OPTIMIZing Treatment for Early Pseudomonas Aeruginosa Infection in Cystic Fibrosis

• Status: Completed
• Trial end date: 2018-08-23
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this trial is to compare the effects of treatment with tobramycin solution for inhalation (TIS) with and without azithromycin in people with cystic fibrosis (CF) age 6 months to 18 years who have early isolation of Pseudomonas aeruginosa (Pa) from a respiratory culture. Specimens of blood and sputum or throat swabs will be taken during the study along with pulmonary function testing. Participants will receive initial treatment with TIS followed additional treatment with TIS if quarterly respiratory cultures are positive for Pa in addition to either azithromycin or placebo for 18 months.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bonnie Ramsey
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Azithromycin; Pharmaceutical Solutions; Tobramycin

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