濹濼瀅瀆瀇 瀈瀅濼瀁濴瀇濼瀂瀁 瀂濶濶瀈瀅瀆 
濴濹瀇濸瀅 18:00 濹瀂濿濿瀂瀊濼瀁濺 瀇濻濸 瀅濸瀀瀂瀉濴濿 瀂濹 瀇濻濸 瀈瀅濼瀁濴瀅瀌 濶濴瀇濻濸瀇濸瀅, 瀆濼瀁濶濸 
瀇濻濸 濷濸瀆濼濺瀁濴瀇濸濷 瀈濿瀇瀅濴瀆瀂瀈瀁濷 瀃濻瀌瀆濼濶濼濴瀁 濹瀂瀅 濴瀆瀆濸瀆瀆瀀濸瀁瀇 濻濴瀆 
濴濿瀅濸濴濷瀌 濿濸濹瀇 瀊瀂瀅濾 濴瀁濷 濼瀆 瀈瀁濴濵濿濸 瀇瀂 濶瀂瀁濷瀈濶瀇 瀂瀁-瀆濼瀇濸 濴瀆瀆濸瀆瀆瀀濸瀁瀇, 
瀇濻濸 瀅濸瀆濼濷瀈濴濿 瀈瀅濼瀁濸 瀉瀂濿瀈瀀濸 濴瀆瀆濸瀆瀆瀀濸瀁瀇 瀊濼濿濿 濵濸 濶濴瀅瀅濼濸濷 瀂瀈瀇 濵瀌 瀇濻濸 
瀈濿瀇瀅濴瀆瀂瀈瀁濷 瀃濻瀌瀆濼濶濼濴瀁 瀂瀁 24-濻瀂瀈瀅 濷瀈瀇瀌 濼瀁 瀇濻濸 濻瀂瀆瀃濼瀇濴濿, 濴瀁濷 瀇濻濼瀆 
瀆濼瀇瀈濴瀇濼瀂瀁 瀆濻瀂瀈濿濷 濵濸 瀅濸濶瀂瀅濷濸濷.
M濸濴瀆瀈瀅濸瀆 濻濴瀉濸 濵濸濸瀁 濴濷濷濸濷 瀇瀂 濴瀉瀂濼濷 瀇濻濸 瀀濼瀆瀆濼瀁濺 瀂濹 瀃瀅濼瀀濴瀅瀌 
濸瀁濷瀃瀂濼瀁瀇瀆, 濴瀆 瀊濸濿濿 濴瀆 瀅濸瀀濸濷濼濸瀆 濴濹瀇濸瀅 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇瀆 濴瀅濸 
瀀濼瀆瀆濼瀁濺, 瀇瀂 濹濴濶濼濿濼瀇濴瀇濸 瀇濻濸 瀆瀈濵瀆濸瀄瀈濸瀁瀇 瀃瀅瀂濶濸瀆瀆濼瀁濺 瀂濹 瀀濼瀆瀆濼瀁濺 
濷濴瀇濴.

11.2.1 F瀈濿濿 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇
T濻濸 濶瀂瀀瀃濴瀅濴瀇濼瀉濸 濴瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 瀂瀈瀇濶瀂瀀濸瀆 瀊濼濿濿 濵濸 
濶瀂瀁濷瀈濶瀇濸濷 瀂瀁 瀇濻濸 濵濴瀆濼瀆 瀂濹 瀇濻濸 "瀀瀂濷濼濹濼濸濷 濼瀁瀇濸瀁瀇濼瀂瀁-瀇瀂-瀇瀅濸濴瀇 
(瀀ITT)". T濻濸 瀀ITT 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 濼瀁濶濿瀈濷濸 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 濷濼濷 瀁瀂瀇 
濹瀂濿濿瀂瀊 瀇濻濸 瀅濴瀁濷瀂瀀濿瀌 濴瀆瀆濼濺瀁濸濷 瀀濸濴瀆瀈瀅濸瀆 濵瀈瀇 瀊濸瀅濸 瀁瀂瀇 濸瀋濶濿瀈濷濸濷 
濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴. I瀁 瀇濻濼瀆 瀆瀇瀈濷瀌, 濼濹 濴 瀃濴瀇濼濸瀁瀇 
瀀濸濸瀇瀆 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴 濴濹瀇濸瀅 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁, 瀇濻濼瀆 瀃濴瀇濼濸瀁瀇 
瀊濼濿濿 濵濸 濸瀋濶濿瀈濷濸濷, 濴瀁濷 瀇濻濸 瀅濸濿濸瀉濴瀁瀇 濷濴瀇濴 瀂濹 瀇濻濼瀆 瀃濴瀇濼濸瀁瀇 瀊濼濿濿 瀁瀂瀇 
濴瀃瀃濸濴瀅 濼瀁 瀇濻濸 瀆瀇濴瀇濼瀆瀇濼濶濴濿 濴瀁濴濿瀌瀆濼瀆 濼瀁濶濿瀈濷濼瀁濺 瀇濻濸 瀀ITT 濴瀁濴濿瀌瀆濼瀆. I瀁 
瀇濻濸 瀀ITT 濴瀁濴濿瀌瀆濼瀆, 濹瀂瀅 瀃濴瀇濼濸瀁瀇瀆 瀅濴瀁濷瀂瀀濿瀌 濴瀆瀆濼濺瀁濸濷 瀇瀂 瀇濻濸 
濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濺瀅瀂瀈瀃, 濼濹 瀇濻濸 濶濴瀇濻濸瀇濸瀅 濼瀆 濷濼瀅濸濶瀇濿瀌 瀅濸瀀瀂瀉濸濷 
瀊濼瀇濻瀂瀈瀇 瀈瀁濷濸瀅濺瀂濼瀁濺 瀇瀅濴濼瀁濼瀁濺 濴瀇 瀇濻濸 濸瀁濷, 瀇濻濸 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 瀆瀇濼濿濿 濵濸 
濶濴瀅瀅濼濸濷 瀂瀈瀇 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濺瀅瀂瀈瀃; 濹瀂瀅 
瀃濴瀇濼濸瀁瀇瀆 瀅濴瀁濷瀂瀀濿瀌 濴瀆瀆濼濺瀁濸濷 瀇瀂 瀇濻濸 濷濼瀅濸濶瀇 瀅濸瀀瀂瀉濴濿 濺瀅瀂瀈瀃, 濼濹 瀇濻濸瀌 
瀅濸濶濸濼瀉濸 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濴瀇 瀇濻濸 濸瀁濷, 瀇濻濸 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 瀆瀇濼濿濿 濵濸 
濶濴瀅瀅濼濸濷 瀂瀈瀇 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 濷濼瀅濸濶瀇 瀅濸瀀瀂瀉濴濿 濺瀅瀂瀈瀃. I瀁 濴濷濷濼瀇濼瀂瀁, 
濼濹 濴 瀃濴瀇濼濸瀁瀇 瀈瀁濷濸瀅濺瀂濸瀆 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁, 濷瀂濸瀆 瀁瀂瀇 
瀀濸濸瀇 瀇濻濸 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴, 濵瀈瀇 瀇濻濸 瀈瀅濼瀁濸 瀉瀂濿瀈瀀濸 濷瀅濴瀊瀁 濴濹瀇濸瀅 
瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濼瀆 濿濸瀆瀆 瀇濻濴瀁 100瀀濿. W濸 瀊濼濿濿 瀁瀂瀇 
濶瀂瀁瀆濼濷濸瀅 瀇濻濴瀇 瀇濻濼瀆 瀆濸濶瀂瀁濷濴瀅瀌 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濼瀆 濶濴瀈瀆濸濷 濵瀌 
濵濿濴濷濷濸瀅 濸瀀瀃瀇瀌濼瀁濺 濷濼瀆瀂瀅濷濸瀅. I瀁 瀇濻濸 濴瀁濴濿瀌瀆濼瀆, 瀊濸 瀊濼濿濿 瀁瀂瀇 濶濿濴瀆瀆濼濹瀌 
瀆瀈濶濻 瀃濴瀇濼濸瀁瀇瀆 濴瀆 濻濴瀉濼瀁濺 瀈瀅濼瀁濴瀅瀌 濷瀌瀆濹瀈瀁濶瀇濼瀂瀁. I瀁 瀇濻濸 瀀ITT 
濴瀁濴濿瀌瀆濼瀆, 瀊濸 瀊濼濿濿 瀆瀇濼濿濿 濼瀁濶濿瀈濷濸 瀇濻濸瀆濸 瀃濴瀇濼濸瀁瀇瀆 濼瀁 瀇濻濸 濴瀁濴濿瀌瀆濼瀆, 濵瀈瀇 
濼瀁瀆瀇濸濴濷 瀂濹 濶濿濴瀆瀆濼濹瀌濼瀁濺 瀇濻濸瀀 濴瀆 濸瀁濷-瀃瀂濼瀁瀇 濸瀉濸瀁瀇瀆 (瀃瀂瀆濼瀇濼瀉濸 
濸瀉濸瀁瀇瀆), 瀊濸 瀊濼濿濿 濴瀁濴濿瀌瀍濸 瀇濻濸瀀 濴瀆 瀁濸濺濴瀇濼瀉濸 濸瀉濸瀁瀇瀆.
