Please select the eligibility criteria that correspond to the clinical trial below.
Title: OPTIMIZing Treatment for Early Pseudomonas Aeruginosa Infection in Cystic Fibrosis: The OPTIMIZE Multicenter, Placebo-Controlled, Double-Blind, Randomized Trial
Brief 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.


Options:
A: 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
B: Inclusion Criteria:

* Male or female ≥12 years of age at Visit 1
* Enrolled in the CFFNPR (Patients may enroll in the Registry at Visit 1 if not previously enrolled.)
* Current hospitalization for treatment of a pulmonary exacerbation
* Planned hospital admission of at least 5 days with intravenous (IV) antibiotics at Visit 1
* Able to perform spirometry at admission and willing to perform spirometry on subsequent treatment and visit days
* Willing and able to complete symptom score daily
* Willing to return for a follow up visit at end of treatment (if necessary) and 28 days after start of IV antibiotic therapy
* Written informed consent (and assent when applicable) obtained from the participant or participant's legal representative

Exclusion Criteria:

* Previous enrollment in this study
* Treatment with IV antibiotics in the 6 weeks prior to Visit 1
* Admission to the intensive care unit for current pulmonary exacerbation
* Pneumothorax on admission
* Current hospitalization for scheduled pulmonary clean out
* Current hospitalization for sinusitis as the primary diagnosis
* Massive hemoptysis defined as \> 250 cc in a 24 hour period, or 100 cc/day over 4 consecutive days occurring within one week of Visit 1
* Current pulmonary exacerbation thought to be due to allergic bronchopulmonary aspergillosis (ABPA)
* Ongoing treatment with prednisone equivalent \>10 mg/day for greater than 2 weeks initiated prior to Visit 1
* History of solid organ transplantation Currently receiving antimicrobial therapy to treat non-tuberculous mycobacterium (e.g., M. abscessus, M. avium complex)
C: Inclusion Criteria:

* Participants ≥ 6 years of age
* Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

  * Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
  * Two well characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
  * Abnormal nasal potential difference
* PA present in expectorated sputum or throat swab culture at Visit 1 OR documented PA in 2 expectorated sputum or throat swab cultures within the 12 months prior to Visit 1 (one of the previous PA positive cultures must have been no more than 3 months prior to Visit 1)
* FEV1 \> 75% predicted at Visit 1
* Participants must have exhibited two or more of the following chronic and/or intermittent CF symptoms, for a minimum of 28 days prior to randomization and with no worsening of symptoms within 7 days prior to randomization:

  * Chest congestion
  * Daily cough
  * Productive cough
  * Wheezing
  * Trouble breathing
  * Nocturnal wakening due to coughing
* Participants (and parent/guardian as required) had to be able to provide written informed consent/assent prior to any study related procedures
* Females of childbearing potential had to have a negative urine pregnancy test at Visit 1
* Ability to perform reproducible pulmonary function tests
* In the opinion of the Investigator, the participant did not require immediate antipseudomonal antibiotic intervention to treat an impending exacerbation, and the participant's condition was stable enough to enroll in the study

Exclusion Criteria:

* Administration of any investigational drug or device within 28 days prior to Visit 1 or within 6 half-lives of the investigational drug (whichever was longer)
* Administration of any IV, oral, or inhaled antipseudomonal antibiotic within 28 days prior to Visit 1
* Known local or systemic hypersensitivity to monobactam antibiotics
* Inability to tolerate short-acting bronchodilator (BD) use at least TID
* Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
* Changes in or initiation of chronic hypertonic saline treatment within 28 days prior to Visit 1
* Changes in or initiation of dornase alfa within 28 days prior to Visit 1
* Changes in antimicrobial, BD, or corticosteroid medications within 7 days prior to Visit 1
* Changes in physiotherapy technique or schedule within 7 days prior to Visit 1
* History of lung transplantation
* History of participation (enrollment) in any prior clinical studies with AZLI
* A chest radiograph at Visit 1 (or within the previous 180 days of Visit 1), with abnormalities indicating a significant acute finding (e.g., lobar infiltrate and atelectasis, pneumothorax, or pleural effusion); a chest radiograph obtained and interpreted between Visits 1 and 2 was also acceptable for determining eligibility
* Positive urine pregnancy test at Visit 1; all women of childbearing potential were to be tested
* Females of childbearing potential who were lactating or were not (in the opinion of the investigator) practicing an acceptable method of birth control; female participants who utilized hormonal contraceptives as their birth control method must have used the same method for at least 3 months before study dosing
* Participant was being assessed at Visit 1 by the investigator for an acute change in respiratory symptoms
* Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would have interfered with participant treatment, assessment, or compliance with the protocol
D: Inclusion Criteria (selected):

* \>/= 12 years of age
* Confirmed Diagnosis of Cystic Fibrosis
* Positive sputum culture for P. aeruginosa at screening and within the past 12 months
* Patients are able to elicit an FEV1 \>/= 25% but \</= 85% of predicted value at screening
* Have received at least 3 courses of inhaled antimicrobials over the preceding 12 months
* Clinically stable with no changes in health status within the last 28 days
* Able to reproducibly produce sputum and perform spirometry

Exclusion Criteria (selected):

* Use of any nebulized or systemic antibiotics within 28 days prior to baseline
* History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication
* Evidence of respiratory infections within 14 days prior to dosing
* CrCl \< 20ml/min or \< 20ml/min/1.73 m2 at Screening

Answer: A