Efficacy & Tolerability of Tobramycin Podhaler in Bronchiectasis Patients With Chronic Pseudomonas Aeruginosa Infection (TOBI)

The use of inhaled medications for the treatment of pulmonary diseases allows for the delivery of a high concentration of a drug at the site of disease with reduced systemic absorption and risk of systemic adverse effects. Inhaled Tobramycin has been successfully used in the maintenance treatment of CF patients with chronic colonization with PA (Pseudomonas aeruginosa). In the CF population TOBI has been proven to improve lung functions, decrease the density of the PA in the sputum, decrease hospitalizations, and reduce the risk of mortality.

Non CF Bronchiectasis share many features in common with CF, including frequent colonization with PA that leads to deterioration in lung function and increased morbidity. A recent Cochrane review concluded that there is a small benefit for the use of prolonged antibiotics in the treatment of bronchiectasis, however further randomized controlled trials with adequate power and standardized end points are required.

There have been reports in the literature describing the efficacy of inhaled tobramycin the treatment of patients with non CF bronchiectasis with eradication of PA, and significant improvement in respiratory symptoms. There were however patients who discontinued treatment due to adverse events most commonly cough wheezing and dyspnea. (Scheinberg and Shore, Chest 2005).

TOBI Podhaler is a dry powder inhaler that was recently launched, and is much easier and faster to use compared to nebulised Tobramycin. To the best of our knowledge Tobramycin dry powder formulation has not yet been trialed in patients with non CF bronchiectasis.

The purpose of this trial is to assess the efficacy and tolerability of TOBI Podhaler in patients with non CF bronchiectasis, and to gather more data on the benefit of continuous antibiotic therapy in patients with non CF bronchectais.

Study Overview

• Status: Unknown
• Conditions: Bronchiectasis With Chronic Infection With Pseudomonas Aeruginosa
• Intervention / Treatment: Drug: Tobramycin

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
    • Pulmonary Institute, Rabin Medical Center, Beilinson Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with bronchiectasis confirmed by CT
2. Chronic PA colonization with 2 documented sputum cultures positive for PA in the last 24 months.
3. Age >=18

Exclusion Criteria:

1. Patients diagnosed with CF
2. Patients who do not tolerate Tobramycin
3. Pregnant or breastfeeding
4. Patients treated in the last 8 weeks with antibiotic therapy either inhaled or systemic (excluding Azenil PO x 3/week which is allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TOBI / Placebo; TOBI / Placebo.	Drug: Tobramycin
Active Comparator: Placebo / TOBI	Drug: Tobramycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of exacerbations as measured by number of systemic courses of antibiotics either PO or IV	Exacerbation count at 24 weeks, 48 weeks and 52 weeks	52 weeks total

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life and Symptoms Score as measured by SGRQ(Saint George's Respiratory Questionnaire) and CASA-Q-CD (Cough and Sputum Assessment Questionnaire) cough and sputum domains	Control Period Patients will visit the site 3 times every 12 weeks, TOBI Period Patients will visit the clinic at least 4 times a year during this 24 week period, when enrolled to the study during the 48 weeks period of the study	52 weeks
Pulmonary function tests (FEV1)	Control Period Patients will visit site 3 times every 12 weeks, TOBI Period Patients will visit the clinic at least 4 times a year during this 24 week period, when enrolled to the study during the 48 weeks period of the study	52 weeks
Sputum microbiology: Change in Pseudomona Aeruginosa density in sputum	Samples will be taken at every visit and changes will be analyzed at the end of the study, when enrolled to the study during the 48 weeks period of the study PENDING finding a lab that can perform this test (CFU quantitation).	52 weeks
Safety and Tolerability of TOBI podhaler	Adverse Events and Serious Adverse Events will be monitored continuously in the study and analyzed at the end of study, when enrolled to the study during the 48 weeks period of the study, plus 4 weeks wash-out.	52 weeks

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Study Chair: Mordechai R Kramer, MD, Rabin Medical Center

Publications and helpful links

General Publications

• 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.
• Konstan MW, Flume PA, Kappler M, Chiron R, Higgins M, Brockhaus F, Zhang J, Angyalosi G, He E, Geller DE. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cyst Fibros. 2011 Jan;10(1):54-61. doi: 10.1016/j.jcf.2010.10.003. Epub 2010 Nov 12.
• Cochrane review: Prolonged antibiotics for purulent bronchiectasis in children and adults (Review), Evans DJ, Bara A, Greenstone M. The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. 13 January 2011.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): April 1, 2016
• Study Completion (Anticipated): May 1, 2016

Study Registration Dates

• First Submitted: March 6, 2014
• First Submitted That Met QC Criteria: March 30, 2014
• First Posted (Estimate): April 2, 2014

Study Record Updates

• Last Update Posted (Estimate): April 2, 2014
• Last Update Submitted That Met QC Criteria: March 30, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: bronchiectasis; chronic infection; Tobramycin Podhaler; Pseudomonas Aeruginosa
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Bronchial Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Bronchiectasis; Infections; Communicable Diseases; Pseudomonas Infections; Anti-Infective Agents; Anti-Bacterial Agents; Tobramycin
• Other Study ID Numbers: RMCBH147441