T濻濸 濶瀂瀀瀃濴瀅濴瀇濼瀉濸 濴瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 瀂瀈瀇濶瀂瀀濸 瀊濼濿濿 濵濸 
濶瀂瀁濷瀈濶瀇濸濷 瀂瀁 瀇濻濸 濵濴瀆濼瀆 瀂濹 瀇濻濸 "I瀁瀇濸瀁瀇濼瀂瀁-瀇瀂-T瀅濸濴瀇 (ITT)" 
瀃瀅濼瀁濶濼瀃濿濸. T濻濸 ITT 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 濼瀁濶濿瀈濷濸 濴濿濿 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 濻濴瀉濸 
瀈瀁濷濸瀅濺瀂瀁濸 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁. I瀁 瀇濻濸 ITT 濴瀁濴濿瀌瀆濼瀆, 濹瀂瀅 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 
濴瀅濸 瀅濴瀁濷瀂瀀濼瀍濸濷 瀇瀂 瀇濻濸 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濺瀅瀂瀈瀃 濵瀈瀇 濻濴瀉濸 瀇濻濸 
瀈瀅濼瀁濴瀅瀌 濶濴瀇濻濸瀇濸瀅 瀅濸瀀瀂瀉濸濷 濷濼瀅濸濶瀇濿瀌 瀊濼瀇濻瀂瀈瀇 瀈瀁濷濸瀅濺瀂濼瀁濺 瀇濻濸 
瀇瀅濴濼瀁濼瀁濺 瀈濿瀇濼瀀濴瀇濸濿瀌, 瀇濻濸瀌 瀊濼濿濿 瀆瀇濼濿濿 濵濸 濴瀁濴濿瀌瀍濸濷 濴瀆 瀃濴瀅瀇 瀂濹 瀇濻濸 
濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濺瀅瀂瀈瀃. F瀂瀅 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 濴瀅濸 瀅濴瀁濷瀂瀀濼瀍濸濷 瀇瀂 
瀇濻濸 濷濼瀅濸濶瀇 濶濴瀇濻濸瀇濸瀅 瀅濸瀀瀂瀉濴濿 濺瀅瀂瀈瀃 濵瀈瀇 濻濴瀉濸 瀅濸濶濸濼瀉濸濷 濵濿濴濷濷濸瀅 
瀇瀅濴濼瀁濼瀁濺 濼瀁 瀇濻濸 濸瀁濷, 瀇濻濸瀌 瀊濼濿濿 瀆瀇濼濿濿 濵濸 濴瀁濴濿瀌瀍濸濷 濴瀆 瀃濴瀅瀇 瀂濹 瀇濻濸 
濷濼瀅濸濶瀇 濶濴瀇濻濸瀇濸瀅 瀅濸瀀瀂瀉濴濿 濺瀅瀂瀈瀃. 
T濻濸 瀃瀅濼瀀濴瀅瀌 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇 濼瀁 瀇濻濸 瀁濸瀊 瀉濸瀅瀆濼瀂瀁 瀂濹 瀇濻濸 瀃瀅瀂瀇瀂濶瀂濿 濻濴瀆 
濵濸濸瀁 濶濻濴瀁濺濸濷 瀇瀂 瀇濻濸 I瀁瀇濸瀁瀇濼瀂瀁-瀇瀂-T瀅濸濴瀇 (ITT) 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇. T濻濴瀇 
濼瀆, 濴濿濿 瀃濴瀇濼濸瀁瀇瀆 濼瀁濶濿瀈濷濸濷 濼瀁 瀇濻濸 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 瀊濼濿濿 濵濸 濼瀁濶濿瀈濷濸濷 濼瀁 
瀇濻濸 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇, 瀆瀂 濴瀆 瀇瀂 瀃瀅濸瀉濸瀁瀇 瀈瀁瀁濸濶濸瀆瀆濴瀅瀌 瀃濴瀇濼濸瀁瀇 
瀊濼瀇濻濷瀅濴瀊濴濿瀆 濹瀅瀂瀀 濷濼瀆瀅瀈瀃瀇濼瀁濺 瀇濻濸 濼瀁瀇濸瀅-濺瀅瀂瀈瀃 濵濴濿濴瀁濶濸 濴濹瀇濸瀅 
瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 瀂濹 瀇濻濸 瀇瀅濼濴濿 濴瀁濷 濼瀁瀇瀅瀂濷瀈濶濼瀁濺 瀆濸濿濸濶瀇濼瀂瀁 濵濼濴瀆.
11.2.2 P濸瀅-瀃瀅瀂瀇瀂濶瀂濿 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇
E瀋濶濿瀈濷濸濷 瀃濴瀇濼濸瀁瀇瀆 濼瀁濶濿瀈濷濸 瀇濻瀂瀆濸 瀊濻瀂 濷濼濷 瀁瀂瀇 濻濴瀉濸 瀇濻濸 濶濴瀇濻濸瀇濸瀅 
瀅濸瀀瀂瀉濸濷 瀂瀁 瀇濻濸 瀆濸濶瀂瀁濷 瀃瀂瀆瀇瀂瀃濸瀅濴瀇濼瀉濸 濷濴瀌, 濴瀆 瀊濸濿濿 濴瀆 瀇濻瀂瀆濸 
瀊濻瀂瀆濸 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 瀊濴瀆 瀁瀂瀇 濶瀂瀁濷瀈濶瀇濸濷 瀆瀇瀅濼濶瀇濿瀌 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 
瀃濿濴瀁.
