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Tobramycin Inhalation Solution for Pseudomonas Aeruginosa Eradication in Bronchiectasis (ERASE)

Primary Purpose

Bronchiectasis Adult, Pseudomonas Aeruginosa Infection

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Tobramycin Inhalant Product
Ciprofloxacin 750 MG
Oral ciprofloxacin placebo
Natural saline inhalation
Sponsored by
Shanghai Pulmonary Hospital, Shanghai, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bronchiectasis Adult focused on measuring bronchiectasis,, Pseudomonas Aeruginosa, eradication, inhaled antibiotics, randomized controlled trial

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female, aged 18 years and 80 years at screening Signed and dated written informed consent prior to admission to the study in accordance with local legislation. Clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections) and investigator-confirmed diagnosis of bronchiectasis by CT scan During the screening period, patients must have a positive P. aeruginosa culture in their sputum and must meet one of the following criteria: (1) they have never been isolated with P. aeruginosa from sputum or bronchoalveolar lavage fluid (BALF) before; (2) they were isolated with P. aeruginosa from sputum or BALF for the first time within 12 months before screening; (3) they had prior isolation of P. aeruginosa but not within the last 24 months (defined as having negative sputum culture results at least twice before starting antibiotic treatment) During the screening period, patients must remain clinically stable (no significant changes in respiratory symptoms and no upper respiratory tract infection or bronchiectasis exacerbations for 4 weeks) During the screening period, P. aeruginosa is not resistant to Tobramycin and Ciprofloxacin based on the drug sensitivity test of sputum culture in vitro Patient can tolerate nebulized inhalation therapy Exclusion criteria Patients who are allergic to or cannot tolerate the investigational drugs (Tobramycin, Ciprofloxacin) Patients with uncontrolled asthma, physician-diagnosed cystic fibrosis, and Current diagnosis of allergic bronchopulmonary aspergillosis, hypogammaglobulinemia, common variable immunodeficiency, mycobacterial infection (including pulmonary non-tuberculous mycobacterial disease) requiring treatment. Participants with unstable cardiovascular and cerebrovascular diseases, defined as those who have experienced clinically worsening symptoms (such as unstable angina, rapid atrial fibrillation, cerebral hemorrhage, acute cerebral infarction, etc.) or have been hospitalized due to these diseases within 90 days prior to the screening Participants with progressive or uncontrolled systemic diseases, such as those affecting the urinary, hematological, digestive, endocrine, respiratory, circulatory, nervous, or mental systems, are not suitable for this clinical trial. This is particularly the case if these conditions are evaluated by the researcher as being unstable or potentially escalating into severe conditions during the trial. AST and/or ALT >2 ULN at screening period Serum creatinine >ULN at screening period Participants with a history of hearing loss or those who are determined by the researcher to have clinically significant chronic tinnitus Participants with a history of prolonged QT intervals or those whose electrocardiograms show prolonged QT intervals during the screening period Participants who have used drugs that are prohibited according to the plan during the screening period. Women of childbearing potential adhering to contraception requirements. Patients with FEV1% of predicted value<30% Participants who have participated in other clinical trials (defined as those where medication has been administered) within the 4 weeks prior to the screening Participants who have experienced moderate or severe hemoptysis (defined as expectorating 100-500ml of blood in 24 hours for moderate hemoptysis; and expectorating more than 500ml in 24 hours, or a single instance of expectorating more than 100ml of blood for severe hemoptysis) due to bronchiectasis within the past 6 months. Participants who are deemed unsuitable for inclusion in the study due to other reasons, as determined by the researcher.

