Study on the Treatment of Post-stroke Dysphagia and Stroke-associated Pneumonia With Bronchoscopy
Phase: NA
Conditions: Stroke Associated Pneumonia, Non Severe Ischemic Stroke, Dysphagia
Sponsor: The First People's Hospital of Zunyi

 
Cover Page 
 
Clinical Study (No. HZ（2019）146) 
Study on Bronchoscopy for the Treatment of Post-Stroke Dysphagia and 
Stroke-Associated Pneumonia 
 
Product Name: Olympus BF-P180 Fiber Bronchoscope  
State Food and Drug Administration (Imported) Medical Device No. 2007, No. 
3221928 
Study Type: Interventional Study 
Study Center: Zunyi First People's Hospital 
 
Date: September 01, 2019 

This study will adhere to this clinical study protocol. 
Table of Contents 
Cover Page 
Table of Contents 
Study Protocol 
I. Study Background 
II. Study Objectives 
III. Study Plan 
1. Study Population Selection 
2. Subject Recruitment Number 
3. Investigator Selection Criteria 
4. Study Timeline 
5. Study Execution 
IV. Adverse Events 
1. Classification of Adverse Events and Serious Adverse Events 
2. Severity 
3. Reporting of Serious Adverse Events 
V. Ethics and Quality 
VI. Data Management 
VII. Statistical Analysis 

1. Statistical Software 
2. Data Description 
3. Data Statistics 
4. Statistical Analysis Plan 
VIII. Final Report and Publication 
IX. References 
 
 
 
 
 
 
 

Study Protocol 
I. Study Background 
Stroke-associated pneumonia (Stroke-Associated Pneumonia ,SAP) is one of 
the most common respiratory complications of acute stroke, occurring in 
approximately 4% to 9% of patients after stroke[1-4]. The incidence of SAP is 
higher in patients with acute ischemic stroke treated in neurological intensive 
care units and those requiring nasogastric tube feeding (21% and 44%, 
respectively)[5,6]. Compared to patients without pneumonia, those with SAP 
have higher mortality rates and poorer long-term outcomes[2,3]. Pneumonia is 
the most common cause of fever within 48 hours after acute stroke and the 
most frequent complication within 2-4 weeks after supratentorial ischemic 
infarction[1,7,8]. Furthermore, retrospective data indicate that pneumonia and 
respiratory diseases are the most common reasons for hospitalization among 
stroke survivors during the first five years after ischemic stroke[9]. Independent 
risk factors for in-hospital pneumonia include age greater than 65 years, 
dysarthria or absence of speech due to aphasia, severe post-stroke disability, 
cognitive impairment, and dysphagia[10]. In an early prospective study of 124 
acute stroke patients treated in the intensive care unit, risk factors were 
mechanical ventilation, abnormal chest X-ray on admission, and dysphagia[5]. 
Aspiration pneumonia after stroke is often due to stroke-related dysphagia 

(i.e., impaired motor and sensory mechanisms of swallowing) or decreased 
level of consciousness leading to impaired cough reflex and glottic closure. 
Moreover, prophylactic antibiotic use in acute stroke patients does not reduce 
the incidence of post-stroke pneumonia or improve outcomes[12,13]. 
Dysphagia is a common symptom in terminal illnesses. In the last weeks to 
months of life, declining swallowing function diminishes the desire and ability 
to eat. Difficulty swallowing solids and liquids is one of the most common 
symptoms in the final days of life[13,14]. Swallowing disorders affect quality of 
life (e.g., social interaction, communication) and lead to impaired nutrition and 
hydration. Dysphagia is also a major predisposing condition for aspiration and 
can lead to pneumonia, and in some cases, even choking or death. 
Considering the central role of food and nutrition in social interaction and the 
general concern about nutrition for health, swallowing disorders can also 
cause frustration and distress for family caregivers and healthcare staff. 
Additionally, for many patients with terminal illnesses, the inability to swallow 
and/or lack of interest in food can be a critical symptom prompting decisions 
to forgo treatment and seek end-of-life care. Dysphagia refers to difficulty 
swallowing food or liquids, including medications in liquid or pill form. Post-
stroke dysphagia (Post-Stroke Dysphagia, PSD) may arise from motor or 
sensory dysfunction in neurological processes, potentially causing problems 
with eating certain types of food or liquids, or even an inability to swallow 
altogether. Patients may complain of food sticking in the upper 