T濻濸 瀃濴瀇濼濸瀁瀇瀆 瀇瀂 濵濸 濸瀋濶濿瀈濷濸濷 濼瀁濶濿瀈濷濸: 1) P濴瀇濼濸瀁瀇瀆 瀊濻瀂瀆濸 瀈瀅濼瀁濴瀅瀌 
濶濴瀇濻濸瀇濸瀅瀆 瀊濸瀅濸 瀁瀂瀇 瀅濸瀀瀂瀉濸濷 瀂瀁 瀇濻濸 瀆濸濶瀂瀁濷 濷濴瀌 濴濹瀇濸瀅 瀇濻濸 
瀂瀃濸瀅濴瀇濼瀂瀁 濹瀂瀅 瀉濴瀅濼瀂瀈瀆 瀅濸濴瀆瀂瀁瀆, 濸濼瀇濻濸瀅 瀊濼瀇濻 瀇濻濸 瀅濸瀀瀂瀉濴濿 瀇濼瀀濸 
濴濷瀉濴瀁濶濸濷 瀂瀅 瀃瀂瀆瀇瀃瀂瀁濸濷; 2) P濴瀇濼濸瀁瀇瀆 瀊濻瀂 濷濼濷 瀁瀂瀇 濶濴瀅瀅瀌 瀂瀈瀇 瀇濻濸 
濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 瀆瀇瀅濼濶瀇濿瀌 濴濶濶瀂瀅濷濼瀁濺 瀇瀂 瀇濻濸 瀃濿濴瀁; 3) P濴瀇濼濸瀁瀇瀆 瀊濻瀂 
濻濴濷 瀇瀂 瀈瀆濸 瀆濸濿濸濶瀇濼瀉濸 α1-濴濷瀅濸瀁濸瀅濺濼濶 瀅濸濶濸瀃瀇瀂瀅 濵濿瀂濶濾濸瀅瀆 濷瀈濸 瀇瀂 
瀇濻濸濼瀅 瀀濸濷濼濶濴濿 濶瀂瀁濷濼瀇濼瀂瀁瀆 濷瀈瀅濼瀁濺 瀇濻濸 濹濼瀅瀆瀇 濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁.
E濿濴濵瀂瀅濴瀇濸 濼瀁 瀀瀂瀅濸 濷濸瀇濴濼濿 瀂瀁 瀇濻濸 瀃瀂瀃瀈濿濴瀇濼瀂瀁 瀇濻濴瀇 濶瀂瀁濹瀂瀅瀀瀆 瀇瀂 
瀇濻濸 瀃濸瀅-瀃瀅瀂瀇瀂濶瀂濿 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇. 
11.2.3 A瀆-瀇瀅濸濴瀇濸濷 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇
I瀁 瀇濻濸 ATA 濴瀁濴濿瀌瀆濼瀆, 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 瀅濸濶濸濼瀉濸 濴瀇 濿濸濴瀆瀇 瀂瀁濸 瀅瀂瀈瀁濷 瀂濹 
濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濴瀅濸 濶濿濴瀆瀆濼濹濼濸濷 濴瀆 瀇濻濸 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濺瀅瀂瀈瀃, 
瀊濻濼濿濸 瀇濻瀂瀆濸 瀊濻瀂 濷瀂 瀁瀂瀇 瀅濸濶濸濼瀉濸 瀇瀅濴濼瀁濼瀁濺 濴瀅濸 濶濿濴瀆瀆濼濹濼濸濷 濴瀆 瀇濻濸 
濷濼瀅濸濶瀇 瀅濸瀀瀂瀉濴濿 濺瀅瀂瀈瀃.
T濻濸 ATA 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇 瀊濼濿濿 濼瀁濶濿瀈濷濸 濴濿濿 瀇濻濸 瀃濴瀇濼濸瀁瀇瀆 濼瀁 瀇濻濸 ITT 
濴瀁濴濿瀌瀆濼瀆 瀆濸瀇. H瀂瀊濸瀉濸瀅, 濼瀁 瀇濸瀅瀀瀆 瀂濹 濺瀅瀂瀈瀃濼瀁濺, 濼瀁 瀇濻濸 ATA 濴瀁濴濿瀌瀆濼瀆, 
瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 瀅濸濶濸濼瀉濸 濴瀇 濿濸濴瀆瀇 瀂瀁濸 瀅瀂瀈瀁濷 瀂濹 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濴瀅濸 
濶濿濴瀆瀆濼濹濼濸濷 濴瀆 瀇濻濸 濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺 濺瀅瀂瀈瀃, 瀊濻濼濿濸 瀇濻瀂瀆濸 瀊濻瀂 濷瀂 
瀁瀂瀇 瀅濸濶濸濼瀉濸 瀇瀅濴濼瀁濼瀁濺 濴瀅濸 濶濿濴瀆瀆濼濹濼濸濷 濴瀆 瀇濻濸 濷濼瀅濸濶瀇 瀅濸瀀瀂瀉濴濿 濺瀅瀂瀈瀃. 
E濿濴濵瀂瀅濴瀇濸 濼瀁 瀀瀂瀅濸 濷濸瀇濴濼濿 瀂瀁 瀇濻濸 瀃瀂瀃瀈濿濴瀇濼瀂瀁 瀂濹 瀇濻濸 濴瀆-瀇瀅濸濴瀇濸濷 
濴瀁濴濿瀌瀆濼瀆 瀆濸瀇.
11.3 M濼瀆瀆濼瀁濺 濷濴瀇濴 濴瀁濷 濼瀇瀆 濻濴瀁濷濿濼瀁濺 
濴瀃瀃瀅瀂濴濶濻濸瀆
S濸濶瀇濼瀂瀁 “11.3 M濼瀆瀆濼瀁濺 濷濴瀇濴 濴瀁濷 濼瀇瀆 濻濴瀁濷濿濼瀁濺 濴瀃瀃瀅瀂濴濶濻濸瀆” 濻濴瀆 
濵濸濸瀁 瀆瀈瀃瀃濿濸瀀濸瀁瀇濸濷. 
T濻濸 瀀濼瀆瀆濼瀁濺 濷濴瀇濴 濼瀁 瀇濻濸 瀆瀇瀈濷瀌 濴瀁濷 瀇濻濸濼瀅 濻濴瀁濷濿濼瀁濺 瀀濸瀇濻瀂濷瀆 濻濴瀉濸 
濵濸濸瀁 濷濸濹濼瀁濸濷 濼瀁 濷濸瀇濴濼濿 瀇瀂 瀃瀅濸瀉濸瀁瀇 濵濼濴瀆濸瀆 濶濴瀈瀆濸濷 濵瀌 瀈瀁濶濿濸濴瀅 
濷濸濹濼瀁濼瀇濼瀂瀁瀆 濴瀁濷 濻濴瀁濷濿濼瀁濺 瀀濸瀇濻瀂濷瀆 瀂濹 瀇濻濸 瀀濼瀆瀆濼瀁濺 濷濴瀇濴 濷瀈瀅濼瀁濺 
瀇濻濸 濴瀁濴濿瀌瀆濼瀆 瀃瀅瀂濶濸瀆瀆. 