Sites / Locations

  • Ruijin Hospital
  • The Shanghai Fifth People's Hospital
  • Shanghai pulmonary hospitalRecruiting
  • The First People's Hospital of Anning City Affiliated to Kunming University of Science and Technology
  • Beijing Chao-Yang Hospital, Capital Medical University
  • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
  • Peking University Third Hospital
  • The First Affiliated Hospital of Jilin University
  • The Second Xiangya Hospital of Central South University
  • Xiangya Hospital, Central South University
  • West China Hospital of Sichuan University
  • The Second Affiliated Hospital of Chongqing Medical University
  • The Third Affiliated Hospital of Chongqing Medical University
  • The Second Affiliated Hospital of Dalian Medical University
  • Fujian Provincial Hospital
  • The First Affiliated Hospital of Guangzhou Medical University
  • The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
  • The First Affiliated Hospital of Jinan University
  • Guizhou Provincial People's Hospital
  • The Second Affiliated Hospital of Zhengjiang University
  • Anhui Chest Hospital
  • The First Affiliated Hospital of Anhui Medical University
  • Huzhou Central Hospital
  • The First Hospital of Jiaxing City
  • The Second Hospital of Jiaxing City
  • Qilu Hospital of Shandong University
  • The First Affiliated Hospital of Shandong First Medical University
  • The First Affiliated Hospital of Wenzhou Medical University
  • The First Affiliated Hospital of Nanchang University
  • Affiliated Hospital of Yifu, Nanjing Medical University
  • The First Affiliated Hospital of Guangxi Medical University
  • Affiliated Hospital, Nantong University
  • The Sixth People's Hospital of Nantong City
  • Fenghua District People's Hospital of Ningbo City
  • Ningbo Medical Center Lihuili Hospital
  • The First Affiliated Hospital of Ningbo University
  • Qingdao Municipal Hospital
  • Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine
  • Shanghai Eighth People's Hospital
  • Shanghai General Hospital
  • Shanghai Putuo District People's Hospital
  • Shanghai Shidong Hospital of Yangpu District
  • Shanghai Sixth People's Hospital
  • Shanghai Songjiang District Central Hospital
  • Shanghai Yangpu District Central Hospital
  • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Zhongshan Hospital, Fudan University
  • Shangrao People's Hospital
  • Shengjing Hospital of China Medical University
  • The First Affiliated Hospital of China Medical University
  • Shenzhen Institute of Respiratory Diseases
  • The Eighth Affiliated Hospital of Sun Yat-Sen University
  • Suzhou Science and Technology Town Hospital
  • The First Affiliated Hospital of Soochow University
  • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Union Hospital,Tongji Medical College, Huazhong University of Science and Technology
  • Subei People's Hospital
  • Affiliated Hospital, Guangdong Medical College
  • Henan Provincial People's Hospital
  • Zhengzhou People's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Combination group

Tobramycin inhalation solution alone group

Oral ciprofloxacin alone group

Placebo group

Arm Description

Participants will receive inhaled 300mg of tobramycin solution twice daily for 12 weeks and oral 750mg of ciprofloxacin twice daily for 2 weeks

Participants will receive inhaled 300mg of tobramycin twice daily for 12 weeks and oral ciprofloxacin placebo twice daily for 2 weeks

Participants will receive oral 750mg of ciprofloxacin twice daily for 2 weeks and inhaled saline twice daily for 12 weeks

Participants will receive inhaled saline twice daily for 12 weeks and oral ciprofloxacin placebo twice daily for 2 weeks

Outcomes

Primary Outcome Measures

The proportion of patients successfully eradicating PA in each group by the end of the study, defined as a negative sputum culture of PA at both 24 weeks and 36 weeks.
The proportion of patients with negative PA from sputum samples, either spontaneous or induced, in each group by the end of the study, at both 24 and 36 weeks post-randomization

