Tobramycin in Bronchiectasis Colonized With Pseudmonas Aeruginosa

Brief Title

Tobramycin in Bronchiectasis Colonized With Pseudmonas Aeruginosa

Official Title

Efficacy and Safety of Inhaled Tobramycin on Bronchiectasis Colonized With Pseudomonas Aeruginosa: A Randomized, Double-blind, Parallel-group Multicenter Trial

Brief Summary

      This is a phase 3 study. Patients will be enrolled from 14 medical centers in mainland China.
      Eligible patients will be randomly allocated to treatment group (tobramycin nebulization,
      300mg bid) and control group (natural saline nebulization, 5ml bid). A total of two 28-day
      on-and-off cycles will be scheduled. Both tobramycin solution and natural saline and the
      nebulizer will be solely provided by the sponsor.
    

Detailed Description

      This is a phase 3 study. All bronchiectasis patients will be enrolled from 14 medical centers
      located in different geographic regions of mainland China. After a three-week screening
      period, On the basis of usual care [ambroxool (30mg thrice daily) or N-acetylcysteine (0.2g
      thrice daily) and chest physiotherapy (5 min, once daily)], eligible patients will be
      randomly allocated to treatment group (tobramycin nebulization, 300mg bid, delivered via an
      ultrasonic nebulizer) and control group (natural saline nebulization, 5ml bid, delivered via
      an ultrasonic nebulizer). A total of two 28-day on-and-off cycles will be scheduled. At the
      end of each on-and-off cycle, sputum culture and other clinical assessments will be
      performed.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Changes in sputum load of Pseudomonas aeruginosa at day 29 compared with baseline

Secondary Outcome

 The time to the first bronchiectasis exacerbation since randomization

Condition

Bronchiectasis Adult

Intervention

Tobramycin Inhalant Product

Study Arms / Comparison Groups

 tobramycin inhalation

Description:  300mg tobramycin dissolved in 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

350

Start Date

October 26, 2018

Completion Date

June 2021

Primary Completion Date

April 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Aged 18 to 75 years, had a history of chronic cough and sputum production, had
             physician-diagnosed bronchiectasis based on high-resolution chest computed tomography
             (effective within 12 months)

          -  Remaining clinically stable (no significant changes in respiratory symptoms and free
             from upper respiratory tract infection or bronchiectasis exacerbations for 4 weeks)

          -  Sputum culture positive to Pseudomonas aeruginosa at screening

          -  Forced expiratory volume in one second > 30% predicted and < 80% predicted

          -  Could tolerate to nebulization

          -  At least one bronchiectasis exacerbation within the past two years

          -  Can correctly nebulize the study medications and fill in the diary cards following
             instruction of the investigators

        Exclusion Criteria:

          -  Had a knwon history of allergy to tobramycin

          -  Had concomitant asthma, allergic bronchopulmonary aspergillosis, active tuberculosis,
             or active infection with non-tuyberculous mycobacteria that warranted regular
             anti-mycobacterial treatment

          -  Had moderate or major haemoptysis within 6 months

          -  Had concomitant severe cardiovascular diseases or haematopoietic diseases (congestive
             heart failure, clinically significant coronary heart disease, myocardial infarction or
             stroke, clinically arrythmia, known anurysm of the aorta, uncontroll hypertension
             (systolic blood pressure > 160mmHg or diastolic pressure >100mmHg at two consecutive
             time points)

          -  Concomitant severe psychiatric disorders

          -  Uncontrolled diabetes mellitus or fasting blood glucose >10mmol/L

          -  Active peptic or duodenal ulcer

          -  Moderate-to-severe gastroesophageal reflux diseases

          -  Malignancy

          -  Severe myasthenia gravis or Parkinson's disease

          -  Major abnormality of hepatic or renal function [ALT or AST >2-fold of the normal upper
             limit, creatinine > 1.5-fold- greater than the normal upper limit (excluding ALT >
             1.5-fold greater than normal upper limit in patients with chronic stable hepatitis)];
             concomitant infection with HBV and HCV;

          -  Hearing loss or clinically significant tinittus

          -  Use of inhaled or systemic antibiotics within 4 weeks prior to enrollment

          -  Needing oral or intravenous corticosteroids, or needing systemic corticosteroids
             within 30 days prior to enrollment

          -  Needing oral or intravenous anti-cholinergic medications, or needing systemic
             anti-cholinergic medications within 30 days prior to enrollment

          -  Needing long-term non-invasive mechanical ventilation or oxygen therapy (> 10 hrs
             daily) due to chronic respiratory failure

          -  Pregnancy or lactation

          -  Failure to understand or cooperate with the trial procedures

          -  Participation in other clinical trials within 3 months
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Nan-shan Zhong, MD, 13609003622, [email protected]

Location Countries

China

Location Countries

China

NCT ID

NCT03715322

Organization ID

GIRH-2018-TOBRA

Responsible Party

Principal Investigator

Study Sponsor

Guangzhou Institute of Respiratory Disease

Study Sponsor

Nan-shan Zhong, MD, Study Chair, The First Affiliated Hospital of Guangzhou Medical University

Verification Date

July 2019