11.4.1 A瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 
濸瀁濷瀃瀂濼瀁瀇
……W濼瀇濻瀂瀈瀇 瀀瀈濿瀇濼瀉濴瀅濼濴瀇濸 濴濷濽瀈瀆瀇瀀濸瀁瀇, 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇瀆 瀂濹 
瀇濻濸 瀇瀊瀂 濺瀅瀂瀈瀃瀆 瀊濼濿濿 濵濸 濶瀂瀀瀃濴瀅濸濷 瀈瀆濼瀁濺 瀅濸濿濴瀇濼瀉濸 瀅濼瀆濾 (RR) 濴瀁濷 濼瀇瀆 
95% 濶瀂瀁濹濼濷濸瀁濶濸 濼瀁瀇濸瀅瀉濴濿 (95% CI) 瀇瀂 濷濸瀆濶瀅濼濵濸 瀇濻濸 濷濼濹濹濸瀅濸瀁濶濸瀆 
濵濸瀇瀊濸濸瀁 瀇濻濸 濺瀅瀂瀈瀃瀆. A濷濷濼瀇濼瀂瀁濴濿濿瀌, 濿瀂濺濼瀆瀇濼濶 瀅濸濺瀅濸瀆瀆濼瀂瀁 瀊濼濿濿 濵濸 
瀈瀆濸濷 瀇瀂 濴濷濽瀈瀆瀇 濹瀂瀅 濹濴濶瀇瀂瀅瀆 瀇濻濴瀇 瀀濴瀌 濴濹濹濸濶瀇 瀇濻濸 瀅濴瀇濸 瀂濹 瀆濸濶瀂瀁濷濴瀅瀌 
濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 (瀆瀈濶濻 濴瀆 瀇濻濸 瀅濸濿濴瀇濼瀂瀁瀆濻濼瀃 濵濸瀇瀊濸濸瀁 瀇濻濸 濿瀂瀊濸瀅 
濸濷濺濸 瀂濹 瀇濻濸 瀇瀈瀀瀂瀅 濴瀁濷 瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 瀅濸濹濿濸濶瀇濼瀂瀁, BMI, 濴濺濸, 
瀆瀈瀅濺濸瀅瀌 濷瀈瀅濴瀇濼瀂瀁, 濸瀇濶.). ……
……W濼瀇濻瀂瀈瀇 瀃濸瀅濹瀂瀅瀀濼瀁濺 瀀瀈濿瀇濼瀉濴瀅濼濴瀇濸 濴濷濽瀈瀆瀇瀀濸瀁瀇, 瀇濻濸 瀃瀅濼瀀濴瀅瀌 
濸瀁濷瀃瀂濼瀁瀇瀆 瀂濹 瀇濻濸 瀇瀊瀂 濺瀅瀂瀈瀃瀆 瀊濼濿濿 濵濸 濶瀂瀀瀃濴瀅濸濷 濼瀁 瀇濻濸 ITT 
濴瀁濴濿瀌瀆濼瀆 瀆濸瀇, PPA 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇, 濴瀁濷 ATA 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇 瀅濸瀆瀃濸濶瀇濼瀉濸濿瀌. 
T濻濸 濴濵瀆瀂濿瀈瀇濸 瀅濼瀆濾 濷濼濹濹濸瀅濸瀁濶濸瀆 濴瀁濷 瀇濻濸濼瀅 95% 濶瀂瀁濹濼濷濸瀁濶濸 濼瀁瀇濸瀅瀉濴濿瀆 
(95% CI) 瀊濼濿濿 濵濸 瀈瀆濸濷 瀇瀂 濷濸瀆濶瀅濼濵濸 瀇濻濸 濷濼濹濹濸瀅濸瀁濶濸瀆 濵濸瀇瀊濸濸瀁 瀇濻濸 
瀇瀊瀂 濺瀅瀂瀈瀃瀆. I瀁 濴濷濷濼瀇濼瀂瀁, 濼瀁 瀇濻濸 PPA 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇, 瀇濻濸 濶濻濼 - 
瀆瀄瀈濴瀅濸 瀇濸瀆瀇 瀂瀅 F濼瀆濻濸瀅'瀆 濸瀋濴濶瀇 瀇濸瀆瀇 瀊濼濿濿 濵濸 瀈瀆濸濷 瀇瀂 濴瀁濴濿瀌瀍濸 瀇濻濸 
瀉濴瀅濼濴濵濿濸瀆 瀅濸濿濴瀇濸濷 瀇瀂 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇. M瀈濿瀇濼瀉濴瀅濼濴瀇濸 濿瀂濺濼瀆瀇濼濶 
瀅濸濺瀅濸瀆瀆濼瀂瀁 瀊濼濿濿 濵濸 瀈瀆濸濷 瀇瀂 濴濷濽瀈瀆瀇 濹瀂瀅 濹濴濶瀇瀂瀅瀆 瀇濻濴瀇 瀀濴瀌 濴濹濹濸濶瀇 瀇濻濸 
瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇 濴瀁濷 瀇瀂 濴瀁濴濿瀌瀍濸 瀇濻濸 濼瀁濷濸瀃濸瀁濷濸瀁瀇 瀅濼瀆濾 濹濴濶瀇瀂瀅瀆 
濼瀁濹濿瀈濸瀁濶濼瀁濺 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇. D瀈瀅濼瀁濺 瀇濻濼瀆 瀃瀅瀂濶濸瀆瀆, 
濶瀂瀁瀇濼瀁瀈瀂瀈瀆 瀉濴瀅濼濴濵濿濸瀆 瀊濼濿濿 濵濸 濶瀂瀁瀉濸瀅瀇濸濷 濼瀁瀇瀂 濶濴瀇濸濺瀂瀅濼濶濴濿 
瀉濴瀅濼濴濵濿濸瀆. T濻濸 瀉濴瀅濼濴濵濿濸瀆 瀈瀆濸濷 濹瀂瀅 濴濷濽瀈瀆瀇瀀濸瀁瀇 濼瀁濶濿瀈濷濸 瀇濻濸 瀃濴瀇濼濸瀁瀇 
濺瀅瀂瀈瀃濼瀁濺 (濵濿濴濷濷濸瀅 瀇瀅濴濼瀁濼瀁濺/濷濼瀅濸濶瀇 瀅濸瀀瀂瀉濴濿), 瀇瀈瀀瀂瀅 濿瀂濶濴瀇濼瀂瀁 (瀇濻濸 
濿瀂瀊濸瀅 濵瀂瀅濷濸瀅 瀂濹 瀇濻濸 瀇瀈瀀瀂瀅 濼瀆 濴濵瀂瀉濸 瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 
瀅濸濹濿濸濶瀇濼瀂瀁/瀇濻濸 濿瀂瀊濸瀅 濵瀂瀅濷濸瀅 瀂濹 瀇濻濸 瀇瀈瀀瀂瀅 濼瀆 濵濸濿瀂瀊 瀇濻濸 
瀃濸瀅濼瀇瀂瀁濸濴濿 瀅濸濹濿濸濶瀇濼瀂瀁), 濺濸瀁濷濸瀅 (瀀濴濿濸/濹濸瀀濴濿濸), 濴瀁濷 濴濺濸 (≤65 
瀌濸濴瀅瀆/>65 瀌濸濴瀅瀆) 濼瀁 瀇濻濸 PPA 濷濴瀇濴瀆濸瀇. B濸瀆濼濷濸瀆 瀇濻濸 濴濵瀂瀉濸 - 
瀀濸瀁瀇濼瀂瀁濸濷 瀉濴瀅濼濴濵濿濸瀆, 瀉濴瀅濼濴濵濿濸瀆 瀊濼瀇濻 濴 瀃 - 瀉濴濿瀈濸 < 0.1 濼瀁 瀇濻濸 
瀈瀁濼瀉濴瀅濼濴瀇濸 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 濴濿瀆瀂 濵濸 濼瀁濶濿瀈濷濸濷.……
T濻濸 瀅濸瀉濼瀆濸濷 瀃瀅瀂瀇瀂濶瀂濿 濸瀀瀃濿瀂瀌瀆 A濵瀆瀂濿瀈瀇濸 R濼瀆濾 D濼濹濹濸瀅濸瀁濶濸瀆 瀇瀂 
瀀瀂瀅濸 濷濼瀅濸濶瀇濿瀌 瀅濸濹濿濸濶瀇 瀇濻濸 濴濵瀆瀂濿瀈瀇濸 濷濼濹濹濸瀅濸瀁濶濸瀆 濼瀁 濼瀁濶濼濷濸瀁濶濸 瀅濴瀇濸瀆. 