Secondary Outcome Measures

The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 12 weeks after randomization
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 12 weeks after randomization
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 24 weeks after randomization
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 24 weeks after randomization
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 36 weeks after randomization
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 36 weeks after randomization
Time to the first bronchiectasis exacerbation since randomization
Time to the first bronchiectasis exacerbation since randomization
Frequency of bronchiectasis exacerbation since randomization
Frequency of bronchiectasis exacerbation since randomization
Frequency of bronchiectasis exacerbation since randomization
Frequency of bronchiectasis exacerbation since randomization
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Time to reoccurrence of P. aeruginosa infection since randomization
Time to reoccurrence of P. aeruginosa infection since randomization
Quality-of-Life-Bronchiectasis Respiratory Symptom Scale, that measures health-related quality of life
The Quality-of-Life-Bronchiectasis (QoL-B) questionnaire is a disease-specific survey designed for patients with bronchiectasis. The Respiratory Symptoms scale is a component of the QoL-B questionnaire, with a scale range from 0 to 100. Higher scores on this scale signify a better health status.
St.George Respiratory Questionnaire, that measures health-related quality of life
St.George Respiratory Questionnaire (SGRQ): a validated questionnaire for use in bronchiectasis population. This questionnaire is structured into 3 main components: symptoms, activity and impacts. Scale range is 0-100, where lower scores correspond to the better health status. Each questionnaire response has a unique empirically derived "weight". Each component of the questionnaire is scored separately in three steps: i. The weights for all items with a positive responses are summed. ii. The weights for missed items are deducted from the maximum possible weight for each component. The weights for all missed items are deducted from the maximum possible weight for the Total score. iii. The score is calculated by dividing the summed weights by the adjusted maximum possible weight for that component and expressing the result as a percentage The Total score is calculated in similar way.
Euroqual-5 Dimensions questionnaire
The Euroqual-5 Dimensions questionnaire (EQ-5D) consists of two parts: health state description and evaluation. In the description part, health status is measured across five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents rate their severity level for each dimension using a five-level (EQ-5D-5L) scale. In the evaluation part, respondents assess their overall health status using the visual analogue scale (EQ-VAS), which ranges from 0 to 100, with higher scores indicating a better health status. Health states defined by the EQ-5D-5L descriptive system are converted into index values. This facilitates the calculation of Quality-Adjusted Life Years (QALYs), which are used to inform economic evaluations of healthcare interventions, according to guidelines found at https://euroqol.org.
Changes in forced expiratory volume in 1 second [FEV1] at 12, 24, and 36 weeks compared with baseline
Changes in forced expiratory volume in 1 second [FEV1] at 12, 24, and 36 weeks compared with baseline
Changes in forced vital capacity [FVC] at 12, 24, and 36 weeks compared with baseline
Changes in forced vital capacity [FVC] at 12, 24, and 36 weeks compared with baseline
Changes in forced expiratory flow at 25-75% of forced vital capacity at 12, 24, and 36 weeks compared with baseline
Changes in forced expiratory flow at 25-75% of forced vital capacity at 12, 24, and 36 weeks compared with baseline
The cost of hospitalization
The cost of hospitalization during the whole study period
Other sputum microbiology during the whole study period.
Sputum cultures were conducted at baseline, 2 weeks, 8 weeks, 12 weeks, 24 weeks, and 36 weeks. Other sputum microbiology, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Burkholderia cepacia complex, Stenotrophomonas, Aspergillus, and Candida spp. were documented throughout the entire study period. The number of participants who yielded at least one positive culture for these microorganisms was calculated.
Resistant P. aeruginosa during the whole study period
Sputum cultures were performed at intervals of 2 weeks, 8 weeks, 12 weeks, 24 weeks, and 36 weeks. Drug sensitivity testing was conducted to assess the resistance of the current P. aeruginosa sample to antibiotics such as ciprofloxacin and tobramycin. The number of participants who showed growth of Pseudomonas aeruginosa resistant to ciprofloxacin and/or tobramycin was calculated.
Number of adverse events
Reported by the PI or designee via interview with patients.

Full Information

First Posted
October 10, 2023
Last Updated
October 16, 2023
Sponsor
Shanghai Pulmonary Hospital, Shanghai, China
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1. Study Identification

