AZMATICS: AZithroMycin/Asthma Trial In Community Settings
Condition: Asthma
MeSH terms: Asthma
Intervention: Azithromycin; Placebo
Intervention description: 600 mg x 3 days, then 600 mg weekly x 11 weeks; Matching placebo
Intervention MeSH terms: Azithromycin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 2 arms are randomized, placebo-controlled, double-blinded, 1 arm was added as an open-label observational cohort
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Randomized clinical trial; Asthma; Adults; Azithromycin

Summary:

      The purpose of this study is to assess the effectiveness of the azalide macrolide
      azithromycin in adults with persistent asthma.

      Research Question: Will a 12-week treatment with the antibiotic, azithromycin, result in a
      statistically significant and clinically meaningful improvement in overall asthma symptoms
      and other patient-oriented asthma outcomes one year after initiation of treatment of adult
      primary care patients with asthma?

      Experimental Design: The investigators propose a one-year randomized, placebo-controlled,
      blinded (investigator, patient, data collector, data analyst) trial of 12 weekly doses of
      azithromycin/placebo as adjunctive therapy (in addition to usual care) along with a parallel
      observational cohort who will participate 'open label' in 100 adult asthma patients recruited
      from practice-based research networks (e.g., Wisconsin Research and Education Network (WREN)
      and others). This "practical clinical trial" will (1) enroll a representative sample of
      asthma patients encountered in the practices of primary care physicians, (2) employ standard
      clinical trial methodology to ensure internally valid results and (3) measure outcomes
      important to patients, so that the results will be valid and applicable to the kinds of
      asthma patients encountered by family physicians and other primary care providers.

      Active study sites -

        -  Wisconsin: Augusta, Cross Plains, La Crosse, Marshfield, Milwaukee, Madison,

        -  Mauston, Rice Lake, Tomah, Wausau

        -  Colorado: Monument

        -  Illinois: Peoria

        -  Nevada: Reno

        -  North Carolina: Granite Falls

        -  North Dakota: Minot

        -  Ohio: Cleveland, Berea

        -  Oklahoma: Ardmore, Claremore, Edmond, Lawton, Oklahoma City, Stroud, Tulsa, Weatherford

        -  Rhode Island: East Providence
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 and older (and at least 50 kg/110 pounds)

               -  The lower weight limit was chosen to avoid exposure to greater than 12 mg/kg/day
                  of azithromycin (a currently recommended dose for children)

               -  We specify no upper age limit because asthma occurs throughout the age range and
                  because asthma in the elderly is particularly severe and warrants inclusion.

          -  Physician-diagnosed asthma

          -  At the time of randomization, eligible subjects must either:

               -  be having a documented asthma exacerbation OR

               -  be reporting at least mild persistent asthma symptoms, as defined by GINA (Global
                  Initiative for Asthma)

          -  Subjects must also have asthma symptoms for at least six months prior to randomization

          -  Documentation of objective evidence of reversible airway obstruction, either
             spontaneously or after treatment, is required prior to randomization. This requirement
             can be met by documentary evidence, within 2 years of randomization, of either:

               -  a 12% or greater (and ≥200 mL) change in FEV1 OR

               -  a 25% or greater (and >60 L/min) change in PEFR either spontaneously or as a
                  result of treatment

        Exclusion Criteria:

          -  Not English literate or without email and internet access

          -  Macrolide allergy

          -  Pregnancy or lactation

          -  Females of childbearing potential must agree to use an acceptable form of
             contraception during the treatment period

          -  Chronic use of macrolides, tetracyclines or quinolones Chronic use is defined as 4 or
             more weeks of continuous use within 6 months of randomization

          -  Asthma symptoms for less than 6 months prior to randomization Asthma symptoms must be
             present for at least 6 months to exclude patients without true chronic asthma

          -  Unstable asthma requiring immediate emergency care All patients with asthma
             exacerbations will receive usual urgent or emergency care for asthma and must be
             improving or stable in the judgment of the treating physician prior to being enrolled

          -  Specified co-morbidities likely to interfere with study assessments or follow up.
             Excluded comorbidities include:

               -  cystic fibrosis

               -  obstructive sleep apnea requiring CPAP

               -  cardiomyopathy

               -  congestive heart failure

               -  terminal cancer

               -  alcohol or other drug abuse

               -  or any other serious medical condition that, in the opinion of the study
                  physician, would seriously interfere with or preclude assessment of study
                  outcomes or completion of study assessments

          -  Specified medical conditions for which macrolide administration may possibly be
             hazardous

          -  Patients with acute or chronic hepatitis, cirrhosis or other liver disease, chronic
             kidney disease, or history of prolonged cardiac repolarization and QT interval or
             torsades de pointes, are excluded

          -  Specified medications for which close monitoring has been recommended in the setting
             of macrolide administration Patients taking digoxin, theophylline, warfarin,
             ergotamine or dihydroergotamine, triazolam, carbamazepine, cyclosporine, hexobarbital
             or phenytoin are excluded.

               -  If any of these medications are started after randomization and before completion
                  of the 12-week treatment phase, study medication will be discontinued and the
                  patient may remain in the study.

        The intent of this protocol is to enroll a broadly generalizable sample of adult patients
        with physician-diagnosed asthma, either stable persistent or in exacerbation.