gastrointestinal tract from the throat to the distal esophagus, and experience 
coughing or choking when eating or drinking. Chronic dysphagia affects the 
efficiency of oral intake, leading to physical weakness, loss of appetite, weight 
loss, dehydration, and malnutrition. Furthermore, airway protection or 
swallowing safety can be threatened by swallowing disorders. Food or liquid 
may enter the trachea, leading to aspiration, choking, or in severe cases, 
asphyxiation. Aspiration pneumonia is an infectious process caused by the 
aspiration of oropharyngeal secretions colonized by pathogenic bacteria, with 
Gram-negative enteric bacilli and anaerobes being the most common 
causative microorganisms. Aspiration of sterile acidic gastric contents can also 
cause acute chemical injury to the lungs. 
Therefore, improving post-stroke dysphagia is particularly important for 
treating SAP, as it addresses the underlying cause, significantly reduces the 
incidence of SAP, and improves outcomes. Swallowing is not a voluntary act 
but a complex reflex that requires specific stimuli to initiate. Although the 
swallowing action can be started voluntarily, its completion is a complex 
reflex. A single simple swallow requires the coordination of 25 pairs of muscles 
in the oral cavity, pharynx, larynx, esophagus, and face, involving at least 6 
pairs of cranial nerves, the speech system, and the respiratory system. 
Swallowing is a typical, complex reflex action consisting of a sequence of 
interlinked stages, each composed of a series of processes, where the activity 
of one stage can trigger the next. Receptors for swallowing are located in the 

soft palate, posterior pharyngeal wall, epiglottis, esophagus, etc. Afferent 
nerves include fibers from the soft palate (Cranial Nerves V, IX), posterior 
pharyngeal wall (CN IX), epiglottis (CN X), and esophagus (CN X). The central 
pattern generator is located in the medulla oblongata. Efferent nerves are in 
Cranial Nerves V, IX, X, XI, and XII, and the effector organs include the tongue, 
larynx, pharyngeal muscles, esophageal muscle groups, etc. Every stage of 
swallowing is interconnected and indispensable. After a stroke, if the lesion 
involves the medulla oblongata, swallowing and breathing difficulties can 
occur. 
Domestic research has primarily focused on the prevention of SAP-related risk 
factors, bundled care, rehabilitation training, and traditional Chinese medicine 
acupuncture, with a lack of reports on bronchoscopy for treating post-stroke 
dysphagia. Bedside bronchoscopy can clear airway secretions, pass directly 
through the glottis, stimulate cough and swallowing muscles to produce 
contractions, playing a positive role in preventing aspiration and alleviating 
dysphagia. Bronchoscopy can directly stimulate the trigeminal nerve in the 
soft palate, the glossopharyngeal nerve in the posterior pharyngeal wall, and 
the vagus nerve in the epiglottis, promoting contraction of the masticatory 
muscles, suprahyoid muscles, infrahyoid muscles, facial muscles, tongue 
muscles, and soft palate muscles, thereby training the swallowing muscle 
groups, exercising swallowing function, improving swallowing disorders, and 
significantly reducing the incidence and mortality rate of SAP. 