Unique Protocol Identification Number
NCT06093191
Brief Title
Tobramycin Inhalation Solution for Pseudomonas Aeruginosa Eradication in Bronchiectasis
Acronym
ERASE
Official Title
Efficacy and Safety of tobRamycin Inhalation Solution for Pseudomonas AeruginoSa Eradication in Bronchiectasis (ERASE): Study Protocol for a Multi-center, 2×2 Factorial Randomized, Double-blind, Placebo-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2023 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Pulmonary Hospital, Shanghai, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
People with bronchiectasis are prone to Pseudomonas aeruginosa (PA) infections, which can become chronic and lead to increased death rates and disease severity. Studies from cystic fibrosis suggest that eradication therapy aimed at PA can successfully transition patients to a culture-negative status, providing long-term benefits. Current guidelines for managing bronchiectasis in adults recommend eradicating PA when it is first or newly isolated; however, there is a lack of randomized controlled trials supporting such recommendations. The researchers hypothesize that both oral ciprofloxacin combined with Tobramycin inhalation solution and Tobramycin inhalation solution alone are superior to no eradication (inhaled saline) in terms of the eradication rates of PA, defined as a negative sputum culture of PA at both 24 weeks and 36 weeks.
Detailed Description
The presence of Pseudomonas aeruginosa (PA) in bronchiectasis patients is associated with a greater impairment in lung function, increased systemic and airway inflammation, more frequent exacerbations, decreased quality of life, a higher risk of hospitalization, and increased mortality. Current guidelines recommend eradicating PA when it is first isolated, but there is limited randomized controlled trial evidence to support this. In cystic fibrosis, early infection with PA is clearly linked to worse outcomes, and eradication is associated with clinical benefits, including improved lung function and reduced hospitalization. Small sample observational studies have shown that eradication therapy following initial PA isolation is efficient, with eradication rates of 40%-57% in bronchiectasis. Therefore, a randomized control trial of PA eradication therapy is needed to determine the microbiological and clinical outcomes of this therapy. There is also uncertainty about whether inhaled antibiotics alone are sufficient to eradicate PA in non-cystic fibrosis bronchiectasis, given the less severe nature of the disease compared to cystic fibrosis. It's unclear whether adding another antibiotic, such as oral ciprofloxacin in this study, to inhaled antibiotics at the initial stage is necessary as an enhanced treatment for eradicating PA in bronchiectasis. To address these knowledge gaps, a multicenter, 2×2 factorial randomized, double-blind, placebo-controlled, parallel-group study is designed in bronchiectasis patients with newly or firstly isolated PA. This study aims to investigate the efficacy and safety of tobramycin inhalation solution alone or in combination with oral ciprofloxacin in eradicating PA in bronchiectasis. Patients will be randomly assigned to one of four groups: Placebo group: participants will receive inhaled saline twice daily for 12 weeks and an oral ciprofloxacin placebo twice daily for 2 weeks. Oral ciprofloxacin alone group: participants will receive 750mg of oral ciprofloxacin twice daily for 2 weeks and inhaled saline twice daily for 12 weeks. Tobramycin inhalation solution alone group: participants will receive 300mg of inhaled tobramycin twice daily for 12 weeks and an oral ciprofloxacin placebo twice daily for 2 weeks. Combination group: participants will receive 300mg of inhaled tobramycin solution twice daily for 12 weeks and 750mg of oral ciprofloxacin twice daily for 2 weeks. This study will provide valuable insights into the most effective treatment strategy for eradicating PA in bronchiectasis patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiectasis Adult, Pseudomonas Aeruginosa Infection
Keywords
bronchiectasis,, Pseudomonas Aeruginosa, eradication, inhaled antibiotics, randomized controlled trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomized into one of the four groups. No cross-over of the study group will be made
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Both investigators and participants were blinded to the treatment assignment throughout the study. To maintain this blinding, placebos were used, which were made indistinguishable in appearance from the inhaled tobramycin solution and oral ciprofloxacin. The taste of the inhaled tobramycin solution was not disclosed to the patients, and neither the patients nor most clinicians had prior knowledge of its taste. This blinding approach ensures that both participants and investigators remain unaware of the specific treatment each patient is receiving, thereby reducing potential biases in the study's results
Allocation
Randomized
Enrollment
364 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Combination group
Arm Type
Active Comparator
Arm Description
Participants will receive inhaled 300mg of tobramycin solution twice daily for 12 weeks and oral 750mg of ciprofloxacin twice daily for 2 weeks
Arm Title
Tobramycin inhalation solution alone group
Arm Type
Active Comparator
Arm Description
Participants will receive inhaled 300mg of tobramycin twice daily for 12 weeks and oral ciprofloxacin placebo twice daily for 2 weeks
Arm Title
Oral ciprofloxacin alone group
Arm Type
Active Comparator
Arm Description
Participants will receive oral 750mg of ciprofloxacin twice daily for 2 weeks and inhaled saline twice daily for 12 weeks
