Observational Study in Cystic Fibrosis Patients Using TOBI® PODHALER® or Other FDA Approved Inhaled Antipseudomonal Antibacterial Drugs

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, prospective, two cohort, observational study over a 5-year period in Cystic Fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection.The study will collect data over 1 year on respiratory function, antibacterial effectiveness, and clinical outcomes of treatment with inhaled antipseudomonal antibiotics and data over 5 years on microbiological and safety assessments.

Detailed Description
-----------------
This study will include CF patients chronically colonized with P. aeruginosa enrolled in the Cystic Fibrosis Foundation (CFF) PortCF registry and using TOBI® PODHALER® or another FDA-approved inhaled antipseudomonal antibiotic. No therapeutic intervention will be assigned and physicians will use their discretion in choosing a treatment regimen for their patients. Sputum samples (primarily collected during routine clinical follow-up) from patients able to spontaneously produce sputum will be sent to a central laboratory for analysis. In addition, this study will include two optional sub-studies for qualifying patients in the first study year - Sputum microbiology sub-study and TOBI® PODHALER® sputum pharmacokinetics (PK) sub-study.

Official Title
-----------------
A Prospective Observational Study in Cystic Fibrosis Patients With Chronic Respiratory Pseudomonas Aeruginosa Infection Treated With TOBI® PODHALER® (Tobramycin Inhalation Powder) or Other FDA Approved Inhaled Antipseudomonal Antibacterial Drugs

Conditions
-----------------
Pseudomonas Aeruginosa in Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: TOBI® PODHALER®
* Drug: TOBI®
* Drug: Bethkis®
* Drug: Cayston®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 6 years of age. Documented FEV1 ≥ 25% predicted in the previous year. Diagnosis of cystic fibrosis. Established diagnosis of chronic P. aeruginosa infection of the lungs defined as two or more positive P. aeruginosa cultures in the previous year as documented in the subject's medical history (this may include a history of one positive culture in the year prior to enrollment and one positive culture from the specimen collected at the baseline visit). Prescribed and initiated chronic treatment with FDA-approved inhaled antipseudomonal antibiotic for chronic P. aeruginosa infection (e.g. TOBI® PODHALER®, TOBI®, Cayston® and Bethkis®). Actively enrolled or willingness to enroll in PortCF registry. Willing and able to provide written informed consent or, parent/guardian consent and where applicable pediatric assent, for participation and use of relevant clinical data previously captured in PortCF. Anticipated to have good adherence to routine visits, defined as the investigator having good knowledge that the patient has been to at least 2-3 routine visits in the previous year. Exclusion Criteria: Documented FEV1 < 25% predicted in the previous year. Current participation in an interventional clinical study with an inhaled antibiotic treatment. Treatment with compounded tobramycin (e.g. the use of tobramycin IV solution adapted for use by inhalation). Treatment with inhaled antipseudomonal antibacterial drug(s) that are not FDA approved. Patients undergoing an early eradication regimen for CF (first line therapy).

Ages Eligible for Study
-----------------
Minimum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TOBI® PODHALER® cohort<br> | Drug: TOBI® PODHALER®<br> <br> |
| non-TOBI® PODHALER® cohort<br>Approximately 250 patients treated with other FDA-approved inhaled antipseudomonal antibacterial drugs at enrollment | Drug: TOBI®<br>* tobramycin inhalation solution, USP<br>Drug: Bethkis®<br>* tobramycin inhalation solution<br>Drug: Cayston®<br>* aztreonam for inhalation solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in forced expiratory volume in one second (FEV1) percent predicted from baseline. |  | 1 year | 
| Absolute change from baseline in the number of P. aeruginosa colony forming units in sputum. |  | 1 year | 
| Minimum inhibitory concentration (MIC) of tobramycin and the following antipseudomonal antibacterial drugs (meropenem, imipenem, ceftazidime, aztreonam and ciprofloxacin) for P. aeruginosa sputum isolates in both treatment cohorts. |  | Up to 5 years | 
| Frequency of the following treatment emergent pathogens in sputum: S. aureus (MRSA and MSSA), S. maltophilia, A. xylosoxidans, and Burkholderia spp.in both treatment cohorts. |  | Up to 5 years | 
| Number of pulmonary exacerbations and those leading to hospitalization. |  | 1 year | 
| Proportion of patients experiencing pulmonary exacerbations including those leading to hospitalization. |  | 1 year | 
| Incidence rate of patients with one or more pulmonary exacerbations. |  | 1 year | 
| Incidence rate of pulmonary exacerbations. |  | 1 year | 
| Time to first pulmonary exacerbation. |  | 1 year | 
| Use of additional antipseudomonal antibiotics (overall, IV, oral) to treat pulmonary exacerbations. |  | 1 year | 
| Mortality rate |  | 1 year | 
| Pharmacokinetic properties of TOBI® PODHALER® as measured by sputum specimens collected during the on-treatment cycles. |  | 1 year | 
| Number of respiratory related hospitalizations. |  | 1 year | 
| Duration of stay for respiratory related hospitalizations. |  | 1 year | 
| Number of non-respiratory related hospitalizations. |  | 1 year | 
| Duration of stay for non-respiratory related hospitalizations. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in FEV1 % predicted from baseline. |  | 1 year |