Currently, there are no reports domestically or internationally on bedside 
bronchoscopy for the treatment of post-stroke dysphagia and SAP. This study 
aims to explore the application value and clinical safety of portable fiber 
bronchoscopy in non-severe SAP patients with dysphagia, and to evaluate 
whether bronchoscopic treatment can alleviate dysphagia symptoms, improve 
hypoxia, pulmonary infection, and SAP prognosis. 
II. Study Objectives 
Primary Objective: To observe the efficacy of bronchoscopic sputum 
suction + lavage therapy on post-stroke dysphagia and stroke-associated 
pneumonia. 
Secondary Objectives: To compare National Institutes of Health Stroke 
Scale(NIHSS scores)( It is a standardized tool used to assess the degree of 
neurological deficits in patients with acute stroke, consisting of 15 items 
covering consciousness level, visual field, facial paralysis, limb movement, 
ataxia, sensory, language, and articulation disorders. The scoring range for 
each project is 0 to 4 points, with 0 indicating no defects and higher scores 
indicating more severe neurological deficits; The total score ranges from 0 to 
42 points, with 0 indicating no neurological deficits and 42 indicating 
extremely severe deficits), Acute Physiology and Chronic Health Evaluation 
(APACHE) II scores(It includes three parts: acute physiology score (APS), 
chronic physiology score (CPS), and patient age score, with a total score of 0-

71 points. The higher the score, the more severe the patient's condition, the 
worse the prognosis, and the higher the mortality rate), CPIS scores (Clinical 
Pulmonary Infection Scores), Water Swallow Test scores(Grade I: able to drink 
without coughing within 5 seconds; Grade II: No coughing after drinking twice 
or more; Grade III: Can be consumed in one go but accompanied by coughing; 
Grade IV: Drink twice or more with coughing; Grade V: Frequent coughing and 
inability to finish all drinks. Grade I indicates normal, Grade II indicates 
suspicious, and Grade III or above indicates abnormal), C-reactive protein 
(CRP), Length of hospital stay, arterial partial pressure of oxygen (PaO2), 
Height(m), Weight(Kg),Body Mass Index（BMI, Report BMI in kg/m ^ 2 by 
combining weight and height）,and overall clinical treatment efficacy between 
the two groups. 
III. Study Plan 
1. Study Population Selection 
This is a single-center, prospective, randomized, controlled clinical trial. 
The control group will receive conventional anti-infective and expectorant 
therapy, plus suction via suction catheter as needed (i.e., when dyspneic or 
when phlegm sounds are heard in the airway). The observation group will 
receive, in addition to the control group's treatment, bronchoscopic treatment 
1-2 times, including sputum suction under endoscopy, lavage, and drug 

instillation. This study will enroll 60 patients with post-stroke dysphagia and 
stroke-associated pneumonia, randomly divided into an experimental group 
and a control group. 
1.1 Inclusion Criteria 
- Meets the diagnostic criteria for acute stroke and is clearly diagnosed 
through head MRI or CT examination.  
- According to the Wada drinking water test, there is indeed difficulty 
swallowing. 
- Pneumonia occurs within 72 hours after stroke, confirmed by chest imaging 
examination, and meets the diagnostic criteria for stroke-related pneumonia. 
- Clear consciousness, stable vital signs, and able to cooperate with bronchial 
examination. 
1.2 Exclusion Criteria 
- The condition is critical, with severe hemiplegia and mental disorders that 
cannot tolerate bronchoscopy treatment.  
- Combined lung tumors, open pulmonary tuberculosis, coagulation 
dysfunction, severe cardiovascular and cerebrovascular diseases, severe heart, 
liver, and kidney dysfunction, and pulmonary infection before stroke. 
- Not willing to undergo bronchoscopy examination.  