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
Participants will receive inhaled saline twice daily for 12 weeks and oral ciprofloxacin placebo twice daily for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Tobramycin Inhalant Product
Other Intervention Name(s)
Inhaled antibiotics
Intervention Description
Tobramycin will be nebulized (300mg twice daily) with an ultrasonic nebulizer. A total of 12 weeks therapy will be scheduled.
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin 750 MG
Other Intervention Name(s)
Oral antibiotics
Intervention Description
Oral ciprofloxacin 750mg twice daily will be prescribed for 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Oral ciprofloxacin placebo
Other Intervention Name(s)
Oral antibiotics
Intervention Description
Oral ciprofloxacin placebo twice daily will be prescribed for 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Natural saline inhalation
Other Intervention Name(s)
Inhaled saline
Intervention Description
Natural saline will be nebulized (5ml twice daily) with an ultrasonic nebulizer. A total of 12 weeks therapy will be scheduled.
Primary Outcome Measure Information:
Title
The proportion of patients successfully eradicating PA in each group by the end of the study, defined as a negative sputum culture of PA at both 24 weeks and 36 weeks.
Description
The proportion of patients with negative PA from sputum samples, either spontaneous or induced, in each group by the end of the study, at both 24 and 36 weeks post-randomization
Time Frame
36 weeks
Secondary Outcome Measure Information:
Title
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 12 weeks after randomization
Description
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 12 weeks after randomization
Time Frame
12 weeks
Title
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 24 weeks after randomization
Description
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 24 weeks after randomization
Time Frame
24 weeks
Title
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 36 weeks after randomization
Description
The proportion of patients in each group who have a negative Pseudomonas aeruginosa (PA) culture 36 weeks after randomization
Time Frame
36 weeks
Title
Time to the first bronchiectasis exacerbation since randomization
Description
Time to the first bronchiectasis exacerbation since randomization
Time Frame
36 weeks
Title
Frequency of bronchiectasis exacerbation since randomization
Description
Frequency of bronchiectasis exacerbation since randomization
Time Frame
36 weeks
Title
Frequency of bronchiectasis exacerbation since randomization
Description
Frequency of bronchiectasis exacerbation since randomization
Time Frame
12 weeks
Title
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Description
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Time Frame
36 weeks
Title
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Description
Frequency of hospitalization due to bronchiectasis exacerbation since randomization
Time Frame
12 weeks
Title
Time to reoccurrence of P. aeruginosa infection since randomization
Description
Time to reoccurrence of P. aeruginosa infection since randomization
Time Frame
36 weeks
Title
Quality-of-Life-Bronchiectasis Respiratory Symptom Scale, that measures health-related quality of life
Description
The Quality-of-Life-Bronchiectasis (QoL-B) questionnaire is a disease-specific survey designed for patients with bronchiectasis. The Respiratory Symptoms scale is a component of the QoL-B questionnaire, with a scale range from 0 to 100. Higher scores on this scale signify a better health status.
Time Frame
Assessed at baseline, 12 weeks, 24 weeks and 36 weeks post-randomization.
Title
St.George Respiratory Questionnaire, that measures health-related quality of life
Description
St.George Respiratory Questionnaire (SGRQ): a validated questionnaire for use in bronchiectasis population. This questionnaire is structured into 3 main components: symptoms, activity and impacts. Scale range is 0-100, where lower scores correspond to the better health status. Each questionnaire response has a unique empirically derived "weight". Each component of the questionnaire is scored separately in three steps: i. The weights for all items with a positive responses are summed. ii. The weights for missed items are deducted from the maximum possible weight for each component. The weights for all missed items are deducted from the maximum possible weight for the Total score. iii. The score is calculated by dividing the summed weights by the adjusted maximum possible weight for that component and expressing the result as a percentage The Total score is calculated in similar way.
Time Frame
Assessed at baseline, 12 weeks, 24 weeks and 36 weeks post-randomization.
Title
Euroqual-5 Dimensions questionnaire
Description
The Euroqual-5 Dimensions questionnaire (EQ-5D) consists of two parts: health state description and evaluation. In the description part, health status is measured across five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents rate their severity level for each dimension using a five-level (EQ-5D-5L) scale. In the evaluation part, respondents assess their overall health status using the visual analogue scale (EQ-VAS), which ranges from 0 to 100, with higher scores indicating a better health status. Health states defined by the EQ-5D-5L descriptive system are converted into index values. This facilitates the calculation of Quality-Adjusted Life Years (QALYs), which are used to inform economic evaluations of healthcare interventions, according to guidelines found at https://euroqol.org.
Time Frame
