OPTIMIZing Treatment for Early Pseudomonas Aeruginosa Infection in Cystic Fibrosis (OPTIMIZE)
Cystic Fibrosis
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic fibrosis (CF), Azithromycin, Tobramycin solution for inhalation (TIS), Pseudomonas aeruginosa (Pa), Early Pseudomonas aeruginosa infection, Pulmonary exacerbation, Standardized anti-pseudomonal therapy
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 6 months to ≤ 18 years
- Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype or positive CF Newborn Screening result for immunoreactive trypsinogen (IRT) IRT/DNA or IRT/IRT and one or more of the following criteria:
- sweat chloride ≥ 60 milliequivalent (mEq)/liter by quantitative by pilocarpine iontophoresis test (QPIT)
- two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
- Abnormal nasal potential difference (NPD) (change in NPD in response to a low chloride solution and isoproteronol of less than - 5 mV)
- Documented new positive oropharyngeal, sputum or lower respiratory tract culture for Pa within 30 days of the Baseline Visit (Visit 1), defined as: a) first lifetime documented Pa positive culture; or b) Pa recovered after at least a two-year history of Pa negative respiratory cultures (≥ 1 culture/ year)
- Clinically stable with no evidence of any significant respiratory symptoms at the Baseline Visit that would require administration of intravenous anti- pseudomonal antibiotics, oxygen supplementation, and/or hospitalization as determined by the study physician
- Written informed consent obtained from participant or participant's legal representative (and assent when applicable) and ability for participant to comply with the requirements of the study
Exclusion Criteria:
- Macrolide antibiotic use within 30 days of the Baseline Visit
- Initiation of current course of treatment with TIS >14 days prior to Baseline Visit
- Weight <6.0 kg at the Baseline Visit
- History of aminoglycoside hypersensitivity or adverse reaction to inhaled aminoglycoside
- History of azithromycin hypersensitivity or adverse reaction to azithromycin or allergy to macrolide antibiotics
- History of positive respiratory culture for Non-tuberculous mycobacteria (NTM) or Burkholderia cepacia complex within 2 years of the Baseline Visit
- History of unresolved, abnormal renal function (defined as serum creatinine greater than 1.5 times the upper limit of normal for age).
- History of unresolved, abnormal liver function tests (defined as alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than 4 times the upper limit of normal range) or history of portal hypertension
- History of unresolved, abnormal neutropenia (ANC ≤ 1000)
- Abnormal ECG test at the Baseline Visit defined as a QT interval corrected (QTc) (B) of ≥460 msec or history of ventricular arrhythmia
- History of abnormal hearing sensitivity defined as hearing threshold levels >25 dB HL (decibels Hearing Level) for visual reinforcement audiometry (VRA) at any frequency (500-4000Hz) or >20 Decibels Hearing Level (dBHL) for play or standard audiometry at any two frequencies (500-8000Hz) in either ear, not associated with middle ear disease (including infection) or a flat (Type B) tympanogram
- New initiation of chronic therapy (greater than 21 days) with drugs known to prolong QT interval (refer to Appendix III) within 30 days prior to the Baseline Visit or coadministration of nelfinavir or oral anticoagulants
- Positive serum or urine pregnancy test at the Baseline Visit (to be performed on all females of child-bearing potential) or for females of child bearing potential: pregnant, breastfeeding, or unwilling to use barrier contraception during participation in the study
- Administration of any investigational drug within 30 days prior to the Baseline Visit
- Presence of a condition or abnormality (e.g., pre-existing heart disease) that in the opinion of the site investigator would compromise the safety of the participant or the quality of the data
Sites / Locations
- CFF Affiliate Program Providence Medical Center
- CFF Care Center Arizona Health Science Center
- CFF Care Center & Pediatric Program Arkansas Children's Hospital
- Childrens Hospital Los Angeles
- CFF Care Center & Pediatric Program Stanford University
- CFF Care Center & Pediatric Program Children's Hospital Colorado
- CFF Care Center & Pediatric Program Yale University
- CFF Care Center & Pediatric Program Nemours Children's Clinic - Jacksonville
- CFF Care Center & Pediatric Program All Children's Hospital
- CFF Care Center & Pediatric Program Emory University
- CFF Affiliate Program Children's Healthcare of Atlanta
- CFF Care Center St. Luke's CF Clinic
- CFF Care Center & Pediatric Program Ann & Robert H. Lurie Children's Hospital of Chicago
- CFF Care Center & Pediatric Program Riley Hospital for Children
- CFF Care Center & Pediatric Program University of Iowa
- CFF Care Center & Pediatric Program Maine Medical Center
- CFF Care Center & Pediatric Program Children's Hospital Boston
- CFF Care Center & Pediatric Program University of Michigan
- CFF Care Center & Pediatric Program Children's Hospital of Michigan
- CFF Care Center The Children's Mercy Hospital
- CFF Care Center & Pediatric Program Cardinal Glennon Children's Hospital/Saint Louis University
- CFF Care Center & Pediatric Program St. Louis Children's Hospital
- CFF Care Center & Pediatric Program University of Nebraska Medical Center
- CFF Care Center & Pediatric Program Monmouth Medical Center
- CFF Care Center & Pediatric Program Columbia University
- CFF Care Center & Pediatric Program SUNY Upstate Medical University
- CFF Care Center New York Medical College
- CFF Care Center & Pediatric Program University of North Carolina at Chapel Hill
- CFF Care Center & Pediatric Program Akron Children's Hospital
- CFF Care Center & Pediatric Program Cincinnati Children's Hospital Medical Center
- CFF Care Center & Pediatric Program Rainbow Babies and Children's Hospital
- CFF Care Center & Pediatric Program Nationwide Children's Hospital
- CFF Care Center & Pediatric Program The Children's Medical Center
- CFF Care Center & Pediatric Program Oregon Health & Sciences University
- CFF Care Center & Pediatric Program Hershey Medical Center
- CFF Care Center & Pediatric Program Children's Hospital of Pittsburgh
- CFF Care Center & Pediatric Program Sanford USD Medical Center
- CFF Care Center & Pediatric Program University of Tennessee
- CFF Care Center & Pediatric Program Dell Children's Medical Center of Central Texas
- University of Utah
- CFF Care Center & Pediatric Program Children's Hospital of the King's Daughters
- CFF Care Center Medical College of Virginia
- CFF Care Center & Pediatric Program Seattle Children's Hospital
- CFF Care Center & Pediatric Program University of Wisconsin
- CFF Care Center & Pediatric Program Children's Hospital of Wisconsin
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
azithromycin and TIS
placebo and TIS
azithromycin and tobramycin solution for inhalation (TIS) Azithromycin 3 times weekly, oral suspension, 10 mg/kg/dose up to 500 mg, for 18 months Tobramycin solution for inhalation (TIS), 300 mg, twice daily for 28 days when respiratory cultures are found positive for Pa at study visits for 18 months
placebo and tobramycin solution for inhalation (TIS) Placebo 3 times weekly, oral suspension, volume-matched to azithromycin, for 18 months Tobramycin solution for inhalation (TIS), 300 mg, twice daily for 28 days when respiratory cultures are found positive for Pa at study visits for 18 months