- Individuals with previous esophageal functional structural abnormalities. 
- Disagree with participating researchers. 
1.3 Withdrawal/Early Termination from Study 
If a patient discontinues the study before completing the assessments 
specified in the study protocol, they will be considered withdrawn/terminated 
early. Patients may withdraw/terminate early for any of the following reasons: 
• 
Adverse Event (AE) 
• 
Inability to complete the bronchoscopy procedure 
A final assessment of the patient should be conducted at this time, and the 
reason for early termination should be recorded on the appropriate page of 
the Case Report Form (CRF). For patients who withdraw due to an adverse 
event, the investigator must follow up with them. 
2. Subject Recruitment Number 
This single-center, prospective, randomized controlled clinical trial plans to 
enroll 60 patients. 
3. Investigator Selection Criteria 

The study center should have a standard Intensive Care Unit (ICU) with a 
sufficient volume of critically ill patients. It is planned to include 24 large 
general hospital ICUs. 
4. Study Timeline 
4.1 Study Implementation Period: September 2019 --- September 2021 
4.2 Study Observation Period: Observation for 7 days starting from 
enrollment. 
5. Study Execution 
This is a single-center, prospective, randomized, controlled, clinical study. 
5.1 Enrollment 
Before the study begins, the investigator must clearly and verbally explain the 
study's circumstances, potential risks, and benefits to the patient or their 
authorized representative. The patient or their authorized representative and 
the investigator must sign and date the informed consent form. The patient 
can only enter the screening process and subsequently participate in the study 
after signing the informed consent form. 
After signing the written informed consent, the patient will be assessed to 
determine if they meet the study criteria: 

1. Patient's medical history; 
2. Vital signs; 
5.2 Randomization and Blinding 
According to the principle of complete randomization, 60 patients will be 
assigned to the experimental group and the control group. 
5.3 Research Methods 
The control group will receive conventional anti-infective and expectorant 
therapy, plus suction via suction catheter as needed (i.e., when dyspneic or 
when phlegm sounds are heard in the airway). The observation group will 
receive, in addition to the control group's treatment, bronchoscopic treatment 
1-2 times, including sputum suction under endoscopy, lavage, and drug 
instillation. Specific procedure steps: Prepare for the bronchoscopy procedure. 
Under continuous nasal cannula oxygen and vital sign monitoring via ECG, 
administer Atropine Injection 0.5mg (National Drug Approval No. H37021468, 
Shandong Huaxin Pharmaceutical Group Co., Ltd.) combined with Lidocaine 
Injection (National Drug Approval No. H20065387, China Otsuka 
Pharmaceutical Co., Ltd.) 0.1g via nebulization for local anesthesia. Insert the 
Olympus BF-P180 fiber bronchoscope routinely through the nostril, 
sequentially entering various levels of bronchi. Under direct vision, clear 
airway secretions, collect lavage fluid for bacterial culture and drug sensitivity 
testing. If sputum is thick and difficult to suction, lavage with normal saline 

can be used. Simultaneously, select sensitive antibiotics for instillation therapy 
based on the bacterial culture results of the airway secretions. After 
completion, slowly withdraw the bronchoscope. Both groups will receive 
continuous treatment for 1 week. Throughout the process, closely monitor the 
patient's vital signs. If oxygen saturation falls below 80% or heart rate exceeds 
130 beats/min, immediately withdraw the fiber bronchoscope and provide 
symptomatic treatment. Resume the subsequent procedure after vital signs 
stabilize. 
5.4 Adverse Events 
Record adverse events, the number of and reasons for trial dropouts in detail. 
IV. Adverse Events 
1. Classification of Adverse Events and Serious Adverse Events 
Common adverse reactions during bronchoscopy include: laryngospasm, 
airway bleeding, pneumothorax, cardiac arrest, aspiration, hoarseness. 
Medical Device Adverse Event: Any harmful event unrelated to the intended 
effect of a medical device that occurs during the normal use of an approved, 
qualified medical device, leading or potentially leading to human injury. 
Among these, death and serious injury events must be reported to the 
monitoring agency. Serious injury refers to any of the following: 

