AZithromycin Against pLacebo in Exacerbations of Asthma

A Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Oral Azithromycin (500 Mg OD) as a Supplement to Standard Care for Adult Patients With Acute Exacerbations of Asthma

Sponsors

Lead Sponsor: Imperial College London

Collaborator: National Institute for Health Research, United Kingdom

Source Imperial College London
Brief Summary

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.

Overall Status Completed
Start Date September 2011
Completion Date June 2014
Primary Completion Date June 2014
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Diary card summary symptom score 10 days after randomisation
Secondary Outcome
Measure Time Frame
Quality of life 5 & 10 days post randomisation
Time to 50% reduction in symptom score From Visit 1 (day 1) to Visit 4 (day 42)
Pulmonary Function tests 5 & 10 days post randomisation
Enrollment 199
Condition
Intervention

Intervention Type: Drug

Intervention Name: Zithromax

Description: 250mg * 2 capsules once daily for three days

Arm Group Label: Azithromycin (Zithromax)

Other Name: Azithromycin

Intervention Type: Drug

Intervention Name: Placebo

Description: Lactose powder

Arm Group Label: Placebo

Eligibility

Criteria:

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 >65 with <5 pack year smoking history

- Patients with a documented history of asthma for >6 consecutive months, and

- Patients presenting within 48 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:

- Patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure, patients on drugs known to prolong the QT interval and patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, aminodarone, sotalol) antiarrhythmic agents.

- Smokers aged 56-65 with a >20 pack year history, or aged >65 with >5 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 > 20mg 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Sebastian L Johnston, MBBS, PhD, FRCP Study Chair Imperial College London
Location
Facility:
Barnsley Hospital NHS Foundation | Barnsley, England, S75 2EP, United Kingdom
Countess of Chester Hospital NHS Foundation Trust | Liverpool, England, CH2 1UL, United Kingdom
Surrey & Sussex Healthcare NHS Trust | Surrey, England, RH1 5RH, United Kingdom
Heart of England NHS Foundation Trust | Birmingham, B9 5SS, United Kingdom
Blackpool Teaching Hospitals NHS Foundation Trust | Blackpool, FY3 8NR, United Kingdom
University of Glasgow | Glasgow, G12 0YN, United Kingdom
University Hospitals of Leicester NHS Foundation Trust | Leicester, LE39QP, United Kingdom
Imperial College Healthcare NHS Trust | London, W2 1PG, United Kingdom
University Hospital of South Manchester Foundation Trust | Manchester, M23 9QZ, United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle, NE7 7DN, United Kingdom
Nottingham University Hospitals NHS Trust | Nottingham, NG5 1PB, United Kingdom
Portsmouth Hospitals NHS Trust | Portsmouth, PO6 3LY, United Kingdom
University Hospital of North Tees | Stockton-on-Tees, TS19 8PE, United Kingdom
Sherwood Forest Hospitals NHS Foundation Trust | Sutton in Ashfield, NG17 4JL, United Kingdom
Location Countries

United Kingdom

Verification Date

November 2013

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Azithromycin (Zithromax)

Type: Experimental

Description: 500 mg of azithromycin (2×250mg capsules)

Label: Placebo

Type: Placebo Comparator

Description: Placebo

Acronym AZALEA
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov