Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)
Condition: Asthma
MeSH terms: Asthma
Intervention: clarithromycin; fluticasone propionate; placebo clarithromycin
Intervention description: clarithromycin 500 mg twice daily (Biaxin); fluticasone propionate 88 mcg twice daily (Flovent® HFA 44 mcg two puffs twice daily); placebo clarithromycin twice daily
Intervention MeSH terms: Fluticasone; Xhance; Clarithromycin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 92.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      Asthma can be caused by a variety of factors, including tobacco smoke, allergens, and
      respiratory airway infections. Many people use inhaled corticosteroid medications to treat
      their symptoms. These medications, however, are not effective for everyone. Clarithromycin is
      an antibiotic that may effectively treat asthma in these individuals. This study will
      evaluate the effectiveness of clarithromycin at controlling asthma symptoms.
    

Eligibility criteria:

        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