AZithromycin Against pLacebo in Exacerbations of Asthma (AZALEA)

• Quality of life [ Time Frame: 5 & 10 days post randomisation ] [ Designated as safety issue: Yes ]
  • Health status assessed by acute asthma QolQ (Juniper)
  • Health status assessed by Mini Asthma QolQ (Juniper)
• Time to 50% reduction in symptom score [ Time Frame: From Visit 1 (day 1) to Visit 4 (day 42) ] [ Designated as safety issue: No ]
• Pulmonary Function tests [ Time Frame: 5 & 10 days post randomisation ] [ Designated as safety issue: Yes ]
  Pulmonary function tests include: FEV1, FVC, FEV1/FVC ratio, PEF, FEF25-75% and FEF50%

Acute attacks (exacerbations) of asthma are common and cause a great deal of suffering in asthmatic patients. Current treatments for asthma attacks are not completely effective and new and better treatments are needed. Viruses often cause asthma attacks and bacterial lung infections have also been associated with asthma attacks. However, the role for bacteria is uncertain. Current asthma guidelines for doctors treating asthma exacerbations do not recommend the routine use of antibiotics. The investigators would like to investigate whether or not azithromycin, which is a safe and well tolerated antibiotic (an antibacterial) that has been used for many years in the treatment of respiratory disease, might be of benefit in asthma attacks. As there is some evidence that azithromycin has anti-viral properties this may add to its benefits (antibiotics don't usually affect viruses). By looking at the effect of azithromycin on asthma attacks this will help us to show whether or not azithromycin should be recommended during an acute asthma attack in addition to the usual care that is provided to these patients as it may help them recover quicker from the exacerbation. The investigators will also be able to look at why azithromycin may be effective - if it is having an anti-bacterial and/or anti-viral effect.

• Drug: Zithromax
  250mg * 2 capsules once daily for three days
  Other Name: Azithromycin
• Drug: Placebo
  Lactose powder

• Experimental: Azithromycin
  500 mg of azithromycin (2×250mg capsules)
  Intervention: Drug: Zithromax
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

Patients meeting all of the following criteria will be considered for admission to the study:

• Adults, either sex, ages 18-55 years or age 56 to 65 with < 20 pack year smoking history or age >65 with <5 pack year smoking history
• Patients with a documented history of asthma for >6 consecutive months, and
• Patients presenting within 24 hours (of initial presentation to medical care) with an acute deterioration in asthma control (increased wheeze, dyspnea and/or cough and/or reduced PEF) and requiring a course of oral steroids
• Patients with a PEF or FEV1 less than 80% of predicted normal or patient's best at presentation, at recruitment or in the time elapsed between presentation and recruitment
• Patients must be able to complete diaries and quality of life questionnaires.
• Patients must sign and date an informed consent prior to any study procedures.

Exclusion Criteria:

Patients presenting with any of the following will not be included in the study:

• Smokers aged 56-65 with a >20 pack year history
• Patients requiring immediate placement in ICU
• Patients who used oral or systemic antibiotics within 28 days prior to enrolment
• Patients with known impaired hepatic function (ALT/AST > 2 ULN)
• Patients with significant lung disease (including COPD) other than asthma
• Patients with ≥ 10mg oral corticosteroid maintenance therapy
• Patients requiring other antibiotic therapy
• Patients who are receiving other medications or who have other disease conditions or infections that could interfere with the evaluation of drug efficacy or safety
• Women who are breast-feeding or are pregnant, as demonstrated by a urine pregnancy test carried out before exposure to study medication or the start of any study procedure that could pose a risk to the foetus
• Patients with suspected or known hypersensitivity to, or suspected serious adverse reaction to Azithromycin or any of the macrolide or ketolide class of antibiotics, erythromycin or to any excipients thereof
• Patients who have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow up phase
• Patients with a concomitant condition (including clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic disease) making implementation of the protocol or interpretation of the study results difficult
• Patients with mental conditions rendering them unable to understand the nature, scope, and possible consequences of the study.
• Patients unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits.
• No subject will be allowed to enrol in this study more than once.