Clinical trial NCT02449031: Observational Study in Cystic Fibrosis Patients Using TOBI® PODHALER® or Other FDA Approved Inhaled Antipseudomonal Antibacterial Drugs
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pseudomonas Aeruginosa in Cystic Fibrosis
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2015-05-20
Enrollment: 409
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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).

Primary outcomes:
measure: Absolute change in forced expiratory volume in one second (FEV1) percent predicted from baseline.
timeFrame: 1 year
measure: Absolute change from baseline in the number of P. aeruginosa colony forming units in sputum.
timeFrame: 1 year
measure: 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.
timeFrame: Up to 5 years
measure: 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.
timeFrame: Up to 5 years
measure: Number of pulmonary exacerbations and those leading to hospitalization.
timeFrame: 1 year
measure: Proportion of patients experiencing pulmonary exacerbations including those leading to hospitalization.
timeFrame: 1 year
measure: Incidence rate of patients with one or more pulmonary exacerbations.
timeFrame: 1 year
measure: Incidence rate of pulmonary exacerbations.
timeFrame: 1 year
measure: Time to first pulmonary exacerbation.
timeFrame: 1 year
measure: Use of additional antipseudomonal antibiotics (overall, IV, oral) to treat pulmonary exacerbations.
timeFrame: 1 year
measure: Mortality rate
timeFrame: 1 year
measure: Pharmacokinetic properties of TOBI® PODHALER® as measured by sputum specimens collected during the on-treatment cycles.
timeFrame: 1 year
measure: Number of respiratory related hospitalizations.
timeFrame: 1 year
measure: Duration of stay for respiratory related hospitalizations.
timeFrame: 1 year
measure: Number of non-respiratory related hospitalizations.
timeFrame: 1 year
measure: Duration of stay for non-respiratory related hospitalizations.
timeFrame: 1 year
Secondary outcomes:
measure: Relative change in FEV1 % predicted from baseline.
timeFrame: 1 year
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Novartis Investigative Site
state: Alaska
city: Little Rock
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Bellflower
country: United States
facility: Novartis Investigative Site
state: California
city: Fullerton
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Madera
country: United States
facility: Novartis Investigative Site
state: California
city: Hartford
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: New Haven
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Stamford
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Gainesville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Boise
country: United States
facility: Novartis Investigative Site
state: Idaho
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Iowa City
country: United States
facility: Novartis Investigative Site
state: Iowa
city: New Orleans
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Grand Rapids
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Ypsilanti
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Jackson
country: United States
facility: Novartis Investigative Site
state: Mississippi
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Billings
country: United States
facility: Novartis Investigative Site
state: Montana
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Lebanon
country: United States
facility: Novartis Investigative Site
state: New Hampshire
city: New Brunswick
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: New Hyde Park
country: United States
facility: Novartis Investigative Site
state: New York
city: Winston-Salem
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Akron
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Hershey
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Sioux Falls
country: United States
facility: Novartis Investigative Site
state: South Dakota
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Tyler
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Burlington
country: United States
facility: Novartis Investigative Site
state: Vermont
city: Norfolk
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Richmond
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
Study officials:
References: