Tobramycin in Bronchiectasis Colonized With Pseudmonas Aeruginosa (TORNASOL)

Guangzhou Institute of Respiratory Disease

Status and phase: Unknown; Phase 3

Conditions: Pseudomonas Infections; Bronchiectasis Adult

Treatments: Drug: Tobramycin Inhalant Product; Other: usual care; Drug: Natural saline inhalation

Study type: Interventional

Funder types: Other

Identifiers

NCT03715322

GIRH-2018-TOBRA

Details and patient eligibility

About

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.

Full 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.

Enrollment: 350 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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350 participants in 3 patient groups, including a placebo group

tobramycin inhalation

Active Comparator group

Description:

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

Treatment:

Other: usual care

Drug: Tobramycin Inhalant Product

natural saline inhalation

Placebo Comparator group

Description:

5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.

Treatment:

Other: usual care

Drug: Natural saline inhalation

usual care

Other group

Description:

ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily)

Treatment:

Drug: Natural saline inhalation

Drug: Tobramycin Inhalant Product