T濻濸 瀁濸瀊 瀃瀅瀂瀇瀂濶瀂濿 濹瀈瀅瀇濻濸瀅 濶濿濴瀅濼濹濼濸瀆 瀇濻濸 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇瀆 濹瀂瀅 瀇濻濸 
瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇 濴瀁濷 瀇濻濸 濴瀁濴濿瀌瀆濼瀆 瀆濸瀇瀆 濹瀂瀅 瀇濻濸 瀀瀈濿瀇濼瀉濴瀅濼濴瀇濸 
濴瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇. I瀇 濴濿瀆瀂 瀆瀇濼瀃瀈濿濴瀇濸瀆 瀇濻濸 濶瀅濼瀇濸瀅濼濴 
濹瀂瀅 瀉濴瀅濼濴濵濿濸瀆 瀇瀂 濵濸 濼瀁濶濿瀈濷濸濷 濼瀁 瀇濻濸 瀀瀈濿瀇濼瀉濴瀅濼濴瀇濸 濴瀁濴濿瀌瀆濼瀆. T濻濸瀆濸 
瀀濸濴瀆瀈瀅濸瀆 濴瀅濸 濴濼瀀濸濷 濴瀇 濴瀉瀂濼濷濼瀁濺 濵濼濴瀆濸瀆 瀇濻濴瀇 瀀濴瀌 濴瀅濼瀆濸 濹瀅瀂瀀 瀇濻濸 
濿濴濶濾 瀂濹 濴 瀃瀅濸-濷濸濹濼瀁濸濷 瀆瀇濴瀇濼瀆瀇濼濶濴濿 濴瀁濴濿瀌瀆濼瀆 瀃濿濴瀁. 
11.4.2 S濸瀁瀆濼瀇濼瀉濼瀇瀌 A瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 
P瀅濼瀀濴瀅瀌 E瀁濷瀃瀂濼瀁瀇
濴濷濷 瀆濸濶瀇濼瀂瀁 "11.4.2 S濸瀁瀆濼瀇濼瀉濼瀇瀌 A瀁濴濿瀌瀆濼瀆 瀂濹 瀇濻濸 P瀅濼瀀濴瀅瀌 E瀁濷瀃瀂濼瀁瀇"
S濼瀁濶濸 瀇濻濸瀅濸 瀀濴瀌 濵濸 瀀濼瀆瀆濼瀁濺 瀉濴濿瀈濸瀆 濹瀂瀅 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇 瀂瀅 
瀃瀂瀆濼瀇濼瀉濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇 濸瀉濸瀁瀇瀆 濶濴瀈瀆濸濷 濵瀌 瀁瀂瀁-瀈瀅濼瀁濴瀅瀌 
瀅濸瀇濸瀁瀇濼瀂瀁 瀅濸濴瀆瀂瀁瀆, 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濸瀆 濴瀅濸 濴濷濷濸濷 瀇瀂 濸瀁瀆瀈瀅濸 瀇濻濸 
瀅瀂濵瀈瀆瀇瀁濸瀆瀆 瀂濹 瀇濻濸 濴瀁濴濿瀌瀆濼瀆 瀅濸瀆瀈濿瀇瀆.
11.4.3 A瀁濴濿瀌瀆濼瀆 瀂濹 瀆濸濶瀂瀁濷濴瀅瀌 
濸瀁濷瀃瀂濼瀁瀇瀆
W濸 瀊濼濿濿 濶瀂瀁瀆濼濷濸瀅 瀈瀆濼瀁濺 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濼瀆 瀇瀂 濸瀋瀃濿濴濼瀁 瀇濻濸 濼瀀瀃濴濶瀇 
瀂濹 瀀濼瀆瀆濼瀁濺 濷濴瀇濴 瀂瀁 瀂瀉濸瀅濴濿濿 瀅濸瀆瀈濿瀇瀆.
M濼瀆瀆濼瀁濺 瀉濴濿瀈濸瀆 瀂濹 瀇濻濸 瀆濸濶瀂瀁濷濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇瀆 瀊濼濿濿 瀁瀂瀇 濵濸 濼瀀瀃瀈瀇濸濷, 
瀁瀂瀅 瀊濼濿濿 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濸瀆 濵濸 濶瀂瀁濷瀈濶瀇濸濷 濹瀂瀅 瀇濻濸瀀. 
T濻濸 瀆濸濶瀂瀁濷濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇瀆 濴瀅濸 瀁瀂瀇 瀇濻濸 瀀濴濼瀁 瀅濸瀆濸濴瀅濶濻 瀂濵濽濸濶瀇濼瀉濸瀆. 
I瀇 濼瀆 濶濿濸濴瀅濿瀌 瀆瀇濴瀇濸濷 瀇濻濴瀇 瀁瀂 濼瀀瀃瀈瀇濴瀇濼瀂瀁 瀂瀅 瀆濸瀁瀆濼瀇濼瀉濼瀇瀌 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 
濵濸 濶瀂瀁濷瀈濶瀇濸濷 濹瀂瀅 瀇濻濸瀀. 
