Tobramycin in Bronchiectasis Colonized With Pseudmonas Aeruginosa

NCT ID: NCT03715322

Last Updated: 2019-08-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-26

Study Completion Date

2021-06-30

Brief Summary

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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

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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.

Conditions

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Bronchiectasis Adult Pseudomonas Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients will be randomized into the treatment group and control group. No cross-over of the study group will be made.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Both the investigators and the participants will be masked to the study allocation. The randonmization codes will be generated by a blinded medical statistician with the use of computerized program. Randomization will be achieved based on the permuted block design.

Study Groups

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tobramycin inhalation

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

Group Type ACTIVE_COMPARATOR

Tobramycin Inhalant Product

Intervention Type DRUG

Tobramycin will be nebulized (300mg twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.

usual care

Intervention Type OTHER

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

natural saline inhalation

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

Group Type PLACEBO_COMPARATOR

usual care

Intervention Type OTHER

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

Natural saline inhalation

Intervention Type DRUG

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.

usual care

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

Group Type OTHER

Tobramycin Inhalant Product

Intervention Type DRUG

Tobramycin will be nebulized (300mg twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.

Natural saline inhalation

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

usual care

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

Intervention Type OTHER

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Guangzhou Institute of Respiratory Disease

OTHER

Sponsor Role lead

Responsible Party

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Weijie Guan

Associated professor; principal investigator (respiratory medicine)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nan-shan Zhong, MD

Role: STUDY_CHAIR

The First Affiliated Hospital of Guangzhou Medical University

Wei-jie Guan, PhD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Guangzhou Medical University

Locations

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The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Nan-shan Zhong, MD

Role: CONTACT

13609003622

Wei-jie Guan, PhD

Role: CONTACT

+86-13826042052

Facility Contacts

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Nan-shan Zhong, MD

Role: primary

+86-13609003622

References

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Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119.

Reference Type BACKGROUND
PMID: 20627931 (View on PubMed)

Pasteur MC, Helliwell SM, Houghton SJ, Webb SC, Foweraker JE, Coulden RA, Flower CD, Bilton D, Keogan MT. An investigation into causative factors in patients with bronchiectasis. Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1277-84. doi: 10.1164/ajrccm.162.4.9906120.

Reference Type BACKGROUND
PMID: 11029331 (View on PubMed)

Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Aetiology of bronchiectasis in Guangzhou, southern China. Respirology. 2015 Jul;20(5):739-48. doi: 10.1111/resp.12528. Epub 2015 Mar 26.

Reference Type BACKGROUND
PMID: 25819403 (View on PubMed)

Angrill J, Agusti C, De Celis R, Filella X, Rano A, Elena M, De La Bellacasa JP, Xaubet A, Torres A. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1628-32. doi: 10.1164/ajrccm.164.9.2105083.

Reference Type BACKGROUND
PMID: 11719301 (View on PubMed)

Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012 Oct 1;186(7):657-65. doi: 10.1164/rccm.201203-0487OC. Epub 2012 Jun 28.

Reference Type BACKGROUND
PMID: 22744718 (View on PubMed)

Davies G, Wells AU, Doffman S, Watanabe S, Wilson R. The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis. Eur Respir J. 2006 Nov;28(5):974-9. doi: 10.1183/09031936.06.00074605. Epub 2006 Aug 9.

Reference Type BACKGROUND
PMID: 16899482 (View on PubMed)

Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Li ZM, Zheng JP, Chen RC, Zhong NS. Effect of airway Pseudomonas aeruginosa isolation and infection on steady-state bronchiectasis in Guangzhou, China. J Thorac Dis. 2015 Apr;7(4):625-36. doi: 10.3978/j.issn.2072-1439.2015.04.04.

Reference Type BACKGROUND
PMID: 25973228 (View on PubMed)

Wilson R, Aksamit T, Aliberti S, De Soyza A, Elborn JS, Goeminne P, Hill AT, Menendez R, Polverino E. Challenges in managing Pseudomonas aeruginosa in non-cystic fibrosis bronchiectasis. Respir Med. 2016 Aug;117:179-89. doi: 10.1016/j.rmed.2016.06.007. Epub 2016 Jun 7.

Reference Type BACKGROUND
PMID: 27492530 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26340658 (View on PubMed)

Hoppentocht M, Akkerman OW, Hagedoorn P, Alffenaar JW, van der Werf TS, Kerstjens HA, Frijlink HW, de Boer AH. Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin Free Base in Non-Cystic Fibrosis Bronchiectasis Patients. PLoS One. 2016 Mar 9;11(3):e0149768. doi: 10.1371/journal.pone.0149768. eCollection 2016.

Reference Type BACKGROUND
PMID: 26959239 (View on PubMed)

Bilton D, Henig N, Morrissey B, Gotfried M. Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis. Chest. 2006 Nov;130(5):1503-10. doi: 10.1378/chest.130.5.1503.

Reference Type BACKGROUND
PMID: 17099030 (View on PubMed)

Scheinberg P, Shore E. A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis. Chest. 2005 Apr;127(4):1420-6. doi: 10.1378/chest.127.4.1420.

Reference Type BACKGROUND
PMID: 15821224 (View on PubMed)

Drobnic ME, Sune P, Montoro JB, Ferrer A, Orriols R. Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother. 2005 Jan;39(1):39-44. doi: 10.1345/aph.1E099. Epub 2004 Nov 23.

Reference Type BACKGROUND
PMID: 15562142 (View on PubMed)

Couch LA. Treatment With tobramycin solution for inhalation in bronchiectasis patients with Pseudomonas aeruginosa. Chest. 2001 Sep;120(3 Suppl):114S-117S. doi: 10.1378/chest.120.3_suppl.114s.

Reference Type BACKGROUND
PMID: 11555565 (View on PubMed)

Orriols R, Roig J, Ferrer J, Sampol G, Rosell A, Ferrer A, Vallano A. Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa. Respir Med. 1999 Jul;93(7):476-80. doi: 10.1016/s0954-6111(99)90090-2.

Reference Type BACKGROUND
PMID: 10464834 (View on PubMed)

Barker AF, Couch L, Fiel SB, Gotfried MH, Ilowite J, Meyer KC, O'Donnell A, Sahn SA, Smith LJ, Stewart JO, Abuan T, Tully H, Van Dalfsen J, Wells CD, Quan J. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):481-5. doi: 10.1164/ajrccm.162.2.9910086.

Reference Type BACKGROUND
PMID: 10934074 (View on PubMed)

Guan WJ, Xu JF, Luo H, Xu XX, Song YL, Ma WL, Liang ZA, Liu XD, Zhang GJ, Zhang XJ, Li RK, Zhu SY, Zhang YJ, Cai XJ, Wei LP, Tian DB, Zhao H, Chen PY, Qu JM, Zhong NS; TORNASOL Study Group. A Double-Blind Randomized Placebo-Controlled Phase 3 Trial of Tobramycin Inhalation Solution in Adults With Bronchiectasis With Pseudomonas aeruginosa Infection. Chest. 2023 Jan;163(1):64-76. doi: 10.1016/j.chest.2022.07.007. Epub 2022 Jul 19.

Reference Type DERIVED
PMID: 35863486 (View on PubMed)

Other Identifiers

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GIRH-2018-TOBRA

Identifier Type: -

Identifier Source: org_study_id

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