Azithromycin in Patients With CF, Infected With Burkholderia Cepacia Complex

STUDY DESIGN

• Overview
• This is a single center, randomized, double-blinded, placebo-controlled 24 week trial of azithromycin in adults with CF chronically infected with BCC. The investigational therapy will be added to usual therapy in patients who are clinically stable at the time of enrollment. After 168 days, the study drug will be discontinued and participants will be evaluated at 196 days off of study drug for 28 days. At that visit, participants will be invited to continue in an open label observational study of azithromycin for 168 additional days. Thus, the duration of the study will be 52 weeks (364 days).
• Day 0- Day 168 on Study Drug (24 weeks)
• Day 169- Day 196 off Study Drug (4 weeks)
• Day 197 - Day 364 on OPEN label Azithromycin (24 weeks)
• Measuring primary and secondary endpoints
• Primary efficacy endpoint
• Primary efficacy endpoint will be the quantitative changes in lung function as measured by FEV1 in % predicted from baseline to completion of the 24 week treatment period. (refer to Appendix C for ATS guidelines).
• Primary safety endpoints

• Primary safety endpoints collected over the 24 week treatment period will be:

  • Adverse events such as gastrointestinal complaints, ototoxicity, tinnitus, hepatitis or leukopenia as determined by:

    (i) open ended questioning of study subjects at study visits (ii) laboratory tests for elevated liver function tests or hematologic abnormalities,

  • Changes in lung microbiology as determined by:[86] (i) Emergent B. cenocepacia (genomovar III) (ii) Emergent non-B. cenocepacia genomovars (iii) Emergent NTM[87] (iv) Emergent azithromycin resistant NTM (v) Emergent Aspergillus species (vi) Emergent MDRO - (S. maltophilia, A. xylosoxidans, or methicillin-resistant S. aureus) (vii) Emergent P. aeruginosa (viii) Emergent azithromycin resistant S. aureus
• Secondary efficacy endpoints
• Secondary efficacy endpoints will be:
• Quantitative changes in lung function as measured by change in relative percent change in FEV1 and FVC from baseline to completion of the 24 week treatment period.
• Quantitative change in FEV1 and FVC in liters in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo. FEV1 and FVC in liters will be measured according to ATS criteria
• The number of days until first administration of intravenous antibiotics and/or the use of oral tetracycline derivatives minocycline / doxycycline for seven or more days during the 24 week period.
• The number of pulmonary exacerbations as defined by need for treatment with intravenous or oral tetracycline derivative antibiotics for an increase in pulmonary symptoms during the 24 week period.
• The proportion of patients requiring intravenous antibiotics during the 24 week period.
• The number of days of treatment with intravenous antibiotics given during the 24 week period.
• The proportion of patients hospitalized.
• The number of hospital days as calculated by calendar days during the 24 week period.
• The proportion of patients requiring oral antibiotics during the 24 week period.
• The number of days of treatment with oral non-tetracycline derivative antibiotics given during the 24 week period.
• Changes in body weight from baseline to completion of the 24 week treatment period.
• Change in level of inflammation as measured by the change in serum CRP and ESR from baseline to the end of the 24 week treatment period.