11.4.4 S瀈濵濺瀅瀂瀈瀃 濴瀁濴濿瀌瀆濼瀆
W濸 瀊濼濿濿 濸瀋瀃濿瀂瀅濸 濷濼濹濹濸瀅濸瀁濶濸瀆 濼瀁 瀇濻濸 瀅濴瀇濸 瀂濹 瀆濸濶瀂瀁濷濴瀅瀌 
濶濴瀇濻濸瀇濸瀅濼瀍濴瀇濼瀂瀁 濵濸瀇瀊濸濸瀁 瀇濻濸 瀇瀊瀂 濺瀅瀂瀈瀃瀆 濼瀁 濷濼濹濹濸瀅濸瀁瀇 瀆瀈濵濺瀅瀂瀈瀃瀆 
瀇濻瀅瀂瀈濺濻 瀆瀈濵濺瀅瀂瀈瀃 濴瀁濴濿瀌瀆濼瀆. S瀈濵濺瀅瀂瀈瀃瀆 濼瀁濶濿瀈濷濸 S濸瀋 (瀀濴濿濸; 
濹濸瀀濴濿濸), 濴濺濸 (≤65 瀌濸濴瀅瀆; >65 瀌濸濴瀅瀆), ASA 濶濿濴瀆瀆濼濹濼濶濴瀇濼瀂瀁 (≤II; ≥
III), BMI (≥28 濾濺/瀀²; <28 濾濺/瀀²), 瀇濻濸 瀅濸濿濴瀇濼瀂瀁瀆濻濼瀃 濵濸瀇瀊濸濸瀁 瀇濻濸 
濿瀂瀊濸瀅 濸濷濺濸 瀂濹 瀇濻濸 瀇瀈瀀瀂瀅 濴瀁濷 瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 瀅濸濹濿濸濶瀇濼瀂瀁 (濴濵瀂瀉濸 
瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 瀅濸濹濿濸濶瀇濼瀂瀁; 濵濸濿瀂瀊 瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 瀅濸濹濿濸濶瀇濼瀂瀁), 
O瀃濸瀅濴瀇濼瀁濺 瀇濼瀀濸 (≤180 瀀濼瀁瀆; >180 瀀濼瀁瀆), 瀁濸瀂濴濷濽瀈瀉濴瀁瀇 瀇濻濸瀅濴瀃瀌 
Y濸瀆, N瀂), 濴瀁濷 瀆瀈瀅濺濼濶濴濿 瀃瀅瀂濶濸濷瀈瀅濸瀆 (LAR 瀆瀈瀅濺濸瀅瀌; APR 瀆瀈瀅濺濸瀅瀌; 
T濴TME 瀆瀈瀅濺濸瀅瀌; B濴濶瀂瀁 瀆瀈瀅濺濸瀅瀌; ISR 瀆瀈瀅濺濸瀅瀌; CAA 瀆瀈瀅濺濸瀅瀌).
W濸 瀊濼濿濿 濸瀋瀃濿瀂瀅濸 瀇濻濸 濷濼濹濹濸瀅濸瀁濶濸瀆 濼瀁 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇瀆 
濵濸瀇瀊濸濸瀁 瀇濻濸 瀇瀊瀂 濺瀅瀂瀈瀃瀆 濼瀁 濷濼濹濹濸瀅濸瀁瀇 瀆瀈濵濺瀅瀂瀈瀃瀆 瀇濻瀅瀂瀈濺濻 
瀆瀈濵濺瀅瀂瀈瀃 濴瀁濴濿瀌瀆濼瀆. T濻濸 瀆瀈濵濺瀅瀂瀈瀃瀆 濼瀁濶濿瀈濷濸 濺濸瀁濷濸瀅 (瀀濴濿濸; 
濹濸瀀濴濿濸), 濴濺濸 (≤65 瀌濸濴瀅瀆 瀂濿濷; > 65 瀌濸濴瀅瀆 瀂濿濷), 瀇濻濸 瀅濸濿濴瀇濼瀂瀁瀆濻濼瀃 
濵濸瀇瀊濸濸瀁 瀇濻濸 濿瀂瀊濸瀅 瀃濴瀅瀇 瀂濹 瀇濻濸 瀇瀈瀀瀂瀅 濴瀁濷 瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 
瀅濸濹濿濸濶瀇濼瀂瀁 (濴濵瀂瀉濸 瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 瀅濸濹濿濸濶瀇濼瀂瀁; 濵濸濿瀂瀊 瀇濻濸 瀃濸瀅濼瀇瀂瀁濸濴濿 
瀅濸濹濿濸濶瀇濼瀂瀁), 濴瀆 瀊濸濿濿 濴瀆 瀂瀇濻濸瀅 瀉濴瀅濼濴濵濿濸瀆 瀇濻濴瀇 濴瀅濸 濼瀁濷濸瀃濸瀁濷濸瀁瀇濿瀌 
瀅濸濿濴瀇濸濷 瀇瀂 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇 濼瀁 瀇濻濸 瀀瀈濿瀇濼瀉濴瀅濼濴瀇濸 濴瀁濴濿瀌瀆濼瀆. 
T濻濸 瀂濵濽濸濶瀇濼瀉濸瀆 瀂濹 瀇濻濸 瀆瀈濵濺瀅瀂瀈瀃 濴瀁濴濿瀌瀆濼瀆, 瀇濻濸 濶瀅濼瀇濸瀅濼濴 濹瀂瀅 
瀆瀈濵濺瀅瀂瀈瀃 濶濿濴瀆瀆濼濹濼濶濴瀇濼瀂瀁, 濴瀁濷 瀊濻濼濶濻 瀉濴瀅濼濴濵濿濸瀆 濴瀅濸 濸濿濼濺濼濵濿濸 濹瀂瀅 
瀆瀈濵濺瀅瀂瀈瀃 濴瀁濴濿瀌瀆濼瀆 濻濴瀉濸 濵濸濸瀁 瀅濸濷濸濹濼瀁濸濷. T濻濼瀆 濼瀆 瀇瀂 濴瀉瀂濼濷 
濶瀂瀁濷瀈濶瀇濼瀁濺 瀆瀈濵濺瀅瀂瀈瀃 濴瀁濴濿瀌瀆濼瀆 瀂瀁 瀈瀁瀁濸濶濸瀆瀆濴瀅瀌 瀉濴瀅濼濴濵濿濸瀆. 
……A濷濷濼瀇濼瀂瀁濴濿濿瀌, 瀊濸 瀊濼濿濿 濶瀂瀁濷瀈濶瀇 濸瀋瀃濿瀂瀅濴瀇瀂瀅瀌 瀆瀈濵濺瀅瀂瀈瀃 濴瀁濴濿瀌瀆濸瀆 
濹瀂瀅 瀆瀂瀀濸 濾濸瀌 瀆濸濶瀂瀁濷濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇瀆, 瀆瀈濶濻 濴瀆 瀇濻濸 濼瀁濶濼濷濸瀁濶濸 瀂濹 
瀈瀅濼瀁濴瀅瀌 瀇瀅濴濶瀇 濼瀁濹濸濶瀇濼瀂瀁瀆.
A濿濿 濻瀌瀃瀂瀇濻濸瀆濼瀆 瀇濸瀆瀇瀆 濴瀅濸 瀇瀊瀂-瀆濼濷濸濷 瀊濼瀇濻 濴 瀆濼濺瀁濼濹濼濶濴瀁濶濸 濿濸瀉濸濿 瀂濹 
5%. W濸 瀊濼濿濿 濴瀁濴濿瀌瀍濸 瀇濻濸 瀅濸瀆瀈濿瀇瀆 濴瀁濷 瀊瀅濼瀇濸 瀇濻濸 瀃濴瀃濸瀅 濴濹瀇濸瀅 濴濿濿 
濸瀁瀅瀂濿濿濸濷 瀃濴瀇濼濸瀁瀇瀆 濻濴瀉濸 濶瀂瀀瀃濿濸瀇濸濷 瀇濻濸 瀂瀁濸-瀀瀂瀁瀇濻 濹瀂濿濿瀂瀊-瀈瀃.
