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

• ClinicalTrials.gov Identifier: NCT02449031
• Recruitment Status: Completed
• First Posted: May 20, 2015
• Last Update Posted: March 22, 2022
• Sponsor: Mylan Inc.
• Collaborator: Cystic Fibrosis Foundation
• Information provided by (Responsible Party): Viatris Inc. ( Mylan Inc. )

Study Description

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.

Condition or disease	Intervention/treatment
Pseudomonas Aeruginosa in Cystic Fibrosis	Drug: TOBI® PODHALER®; Drug: TOBI®; Drug: Bethkis®; Drug: Cayston®

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.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 409 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 5 Years
• 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
• Actual Study Start Date: May 5, 2015
• Actual Primary Completion Date: December 31, 2021
• Actual Study Completion Date: December 31, 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
TOBI® PODHALER® cohort	Drug: TOBI® PODHALER®
non-TOBI® PODHALER® cohort; Approximately 250 patients treated with other FDA-approved inhaled antipseudomonal antibacterial drugs at enrollment	Drug: TOBI®; tobramycin inhalation solution, USP; Drug: Bethkis®; tobramycin inhalation solution; Drug: Cayston®; aztreonam for inhalation solution

Outcome Measures

Primary Outcome Measures :

1. Absolute change in forced expiratory volume in one second (FEV1) percent predicted from baseline. [ Time Frame: 1 year ]
2. Absolute change from baseline in the number of P. aeruginosa colony forming units in sputum. [ Time Frame: 1 year ]
3. 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. [ Time Frame: Up to 5 years ]
4. 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. [ Time Frame: Up to 5 years ]
5. Number of pulmonary exacerbations and those leading to hospitalization. [ Time Frame: 1 year ]
6. Proportion of patients experiencing pulmonary exacerbations including those leading to hospitalization. [ Time Frame: 1 year ]
7. Incidence rate of patients with one or more pulmonary exacerbations. [ Time Frame: 1 year ]
8. Incidence rate of pulmonary exacerbations. [ Time Frame: 1 year ]
9. Time to first pulmonary exacerbation. [ Time Frame: 1 year ]
10. Use of additional antipseudomonal antibiotics (overall, IV, oral) to treat pulmonary exacerbations. [ Time Frame: 1 year ]
11. Mortality rate [ Time Frame: 1 year ]
12. Pharmacokinetic properties of TOBI® PODHALER® as measured by sputum specimens collected during the on-treatment cycles. [ Time Frame: 1 year ]
13. Number of respiratory related hospitalizations. [ Time Frame: 1 year ]
14. Duration of stay for respiratory related hospitalizations. [ Time Frame: 1 year ]
15. Number of non-respiratory related hospitalizations. [ Time Frame: 1 year ]
16. Duration of stay for non-respiratory related hospitalizations. [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. Relative change in FEV1 % predicted from baseline. [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

CF patients chronically colonized with P. aeruginosa enrolled in the Cystic Fibrosis Foundation (CFF) PortCF registry and using TOBI® PODHALER® (TOBI® PODHALER®-treated cohort) or another FDA-approved inhaled antipseudomonal antibiotic (non-TOBI® PODHALER®-treated cohort).

It is anticipated that this patient population will include a subset of patients with increased P. aeruginosa MICs to tobramycin at baseline.

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).

Contacts and Locations

Locations

United States, Alaska

Novartis Investigative Site

Anchorage, Alaska, United States, 99508

United States, Arkansas

Novartis Investigative Site

Little Rock, Arkansas, United States, 72202

United States, California

Novartis Investigative Site

Bellflower, California, United States, 90706

Novartis Investigative Site

Fullerton, California, United States, 92831

Novartis Investigative Site

Los Angeles, California, United States, 90027

Novartis Investigative Site

Madera, California, United States, 93636

United States, Connecticut

Novartis Investigative Site

Hartford, Connecticut, United States, 06102

Novartis Investigative Site

New Haven, Connecticut, United States, 06519

Novartis Investigative Site

Stamford, Connecticut, United States, 06902

United States, Florida

Novartis Investigative Site

Gainesville, Florida, United States, 32610

Novartis Investigative Site

Miami, Florida, United States, 33136

Novartis Investigative Site

Orlando, Florida, United States, 32803

Novartis Investigative Site

Tampa, Florida, United States, 33606

United States, Georgia

Novartis Investigative Site

Atlanta, Georgia, United States, 30322

United States, Idaho

Novartis Investigative Site

Boise, Idaho, United States, 83712

United States, Illinois

Novartis Investigative Site

Chicago, Illinois, United States, 60611

United States, Indiana

Novartis Investigative Site

Indianapolis, Indiana, United States, 46202-5225

United States, Iowa

Novartis Investigative Site

Iowa City, Iowa, United States, 52242

United States, Louisiana

Novartis Investigative Site

New Orleans, Louisiana, United States, 70112

United States, Massachusetts

Novartis Investigative Site

Boston, Massachusetts, United States, 02115

United States, Michigan

Novartis Investigative Site

Detroit, Michigan, United States, 97205

Novartis Investigative Site

Grand Rapids, Michigan, United States, 49503

Novartis Investigative Site

Ypsilanti, Michigan, United States, 48197

United States, Mississippi

Novartis Investigative Site

Jackson, Mississippi, United States, 39216

United States, Missouri

Novartis Investigative Site

Kansas City, Missouri, United States, 64108

United States, Montana

Novartis Investigative Site

Billings, Montana, United States, 59101

United States, Nebraska

Novartis Investigative Site

Omaha, Nebraska, United States, 68198

United States, New Hampshire

Novartis Investigative Site

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Novartis Investigative Site

New Brunswick, New Jersey, United States, 8901

United States, New York

Novartis Investigative Site

New Hyde Park, New York, United States, 11040

United States, North Carolina

Novartis Investigative Site

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Novartis Investigative Site

Akron, Ohio, United States, 44308-1062

United States, Oklahoma

Novartis Investigative Site

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Novartis Investigative Site

Hershey, Pennsylvania, United States, 17033-085

Novartis Investigative Site

Philadelphia, Pennsylvania, United States, 19104

Novartis Investigative Site

Philadelphia, Pennsylvania, United States, 19107

United States, South Carolina

Novartis Investigative Site

Charleston, South Carolina, United States, 29425

United States, South Dakota

Novartis Investigative Site

Sioux Falls, South Dakota, United States, 57104

United States, Tennessee

Novartis Investigative Site

Nashville, Tennessee, United States, 37232

United States, Texas

Novartis Investigative Site

Austin, Texas, United States, 78723

Novartis Investigative Site

Dallas, Texas, United States, 75390

Novartis Investigative Site

Tyler, Texas, United States, 75708

United States, Utah

Novartis Investigative Site

Salt Lake City, Utah, United States, 84132

United States, Vermont

Novartis Investigative Site

Burlington, Vermont, United States, 5405

United States, Virginia

Novartis Investigative Site

Norfolk, Virginia, United States, 23507

Novartis Investigative Site

Richmond, Virginia, United States, 23298

United States, Washington

Novartis Investigative Site

Spokane, Washington, United States, 99204

Sponsors and Collaborators

Mylan Inc.

Cystic Fibrosis Foundation

More Information

Additional Information:

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT02449031
• Other Study ID Numbers: CTBM100C2407
• First Posted: May 20, 2015
• Last Update Posted: March 22, 2022
• Last Verified: March 2022

Additional relevant MeSH terms:

Pseudomonas Infections; Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Tobramycin; Anti-Bacterial Agents; Anti-Infective Agents