Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)

Inclusion Criteria: * History of physician-diagnosed asthma * Methacholine PC20 less than or equal to 16 mg/ml and/or FEV1 improvement greater than or equal to 12% in response to 180 mcg albuterol * Stable asthma for at least 6 weeks prior to study entry * FEV1 greater than or equal to 60% of predicted result following 180 mcg albuterol * Juniper ACQ score greater than or equal to 1.5 (optimal ACQ score cut-off point for asthma that is "not well-controlled" by NIH/Global Initiative for Asthma \[GINA\] guidelines) * Nonsmoker (less than 10 pack-per-year lifetime smoking history and no smoking in the year prior to study entry) * Able to perform spirometry, as per American Thoracic Society criteria * 75% adherence with diary cards, fluticasone (monitored with Doser), and placebo pill trial (monitored electronically with Electronic Drug Exposure Monitor \[eDEM\] pill dose counter) for the final 2 weeks of the four-week run-in period * At Visit 1, in steroid-naïve participants, no significant adrenal suppression, defined as a plasma cortisol concentration less than 5 mcg/dL. If adrenal suppression occurs, a 250 mcg corticotropin (ACTH) stimulation test will be performed. Plasma cortisol levels will be collected at baseline, and 30 and 60 minutes after the ACTH stimulation test. Participants must have a cortisol concentration greater than 20 mcg/dL on at least one of the post-ACTH time points * Absence of bronchoscopy-induced exacerbation; if bronchoscopy-induced exacerbation has occurred, prednisone therapy must have stopped at least 6 weeks prior to study entry * Absence of respiratory tract infection; if infection has occurred, infection-related symptoms must have stopped at least 6 weeks prior to study entry * Has experienced no more than two exacerbations or respiratory tract infections prior to study entry * If female and able to conceive, willing to utilize two medically acceptable forms of contraception (one non-barrier method with single barrier method OR double barrier method) Exclusion Criteria: * Presence of lung disease other than asthma * Presence of vocal cord dysfunction, due to potential confounding of ACQ score * Significant medical illness other than asthma * History of atrial or ventricular tachyarrhythmia * Use of any medication that has a significant interaction with clarithromycin, including herbal or alternative therapies * Asthma exacerbation within 6 weeks of the screening visit or during the run-in period prior to bronchoscopy * Use of systemic steroids or change in dose of controller therapy within 6 weeks of the screening visit * Inability, in the opinion of the study investigator, to coordinate use of dry powder or metered-dose inhaler or to comply with medication regimens * Inability or unwillingness to perform required study procedures * Prolonged heart rate corrected QT-interval (greater than 450 msec in women and greater than 430 msec in men) on echocardiogram (ECG) at study entry * Low potassium or magnesium levels (based on local Asthma Clinical Research Network laboratory definitions) * Abnormal elevation of liver function tests (AST, ALT, total bilirubin, or alkaline phosphatase) * Abnormal prothrombin time (PT) or partial thromboplastin time (PTT) results * Reduced creatinine clearance * Contraindication to bronchoscopy, as determined by medical history or physical examination * Regular consumption of grapefruit or grapefruit juice * Pregnant or breastfeeding