Tobramycin in Bronchiectasis Colonized With Pseudmonas Aeruginosa (TORNASOL)

July 31, 2019 updated by: Weijie Guan, Guangzhou Institute of Respiratory Disease

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

350

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510120
        • Recruiting
        • The First Affiliated Hospital of Guangzhou Medical University
        • Contact:
        • Principal Investigator:
          • Wei-jie Guan, PhD
        • Principal Investigator:
          • Guo-jun Zhang, MD
        • Sub-Investigator:
          • Yong-hua Gao, PhD
        • Principal Investigator:
          • Jie-ming Qu, MD
        • Principal Investigator:
          • Jin-fu Xu, MD
        • Principal Investigator:
          • Yuan-lin Song, MD
        • Principal Investigator:
          • Jian-ping Zhao, MD
        • Principal Investigator:
          • Xiao-nan Tao, MD
        • Principal Investigator:
          • Zong-an Liang, MD
        • Principal Investigator:
          • Ping Chen, MD
        • Principal Investigator:
          • Qi-chang Lin, MD
        • Principal Investigator:
          • Yi-jiang Huang, MD
        • Principal Investigator:
          • Xue-dong Liu, MD
        • Principal Investigator:
          • Xing-xiang Xu, MD
        • Principal Investigator:
          • Wei Zhang, MD
        • Principal Investigator:
          • Chang-jun Du, MD
        • Principal Investigator:
          • Xing-lin Gao, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: tobramycin inhalation
300mg tobramycin dissolved in 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.
Drug: Tobramycin Inhalant Product
Tobramycin will be nebulized (300mg twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.
Other: usual care
ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily)
Placebo Comparator: natural saline inhalation
5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.
Other: usual care
ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily)
Drug: Natural saline inhalation
Natural saline will be nebulized (5ml twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.
Other: usual care
ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily)
Drug: Tobramycin Inhalant Product
Tobramycin will be nebulized (300mg twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.
Drug: Natural saline inhalation
Natural saline will be nebulized (5ml twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in sputum load of Pseudomonas aeruginosa at day 29 compared with baseline
Time Frame: 29 days
Changes in sputum load of Pseudomonas aeruginosa at day 29 compared with baseline
29 days
Changes in Quality of Life in Bronchiectasis-Respiratory Symptom Score at day 29 compared with baseline
Time Frame: 29 days
Changes in QoL-B-RSS at day 29 compared with baseline. The respiratory symptom domain contains 9 items describing patient's self assessment of her/his respiratory symptoms that affect the daily life. The total score for this domain is 100, with higher scores indicating better quality of life. No summation was made for the total score.
29 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The time to the first bronchiectasis exacerbation since randomization
Time Frame: 4 months
The time to the first bronchiectasis exacerbation since randomization
4 months
The frequency of bronchiectasis exacerbation since randomization
Time Frame: 4 months
The frequency of bronchiectasis exacerbation since randomization
4 months
The rate of isolation of Pseudomonas aeruginosa at day 85
Time Frame: 85 days
The rate of isolation of Pseudomonas aeruginosa at day 85
85 days
Changes in the load of Pseudomonas aeruginosa at day 85 compared with baseline
Time Frame: 85 days
Changes in the load of Pseudomonas aeruginosa at day 85 compared with baseline
85 days
Changes in FEV1 pred% at days 29, 57 and 85 compared with baseline
Time Frame: 85 days
Changes in the predicted % of forced expiratory volume in one second at days 29, 57 and 85 compared with baseline
85 days
Changes in 24-hour sputum volume at days 29, 57 and 85 compared with baseline
Time Frame: 85 days
Changes in 24-hour sputum volume at days 29, 57 and 85 compared with baseline
85 days
Changes in sputum purulence at days 29, 57 and 85 compared with baseline
Time Frame: 85 days
Changes in sputum purulence at days 29, 57 and 85 compared with baseline
85 days
Changes in Quality of Life in Bronchiectasis-Respiratory Symptom Score at day 85 compared with baseline
Time Frame: 85 days
Changes in QoL-B-RSS at day 85 compared with baseline. The respiratory symptom domain contains 9 items describing patient's self assessment of her/his respiratory symptoms that affect the daily life. The total score for this domain is 100, with higher scores indicating better quality of life. No summation was made for the total score.
85 days
Changes in Bronchiectasis Health Questionnaire Sore at day 29 and 85 compared with baseline
Time Frame: 85 days
Changes in BHQ Sore at day 29 and 85 compared with baseline. Theb BHQ contains 10 items, with higher scores indicating better quality of life. The total score was calculated as the weighted summation of the scores for the 10 individual items.
85 days
Peak and trough concentration of tobramycin at day 1 and 28 post-treatment
Time Frame: 29 days
Peak and trough concentration of tobramycin at day 1 and 28 post-treatment
29 days
Changes in overall visual analogue scale at days 29 and 85 compared with baseline
Time Frame: 85 days
Changes in overall VAS at days 29 and 85 compared with baseline. The VAS ranged from 0 to 10, with higher scores indicating poorer status. No summation of the score was made.
85 days
Changes in the minimal inhibitory concentration of Pseudomonas aeruginosa at days 29 and 85 compared with baseline
Time Frame: 85 days
Changes in the MIC of Pseudomonas aeruginosa at days 29 and 85 compared with baseline (assessed with dilution methods for the sputum culture samples)
85 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangzhou Institute of Respiratory Disease

Investigators

  • Study Chair: Nan-shan Zhong, MD, The First Affiliated Hospital of Guangzhou Medical University
  • Principal Investigator: Wei-jie Guan, PhD, The First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2018

Primary Completion (Anticipated)

April 1, 2021

Study Completion (Anticipated)

June 1, 2021

Study Registration Dates

First Submitted

October 19, 2018

First Submitted That Met QC Criteria

October 19, 2018

First Posted (Actual)

October 23, 2018

Study Record Updates

Last Update Posted (Actual)

August 2, 2019

Last Update Submitted That Met QC Criteria

July 31, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIRH-2018-TOBRA

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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