Assessed at baseline, 12 weeks, 24 weeks and 36 weeks post-randomization.
Title
Changes in forced expiratory volume in 1 second [FEV1] at 12, 24, and 36 weeks compared with baseline
Description
Changes in forced expiratory volume in 1 second [FEV1] at 12, 24, and 36 weeks compared with baseline
Time Frame
Assessed at baseline, 12 weeks, 24 weeks and 36 weeks post-randomization.
Title
Changes in forced vital capacity [FVC] at 12, 24, and 36 weeks compared with baseline
Description
Changes in forced vital capacity [FVC] at 12, 24, and 36 weeks compared with baseline
Time Frame
Assessed at baseline, 12 weeks, 24 weeks and 36 weeks post-randomization.
Title
Changes in forced expiratory flow at 25-75% of forced vital capacity at 12, 24, and 36 weeks compared with baseline
Description
Changes in forced expiratory flow at 25-75% of forced vital capacity at 12, 24, and 36 weeks compared with baseline
Time Frame
Assessed at baseline, 12 weeks, 24 weeks and 36 weeks post-randomization.
Title
The cost of hospitalization
Description
The cost of hospitalization during the whole study period
Time Frame
36 weeks
Title
Other sputum microbiology during the whole study period.
Description
Sputum cultures were conducted at baseline, 2 weeks, 8 weeks, 12 weeks, 24 weeks, and 36 weeks. Other sputum microbiology, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Burkholderia cepacia complex, Stenotrophomonas, Aspergillus, and Candida spp. were documented throughout the entire study period. The number of participants who yielded at least one positive culture for these microorganisms was calculated.
Time Frame
36 weeks
Title
Resistant P. aeruginosa during the whole study period
Description
Sputum cultures were performed at intervals of 2 weeks, 8 weeks, 12 weeks, 24 weeks, and 36 weeks. Drug sensitivity testing was conducted to assess the resistance of the current P. aeruginosa sample to antibiotics such as ciprofloxacin and tobramycin. The number of participants who showed growth of Pseudomonas aeruginosa resistant to ciprofloxacin and/or tobramycin was calculated.
Time Frame
36 weeks
Title
Number of adverse events
Description
Reported by the PI or designee via interview with patients.
Time Frame
36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, aged 18 years and 80 years at screening Signed and dated written informed consent prior to admission to the study in accordance with local legislation. Clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections) and investigator-confirmed diagnosis of bronchiectasis by CT scan During the screening period, patients must have a positive P. aeruginosa culture in their sputum and must meet one of the following criteria: (1) they have never been isolated with P. aeruginosa from sputum or bronchoalveolar lavage fluid (BALF) before; (2) they were isolated with P. aeruginosa from sputum or BALF for the first time within 12 months before screening; (3) they had prior isolation of P. aeruginosa but not within the last 24 months (defined as having negative sputum culture results at least twice before starting antibiotic treatment) During the screening period, patients must remain clinically stable (no significant changes in respiratory symptoms and no upper respiratory tract infection or bronchiectasis exacerbations for 4 weeks) During the screening period, P. aeruginosa is not resistant to Tobramycin and Ciprofloxacin based on the drug sensitivity test of sputum culture in vitro Patient can tolerate nebulized inhalation therapy Exclusion criteria Patients who are allergic to or cannot tolerate the investigational drugs (Tobramycin, Ciprofloxacin) Patients with uncontrolled asthma, physician-diagnosed cystic fibrosis, and Current diagnosis of allergic bronchopulmonary aspergillosis, hypogammaglobulinemia, common variable immunodeficiency, mycobacterial infection (including pulmonary non-tuberculous mycobacterial disease) requiring treatment. Participants with unstable cardiovascular and cerebrovascular diseases, defined as those who have experienced clinically worsening symptoms (such as unstable angina, rapid atrial fibrillation, cerebral hemorrhage, acute cerebral infarction, etc.) or have been hospitalized due to these diseases within 90 days prior to the screening Participants with progressive or uncontrolled systemic diseases, such as those affecting the urinary, hematological, digestive, endocrine, respiratory, circulatory, nervous, or mental systems, are not suitable for this clinical trial. This is particularly the case if these conditions are evaluated by the researcher as being unstable or potentially escalating into severe conditions during the trial. AST and/or ALT >2 ULN at screening period Serum creatinine >ULN at screening period Participants with a history of hearing loss or those who are determined by the researcher to have clinically significant chronic tinnitus Participants with a history of prolonged QT intervals or those whose electrocardiograms show prolonged QT intervals during the screening period Participants who have used drugs that are prohibited according to the plan during the screening period. Women of childbearing potential adhering to contraception requirements. Patients with FEV1% of predicted value<30% Participants who have participated in other clinical trials (defined as those where medication has been administered) within the 4 weeks prior to the screening Participants who have experienced moderate or severe hemoptysis (defined as expectorating 100-500ml of blood in 24 hours for moderate hemoptysis; and expectorating more than 500ml in 24 hours, or a single instance of expectorating more than 100ml of blood for severe hemoptysis) due to bronchiectasis within the past 6 months. Participants who are deemed unsuitable for inclusion in the study due to other reasons, as determined by the researcher.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jin-Fu Xu, PhD