① Life-threatening; 
② Resulting in permanent impairment of a body function or permanent 
damage to a body structure; 
③ Necessitating medical or surgical intervention to prevent such permanent 
impairment or damage. 
Subject Death: An event resulting in the death of a subject. 
Life-Threatening: An event which, in the investigator's judgment, places the 
subject at immediate risk of death without medical intervention. It does not 
include an event that might have caused death had it occurred in a more 
severe form. 
Hospitalization: An event resulting in admission to the hospital, regardless of 
length of stay. This does not include emergency room observation or 
outpatient clinic visits. 
Prolongation of Hospitalization: An event that results in or prolongs a 
subject's hospitalization. 
Persistent or Significant Disability/Incapacity: An event resulting in a 
condition that substantially disrupts the subject's ability to conduct normal life 
functions. This does not include relatively minor symptoms such as headache, 
nausea, vomiting, diarrhea, influenza, or accidental injury. 

Important Medical Event: An event that may not be immediately life-
threatening or result in death or hospitalization but, based on appropriate 
medical judgment, may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed above (e.g., subject 
death, life-threatening, hospitalization, prolongation of hospitalization, 
congenital anomaly, or persistent disability/incapacity). 
2. Severity 
Physicians can use the following definitions to judge the severity of all adverse 
events and serious adverse events, serving as study endpoints/data cut-off 
points. 
[Mild] The adverse event is transient, and the patient tolerates it easily. 
[Moderate] The adverse event causes discomfort to the subject and interferes 
with the subject's normal activities. 
[Severe] The adverse event significantly affects the subject's daily activities, 
may cause incapacitation, or is life-threatening. 
3. Reporting of Serious Adverse Events 
In the event of a Serious Adverse Event, regardless of whether it is related to 
the device or the control device, the physician must notify Olympus (China) 
Co., Ltd. within 24 hours of becoming aware of the event. 

V. Ethics and Quality 
Ethics committee approval will be obtained prior to the initiation of this study. 
Before enrolling a patient, authorization must be obtained for the use and/or 
disclosure of personal and/or health data. To protect patient privacy, the 
patient's age will be recorded on the Case Report Form instead of the date of 
birth, and the patient's initials will be recorded on the Case Report Form. 
The consistency of the collected Case Report Form data will be checked. Data 
queries will be issued for inconsistent data, requiring clarification by the 
physician. 
VI. Data Management 
Investigators must fill in the collected data into the Case Report Form 
according to the study protocol requirements. At the end of the study, the 
investigator will submit the Case Report Forms for all patients enrolled in this 
study to the data management center. These Case Report Forms must be 
complete and signed. The consistency of the collected Case Report Form data 
will be checked. Data queries will be issued for inconsistent data, requiring 
clarification by the physician. 
VII. Statistical Analysis 

1. Statistical Software 
The data statistical work will be completed by a biostatistician using the 
statistical software SPSS 22.0. 
2. Data Description 
Measurement data will be expressed as mean ± standard deviation (x̄  ± s), 
using normality tests and t-tests. Enumeration data will be expressed as n (%), 
using the Chi-square test (X² test). A P-value < 0.05 will be considered 
statistically significant. 
3. Data Statistics 
All hypothesis tests will be two-sided, and a P-value < 0.05 will be considered 
statistically significant. Baseline data will be evaluated for comparability 
between groups, using two-tailed statistical tests at the α=5% level. Group 
comparisons for enumeration data will use the Chi-square test, and group 
comparisons for measurement data will use the t-test. 
4. Statistical Analysis Plan 
Will be completed by professional statistical personnel. After all data entry and 
verification are completed, the statistician shall promptly complete the 
statistical analysis work and produce a written statistical analysis report. 

VIII. Final Report and Publication 
After the study concludes, the principal investigator will lead the collaboration 
with investigators from all study centers to compile the study final report. 
Investigators from all study centers will sign the study final report. The study 
report will include a description of the study objectives, the methods used in 
the study, as well as the results and conclusions. 
The Upjohn Company will archive the study final report. Without the explicit 
written consent of The Upjohn Company, investigators cannot disclose it in 
any form (publication or presentation) to unauthorized personnel. 
IX. References 
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