Evaluation of Lung Clearance Index in Cystic Fibrosis (CF) Patients, Infected With P.Aeruginosa

Study Overview
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Brief Summary
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The purpose of the study was to evaluate lung clearance index (LCI) by a standardized procedure in a well characterized study setting and to assess feasibility of LCI as a more sensitive method than forced expiratory volume at 1 second (FEV1) to measure effectiveness of antibiotic therapy in patients with CF aged 6 years and older with mild to moderate lung disease.

Detailed Description
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This study was terminated prematurely. The reason for trial termination was challenge with enrollment and patient recruitment. A significant decrease in the eligible patient population had been identified as main driver.

Official Title
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An 8 Week Open-label Interventional Multicenter Study to Evaluate the Lung Clearance Index as Endpoint for Clinical Trials in Cystic Fibrosis Patients ≥ 6 Years of Age, Chronically Infected With Pseudomonas Aeruginosa

Conditions
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Chronic Lung Infection With Pseudomonas Aeruginosa in Cystic Fibrosis

Intervention / Treatment
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* Drug: TIS or TIP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CF Patients with elevated LCI of ≥ 7.5 at screening Patients with FEV1 of ≥ 50% predicted at screening Use of inhaled Tobramycin in a 28 days on / off regimen in the past 3 months before screening chronic lung Infection with Pseudomonas aeruginosa Exclusion Criteria: Patients who are regularly receiving more than one class of inhaled anti-pseudomonal antibiotic Patients who have used oral or intravenous anti-pseudomonal antibiotics within 28 days prior to on-phase of study drug Pregnant or nursing (lactating) women Change in dose, formulation or strength of the study drug in the past treatment cycle before screening History of hearing loss or chronic tinnitus Infection with Burkholderia cenocepacia complex Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tobramycin ALL<br>300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off | Drug: TIS or TIP<br>* 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Lung Clearance Index (LCI) After 4 Weeks Following Onset of Study | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | Baseline, week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of Forced Expiratory Volume at 1 Second (FEV1) After 4 Weeks Following Onset of Study | Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry | Baseline, week 4 | 
| Change From Baseline of Colony-forming Units (CFU) After 4 Weeks Following Onset of Study | Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum. | Baseline, week 4 | 
| Change From Baseline in Lung Clearance Index (LCI) After 1 Week | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | Baseline, week 1 | 
| Change of Lung Clearance Index (LCI) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | week 4, week 8 | 
| Change of Forced Expiratory Volume at 1 Second(FEV1) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry | week 4, week 8 | 
| Change of Colony-forming Units (CFU) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum. | week 4, week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Pseudomonas aeruginosa, Lung Clearance Index, Multiple Breath Washout, Inhaled Tobramycin, Inhaled Antibiotics.