Phone
+8613321922898
Email
jfxucn@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin-Fu Xu, PhD
Organizational Affiliation
Shanghai Pulmonary Hospital, Shanghai, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie-ming Qu, MD
First Name & Middle Initial & Last Name & Degree
Jie-ming Qu, MD
Facility Name
The Shanghai Fifth People's Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200245
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhi-jun Jie, MD
First Name & Middle Initial & Last Name & Degree
Zhi-jun Jie, MD
Facility Name
Shanghai pulmonary hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200433
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin-Fu Xu, MD
Phone
+8613321922898
Email
jfxucn@163.com
Facility Name
The First People's Hospital of Anning City Affiliated to Kunming University of Science and Technology
City
Anning
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian He, MD
Facility Name
Beijing Chao-Yang Hospital, Capital Medical University
City
Beijing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhao-hui Tong, MD
Facility Name
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
City
Beijing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xin-lun Tian, MD
Facility Name
Peking University Third Hospital
City
Beijing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong-chang Sun, MD
Facility Name
The First Affiliated Hospital of Jilin University
City
Changchun
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dan Li, MD
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hong Luo, MD
Facility Name
Xiangya Hospital, Central South University
City
Changsha
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuan-yuan Li, MD
Facility Name
West China Hospital of Sichuan University
City
Chengdu
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hong Fan, MD
Facility Name
The Second Affiliated Hospital of Chongqing Medical University
City
Chongqing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dao-xin Wang, MD
Facility Name
The Third Affiliated Hospital of Chongqing Medical University
City
Chongqing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chang-zheng Wang, MD
Facility Name
The Second Affiliated Hospital of Dalian Medical University
City
Dalian
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qi Wang, MD
Facility Name
Fujian Provincial Hospital
City
Fuzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bao-song Xie, MD
Facility Name
The First Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei-jie Guan, MD
Facility Name
The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
City
Guangzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shao-feng Zhan, MD
Facility Name
The First Affiliated Hospital of Jinan University
City
Guangzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sheng-ming Liu, MD
Facility Name
Guizhou Provincial People's Hospital
City
Guiyang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lin Liu, MD
Facility Name
The Second Affiliated Hospital of Zhengjiang University
City
Hangzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen Li, MD
Facility Name
Anhui Chest Hospital
City
Hefei
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hua Niu, MD
Facility Name
The First Affiliated Hospital of Anhui Medical University
City
Hefei
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiao-yun Fan, MD
Facility Name
Huzhou Central Hospital
City
Huzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bin Wang, MD
Facility Name
The First Hospital of Jiaxing City
City
Jiaxing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiao-dong Lv, MD
Facility Name
The Second Hospital of Jiaxing City
City
Jiaxing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei-qiang Mo, MD
Facility Name
Qilu Hospital of Shandong University
City
Jinan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Li, MD
Facility Name
The First Affiliated Hospital of Shandong First Medical University
City
Jinan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liang Dong, MD
Facility Name
The First Affiliated Hospital of Wenzhou Medical University
City
Jinan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu-ping Li, MD
Facility Name
The First Affiliated Hospital of Nanchang University
City
Nanchang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Zhang, MD
First Name & Middle Initial & Last Name & Degree
Tian-xin Xiang, MD
Facility Name
Affiliated Hospital of Yifu, Nanjing Medical University
City
Nanjing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gan-zhu Feng, MD
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanning
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing-min Deng, MD
Facility Name
Affiliated Hospital, Nantong University
City
Nantong
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Feng, MD
Facility Name
The Sixth People's Hospital of Nantong City
City
Nantong
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hong-yan Gu, MD
Facility Name
Fenghua District People's Hospital of Ningbo City
City
Ningbo
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chao Yuan, MD
Facility Name
Ningbo Medical Center Lihuili Hospital
City
Ningbo
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing-bo Jiang, MD
Facility Name
The First Affiliated Hospital of Ningbo University
City
Ningbo
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chao Cao, MD
Facility Name
Qingdao Municipal Hospital
City
Qingdao
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xue-dong Liu, MD
Facility Name
Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Li, MD
