AZithromycin Against pLacebo in Exacerbations of Asthma (AZALEA)

This study has been completed.
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01444469
First received: September 22, 2011
Last updated: July 22, 2014
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Zithromax
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Diary card summary symptom score [ Time Frame: 10 days after randomisation ] [ Designated as safety issue: Yes ]
    Symptoms include wheezing, breathlessness and coughing assessed at 10 days after randomisation.


Secondary Outcome Measures:
  • 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%


Enrollment: 199
Study Start Date: September 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azithromycin (Zithromax)
500 mg of azithromycin (2×250mg capsules)
Drug: Zithromax
250mg * 2 capsules once daily for three days
Other Name: Azithromycin
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Lactose powder

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01444469

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

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01444469     History of Changes
Other Study ID Numbers: 2011-001093-26, 10/60/27
Study First Received: September 22, 2011
Last Updated: July 22, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Asthma exacerbations
Respiratory disease
Viral infection
Macrolide/ketolide antibiotics
Mycoplasma pneumoniae (M. pneumoniae)
Chlamydophila pneumoniae (C. pneumoniae)

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014