Tobramycin Inhalation Solution for Pseudomonas Aeruginosa Eradication in Bronchiectasis
Efficacy and Safety of tobRamycin Inhalation Solution for Pseudomonas AeruginoSa Eradication in Bronchiectasis (ERASE): a Multi-center, 2×2 Factorial Randomized, Double-blind, Placebo-controlled Trial
Shanghai Pulmonary Hospital, Shanghai, China
364 participants
Sep 25, 2023
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria7
- 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 Criteria14
- 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.
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Interventions
Tobramycin will be nebulized (300mg twice daily) with an ultrasonic nebulizer. A total of 12 weeks therapy will be scheduled.
Oral ciprofloxacin 750mg twice daily will be prescribed for 2 weeks.
Oral ciprofloxacin placebo twice daily will be prescribed for 2 weeks.
Natural saline will be nebulized (5ml twice daily) with an ultrasonic nebulizer. A total of 12 weeks therapy will be scheduled.
Locations(63)
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NCT06093191