Facility Name
Shanghai Eighth People's Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
De-jie Chu, MD
Facility Name
Shanghai General Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Zhang, MD
Facility Name
Shanghai Putuo District People's Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Feng-ying Zhang, MD
Facility Name
Shanghai Shidong Hospital of Yangpu District
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jia Qin, MD
Facility Name
Shanghai Sixth People's Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tao Ren, MD
Facility Name
Shanghai Songjiang District Central Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fan Li, MD
Facility Name
Shanghai Yangpu District Central Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cui-xia Zheng, MD
Facility Name
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shan-ping Jiang, MD
Facility Name
Zhongshan Hospital, Fudan University
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuan-lin Song, MD
Facility Name
Shangrao People's Hospital
City
Shangrao
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qing-wei Meng, MD
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Chen, MD
Facility Name
The First Affiliated Hospital of China Medical University
City
Shenyang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Wang, MD
Facility Name
Shenzhen Institute of Respiratory Diseases
City
Shenzhen
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ling-wei Wang, MD
Facility Name
The Eighth Affiliated Hospital of Sun Yat-Sen University
City
Shenzhen
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian-quan Zhang, MD
Facility Name
Suzhou Science and Technology Town Hospital
City
Suzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chao Yang, MD
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian-an Huang, MD
Facility Name
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Xie, MD
Facility Name
Union Hospital,Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Jin, MD
Facility Name
Subei People's Hospital
City
Yangzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ling-feng Min, MD
Facility Name
Affiliated Hospital, Guangdong Medical College
City
Zhanjiang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bin Wu, MD
Facility Name
Henan Provincial People's Hospital
City
Zhengzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiao-ju Zhang, MD
Facility Name
Zhengzhou People's Hospital
City
Zhengzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin-guang Jia, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28889110
Citation
Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, Murris M, Canton R, Torres A, Dimakou K, De Soyza A, Hill AT, Haworth CS, Vendrell M, Ringshausen FC, Subotic D, Wilson R, Vilaro J, Stallberg B, Welte T, Rohde G, Blasi F, Elborn S, Almagro M, Timothy A, Ruddy T, Tonia T, Rigau D, Chalmers JD. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017 Sep 9;50(3):1700629. doi: 10.1183/13993003.00629-2017. Print 2017 Sep.
Results Reference
background
PubMed Identifier
30545985
Citation
Hill AT, Sullivan AL, Chalmers JD, De Soyza A, Elborn SJ, Floto AR, Grillo L, Gruffydd-Jones K, Harvey A, Haworth CS, Hiscocks E, Hurst JR, Johnson C, Kelleher PW, Bedi P, Payne K, Saleh H, Screaton NJ, Smith M, Tunney M, Whitters D, Wilson R, Loebinger MR. British Thoracic Society Guideline for bronchiectasis in adults. Thorax. 2019 Jan;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463. No abstract available.
Results Reference
background
PubMed Identifier
27288031
Citation
Aliberti S, Masefield S, Polverino E, De Soyza A, Loebinger MR, Menendez R, Ringshausen FC, Vendrell M, Powell P, Chalmers JD; EMBARC Study Group. Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration. Eur Respir J. 2016 Sep;48(3):632-47. doi: 10.1183/13993003.01888-2015. Epub 2016 Jun 10.
Results Reference
background
PubMed Identifier
22204744
Citation
White L, Mirrani G, Grover M, Rollason J, Malin A, Suntharalingam J. Outcomes of Pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis. Respir Med. 2012 Mar;106(3):356-60. doi: 10.1016/j.rmed.2011.11.018. Epub 2011 Dec 26.
Results Reference
background
PubMed Identifier
28404646
Citation
Vallieres E, Tumelty K, Tunney MM, Hannah R, Hewitt O, Elborn JS, Downey DG. Efficacy of Pseudomonas aeruginosa eradication regimens in bronchiectasis. Eur Respir J. 2017 Apr 12;49(4):1600851. doi: 10.1183/13993003.00851-2016. Print 2017 Apr. No abstract available.
Results Reference
background
PubMed Identifier
31480862
Citation
Blanco-Aparicio M, Saleta Canosa JL, Valino Lopez P, Martin Egana MT, Vidal Garcia I, Montero Martinez C. Eradication of Pseudomonas aeruginosa with inhaled colistin in adults with non-cystic fibrosis bronchiectasis. Chron Respir Dis. 2019 Jan-Dec;16:1479973119872513. doi: 10.1177/1479973119872513.
Results Reference
background
PubMed Identifier
26340658
Citation
Orriols R, Hernando R, Ferrer A, Terradas S, Montoro B. Eradication Therapy against Pseudomonas aeruginosa in Non-Cystic Fibrosis Bronchiectasis. Respiration. 2015;90(4):299-305. doi: 10.1159/000438490. Epub 2015 Sep 5.
Results Reference
background
PubMed Identifier
30635292
Citation
Pieters A, Bakker M, Hoek RAS, Altenburg J, van Westreenen M, Aerts JGJV, van der Eerden MM. The clinical impact of Pseudomonas aeruginosa eradication in bronchiectasis in a Dutch referral centre. Eur Respir J. 2019 Apr 11;53(4):1802081. doi: 10.1183/13993003.02081-2018. Print 2019 Apr. No abstract available.
Results Reference
background

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Tobramycin Inhalation Solution for Pseudomonas Aeruginosa Eradication in Bronchiectasis

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