AZithromycin Against pLacebo in Exacerbations of Asthma

NCT ID: NCT01444469

Last Updated: 2024-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 199 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2014-06-30

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Azithromycin (Zithromax)

500 mg of azithromycin (2×250mg capsules)

Group Type: EXPERIMENTAL

Zithromax

Intervention Type: DRUG

250mg \* 2 capsules once daily for three days

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Lactose powder

Interventions

Zithromax

250mg \* 2 capsules once daily for three days

Intervention Type: DRUG

Placebo

Lactose powder

Intervention Type: DRUG

Other Intervention Names

Azithromycin

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sebastian L Johnston, MBBS, PhD, FRCP

Role: STUDY_CHAIR

Imperial College London

Locations

Barnsley Hospital NHS Foundation

Barnsley, England, United Kingdom

Countess of Chester Hospital NHS Foundation Trust

Liverpool, England, United Kingdom

Surrey & Sussex Healthcare NHS Trust

Redhill, England, United Kingdom

Heart of England NHS Foundation Trust

Birmingham, , United Kingdom

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, , United Kingdom

University of Glasgow

Glasgow, , United Kingdom

University Hospitals of Leicester NHS Foundation Trust

Leicester, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

University Hospital of South Manchester Foundation Trust

Manchester, , United Kingdom

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Portsmouth Hospitals NHS Trust

Portsmouth, , United Kingdom

University Hospital of North Tees

Stockton-on-Tees, , United Kingdom

Sherwood Forest Hospitals NHS Foundation Trust

Sutton in Ashfield, , United Kingdom

Countries

United Kingdom

References

Johnston SL, Szigeti M, Cross M, Brightling C, Chaudhuri R, Harrison T, Mansur A, Robison L, Sattar Z, Jackson D, Mallia P, Wong E, Corrigan C, Higgins B, Ind P, Singh D, Thomson NC, Ashby D, Chauhan A; AZALEA Trial Team. Azithromycin for Acute Exacerbations of Asthma : The AZALEA Randomized Clinical Trial. JAMA Intern Med. 2016 Nov 1;176(11):1630-1637. doi: 10.1001/jamainternmed.2016.5664.

Reference Type: DERIVED

PMID: 27653939 (View on PubMed)

Other Identifiers

10/60/27

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2011-001093-26

Identifier Type: -

Identifier Source: org_study_id