Intervention: Azithromycin
Trial phase: Phase 3
ATC code: J01FA10 | J01RA07 | J01RA16 | S01AA26
SMILES: CCC1OC(=O)C(C)C(OC2CC(C)(OC)C(O)C(C)O2)C(C)C(OC2OC(C)CC(N(C)C)C2O)C(C)(O)CC(C)CN(C)C(C)C(O)C1(C)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 22
Group description: Eligible participants who refused randomization were offered enrollment in an open-label azithromycin arm
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.