濷濸濿濸瀇濸 瀇濻濸瀆濸 瀆瀇濴瀇濸瀀濸瀁瀇
W濸 瀀瀂瀉濸 瀇濻濸瀆濸 瀆瀇濴瀇濸瀀濸瀁瀇 瀇瀂 瀆濸濶瀇濼瀂瀁 "11.5 E瀋瀃濿瀂瀅濴瀇瀂瀅瀌 
A瀁濴濿瀌瀆濼瀆"
11.5 E瀋瀃濿瀂瀅濴瀇瀂瀅瀌 A瀁濴濿瀌瀆濼瀆
濴濷濷 瀆濸濶瀇濼瀂瀁 "11.5 E瀋瀃濿瀂瀅濴瀇瀂瀅瀌 A瀁濴濿瀌瀆濼瀆"
T濻濸 瀁濸瀊 瀃瀅瀂瀇瀂濶瀂濿 濶濿濴瀅濼濹濼濸瀆 瀇濻濸 瀇濴瀅濺濸瀇 瀂濵濽濸濶瀇瀆 濴瀁濷 濴瀁濴濿瀌瀆濼瀆 
瀀濸瀇濻瀂濷瀆 瀂濹 瀇濻濸 濸瀋瀃濿瀂瀅濴瀇瀂瀅瀌 濴瀁濴濿瀌瀆濼瀆. 
11.7 F濼瀁濴濿 濴瀁濴濿瀌瀆濼瀆
A濷濷 瀇濻濸 濶瀂瀁瀇濸瀁瀇: "T濻濸 瀅濸瀆瀈濿瀇瀆 瀂濹 瀇濻濸 濸瀋瀃濿瀂瀅濴瀇瀂瀅瀌 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 濵濸 
瀃瀈濵濿濼瀆濻濸濷 瀆濸瀃濴瀅濴瀇濸濿瀌 濴瀆 濴 瀃瀂瀆瀇-濻瀂濶 濴瀁濴濿瀌瀆濼瀆." 
T濻濸 瀅濸瀃瀂瀅瀇濼瀁濺 瀇濼瀀濸 濹瀂瀅 瀇濻濸 濸瀋瀃濿瀂瀅濴瀇瀂瀅瀌 濴瀁濴濿瀌瀆濼瀆 濻濴瀆 濵濸濸瀁 
瀆瀈瀃瀃濿濸瀀濸瀁瀇濸濷.
12.1 C濴瀆濸 R濸瀃瀂瀅瀇 F瀂瀅瀀/E濿濸濶瀇瀅瀂瀁濼濶 
D濴瀇濴 R濸濶瀂瀅濷濼瀁濺
A濷濷 瀇濻濸 濶瀂瀁瀇濸瀁瀇: “A濿濿 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 瀀濸濸瀇 瀇濻濸 濼瀁濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴 
瀊濼濿濿 濵濸 瀅濸濺濼瀆瀇濸瀅濸濷. F瀂瀅 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 濴瀅濸 濸瀋濶濿瀈濷濸濷 濷瀈濸 瀇瀂 瀇濻濸 
濸瀋濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴, 瀇濻濸 瀆瀃濸濶濼濹濼濶 瀅濸濴瀆瀂瀁瀆 濹瀂瀅 濸瀋濶濿瀈瀆濼瀂瀁 瀁濸濸濷 瀇瀂 濵濸 
瀅濸濶瀂瀅濷濸濷. F瀂瀅 瀇濻濸 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 濸瀉濸瀁瀇瀈濴濿濿瀌 濸瀁瀇濸瀅 瀇濻濸 
瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 瀃瀅瀂濶濸瀆瀆, 瀇濻濸濼瀅 濷濸瀇濴濼濿濸濷 濼瀁濹瀂瀅瀀濴瀇濼瀂瀁 瀊濼濿濿 濵濸 
瀅濸濺濼瀆瀇濸瀅濸濷 濼瀁 瀇濻濸 濷濴瀇濴濵濴瀆濸. F瀂瀅 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 濷濸瀉濼濴瀇濸 濹瀅瀂瀀 瀇濻濸 
瀅濴瀁濷瀂瀀濼瀍濸濷 濺瀅瀂瀈瀃濼瀁濺 濹瀂瀅 瀉濴瀅濼瀂瀈瀆 瀅濸濴瀆瀂瀁瀆 濴瀁濷 瀇濻瀂瀆濸 瀊濻瀂 
濷濸瀉濼濴瀇濸 濹瀅瀂瀀 瀇濻濸 濸瀆瀇濴濵濿濼瀆濻濸濷 濼瀁瀇濸瀅瀉濸瀁瀇濼瀂瀁 瀃瀅瀂濶濸瀆瀆 濷瀈瀅濼瀁濺 瀇濻濸 
濼瀁瀇濸瀅瀉濸瀁瀇濼瀂瀁, 瀇濻濸 瀅濸濴瀆瀂瀁瀆 濹瀂瀅 瀇濻濸 濷濸瀉濼濴瀇濼瀂瀁 瀁濸濸濷 瀇瀂 濵濸 
瀅濸濶瀂瀅濷濸濷. A濿濿 瀃濴瀇濼濸瀁瀇瀆 濴濹瀇濸瀅 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 濴瀅濸 瀅濸瀄瀈濼瀅濸濷 瀇瀂 
瀅濸濶瀂瀅濷 瀇濻濸 瀅濸濿濸瀉濴瀁瀇 濷濴瀇濴 濶瀂瀀瀃濿濸瀇濸濿瀌 濼瀁 濴濶濶瀂瀅濷濴瀁濶濸 瀊濼瀇濻 瀇濻濸 
濶瀂瀁瀇濸瀁瀇 瀂濹 瀇濻濸 CRF. ”
T濻濸 瀁濸瀊 瀅濸瀆濸濴瀅濶濻 瀃瀅瀂瀇瀂濶瀂濿 濶濿濴瀅濼濹濼濸瀆 瀇濻濸 瀆濶瀂瀃濸 瀂濹 濷濴瀇濴 
瀅濸濶瀂瀅濷濼瀁濺, 濴瀆 瀊濸濿濿 濴瀆 瀇濻濸 瀃瀅濼瀁濶濼瀃濿濸瀆 濹瀂瀅 濻濴瀁濷濿濼瀁濺 瀅濸濿濸瀉濴瀁瀇 濷濴瀇濴 
瀊濻濸瀁 瀃濴瀇濼濶濼瀃濴瀁瀇瀆 濷濸瀉濼濴瀇濸 濹瀅瀂瀀 瀇濻濸 瀅濸瀆濸濴瀅濶濻 瀃瀅瀂瀇瀂濶瀂濿. 
12.2 D濴瀇濴 瀀濴瀁濴濺濸瀀濸瀁瀇
A濿濿 瀃濴瀇濼濸瀁瀇瀆 瀊濻瀂 瀀濸濸瀇 瀇濻濸 濼瀁濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴 瀊濼濿濿 濵濸 瀅濸濶瀂瀅濷濸濷. I濹 濴 
瀃濴瀇濼濸瀁瀇 濼瀆 濸瀋濶濿瀈濷濸濷 濷瀈濸 瀇瀂 濸瀋濶濿瀈瀆濼瀂瀁 濶瀅濼瀇濸瀅濼濴 瀂瀅 濼瀆 瀊濼瀇濻濷瀅濴瀊瀁 
濴濹瀇濸瀅 瀅濴瀁濷瀂瀀濼瀍濴瀇濼瀂瀁 濷瀈濸 瀇瀂 瀊濼瀇濻濷瀅濴瀊濴濿 濶瀅濼瀇濸瀅濼濴, 瀇濻濼瀆 瀀瀈瀆瀇 濵濸 
濷瀂濶瀈瀀濸瀁瀇濸濷 濼瀁 瀇濻濸 濷濴瀇濴濵濴瀆濸.
濷濸濿濸瀇濸 瀇濻濼瀆 瀃濴瀅濴濺瀅濴瀃濻
T濻濼瀆 瀃濴瀅瀇 濷瀂濸瀆 瀁瀂瀇 濹濴濿濿 瀊濼瀇濻濼瀁 瀇濻濸 瀆濶瀂瀃濸 瀂濹 瀇濻濸 濶瀂瀁瀇濸瀁瀇 瀂濹 瀇濻濸 
"D濴瀇濴 M濴瀁濴濺濸瀀濸瀁瀇" 瀆濸濶瀇濼瀂瀁. T濻濸 濶瀂瀅瀅濸瀆瀃瀂瀁濷濼瀁濺 濷濸瀆濶瀅濼瀃瀇濼瀂瀁 
濻濴瀆 濵濸濸瀁 瀅濸瀉濼瀆濸濷 濴瀁濷 濴濷濷濸濷 瀇瀂 "12.1 C濴瀆濸 R濸瀃瀂瀅瀇 
F瀂瀅瀀/E濿濸濶瀇瀅瀂瀁濼濶 D濴瀇濴 R濸濶瀂瀅濷濼瀁濺". 
17. I瀁瀆瀈瀅濴瀁濶濸 濴瀁濷 濶瀂瀀瀃濸瀁瀆濴瀇濼瀂瀁.
A濷濷 瀇濻濸 濶瀂瀁瀇濸瀁瀇: "F瀂瀅 濸濴濶濻 瀃濴瀇濼濸瀁瀇 濸瀁瀅瀂濿濿濸濷 濼瀁 瀇濻濸 瀇瀅濼濴濿, 濴瀁 
濸瀁瀅瀂濿濿瀀濸瀁瀇 濶瀂瀀瀃濸瀁瀆濴瀇濼瀂瀁 瀂濹 100 瀌瀈濴瀁 瀊濼濿濿 濵濸 瀃瀅瀂瀉濼濷濸濷 瀇瀂 
濸瀁濻濴瀁濶濸 瀇濻濸 瀃濴瀇濼濸瀁瀇'瀆 濶瀂瀀瀃濿濼濴瀁濶濸. "
M濸濴瀆瀈瀅濸瀆 瀇瀂 濹瀈瀅瀇濻濸瀅 瀅濸濷瀈濶濸 瀇濻濸 濿瀂瀆瀆 瀇瀂 濹瀂濿濿瀂瀊 - 瀈瀃
18. P瀈濵濿濼濶濴瀇濼瀂瀁 瀆瀇濴瀇濸瀀濸瀁瀇
A濷濷 瀇濻濸 濶瀂瀁瀇濸瀁瀇: "T濻濸 瀅濸瀆瀈濿瀇瀆 瀂濹 瀇濻濸 濸瀋瀃濿瀂瀅濴瀇瀂瀅瀌 濴瀁濴濿瀌瀆濼瀆 瀊濼濿濿 濵濸 
瀃瀈濵濿濼瀆濻濸濷 瀆濸瀃濴瀅濴瀇濸濿瀌 濴瀆 濴 瀃瀂瀆瀇-濻瀂濶 濴瀁濴濿瀌瀆濼瀆 濴濹瀇濸瀅 瀇濻濸 
瀃瀈濵濿濼濶濴瀇濼瀂瀁 瀂濹 瀇濻濸 瀅濸瀆瀈濿瀇瀆 瀂濹 瀇濻濸 瀃瀅濼瀀濴瀅瀌 濸瀁濷瀃瀂濼瀁瀇. "
T濻濸 瀃瀈濵濿濼濶濴瀇濼瀂瀁 瀇濼瀀濸 濴瀁濷 瀆濶瀂瀃濸 瀂濹 瀇濻濸 瀅濸瀆濸濴瀅濶濻 - 瀅濸濿濴瀇濸濷 
瀅濸瀆瀈濿瀇瀆 濻濴瀉濸 濵濸濸瀁 瀆瀈瀃瀃濿濸瀀濸瀁瀇濸濷.
A瀃瀃濸瀁濷濼瀋 2: ICIQ-SF S濶瀂瀅濸
T濻濸 濺瀅濴濷濼瀁濺 瀂濹 瀈瀅濼瀁濴瀅瀌 濼瀁濶瀂瀁瀇濼瀁濸瀁濶濸 濻濴瀆 濵濸濸瀁 瀆瀈瀃瀃濿濸瀀濸瀁瀇濸濷:
- T瀂瀇濴濿 瀆濶瀂瀅濸 瀂濹 0 - 5: N瀂 瀈瀅濼瀁濴瀅瀌 濼瀁濶瀂瀁瀇濼瀁濸瀁濶濸 瀂瀅 瀀濼濿濷 瀈瀅濼瀁濴瀅瀌 
濼瀁濶瀂瀁瀇濼瀁濸瀁濶濸.
- T瀂瀇濴濿 瀆濶瀂瀅濸 瀂濹 6 - 10: M瀂濷濸瀅濴瀇濸 瀈瀅濼瀁濴瀅瀌 濼瀁濶瀂瀁瀇濼瀁濸瀁濶濸.
- T瀂瀇濴濿 瀆濶瀂瀅濸 瀂濹 11 濴瀁濷 濴濵瀂瀉濸: S濸瀉濸瀅濸 瀈瀅濼瀁濴瀅瀌 濼瀁濶瀂瀁瀇濼瀁濸瀁濶濸.
T濻濼瀆 濼瀆 濶瀂瀁濷瀈濶濼瀉濸 瀇瀂 瀇濻濸 瀉濴瀅濼濴濵濿濸 瀇瀅濴瀁瀆濹瀂瀅瀀濴瀇濼瀂瀁 濴瀁濷 濺瀅濴濷濼瀁濺 
濴瀆瀆濸瀆瀆瀀濸瀁瀇 瀂濹 瀈瀅濼瀁濴瀅瀌 濼瀁濶瀂瀁瀇濼瀁濸瀁濶濸 濷瀈瀅濼瀁濺 瀆瀇濴瀇濼瀆瀇濼濶濴濿 濴瀁濴濿瀌瀆濼瀆.