Azithromycin in Patients With CF, Infected With Burkholderia Cepacia Complex

NCT00298922 | Unknown Phase 2 DMC

• 2 other identifiers: AZ 0003TULLIS04A0
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary infection with Burkholderia cepacia complex (BCC) in patients with CF is often associated with a more rapid decline in lung function. Because of the resistance of BCC to many antibiotics, treatment options are often limited. New therapies to improve outcomes for patients infected with BCC are needed. However, because of the unpredictable nature of this pulmonary infection in CF, patients with BCC infection have been excluded from many CF therapeutic trials. Recent published trials in the United States, Australia, and the United Kingdom have all demonstrated clinical benefits from prolonged administration of azithromycin in CF. In these trials, the vast majority of patients were chronically infected with Pseudomonas aeruginosa. Patients with BCC were excluded from the US and UK trials, and only four patients with BCC infection were enrolled in the Australian trial. Thus, the effectiveness of azithromycin in CF patients infected with BCC is largely unknown and deserves further study. The two main ways by which azithromycin is thought to help with the chronic lung infections seen in CF are by \[a\] reducing inflammation and \[b\] direct effects on the bacteria, in particular P. aeruginosa. BCC pulmonary infection in CF is often associated with a large inflammatory response similar to or more severe than P. aeruginosa infection. If azithromycin works mainly by an anti-inflammatory mechanism, it should also be helpful in CF patients infected with BCC. Alternatively, azithromycin could have a direct effect on BCC as seen with P. aeruginosa as the two bacteria have many similarities.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Burkholderia cepacia complex

Outcome Measures

Primary Outcomes (1)

• Change in FEV1 in % predicted in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo.

  24 weeks

Study Arms (2)

Azithromycin

ACTIVE COMPARATOR

participants taking 500 mg tablets orally thrice weekly for 24 weeks

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

Participants taking 500 mg tablets orally thrice weekly for 24 weeks

Drug: Placebo

Interventions

Azithromycin DRUG

500 mg tablets orally thrice weekly for 24 weeks

Azithromycin

Placebo DRUG

tablet orally thrice weekly for 24 weeks

Placebo

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent and verbal assent as appropriate has been provided by the subject
• Ability to comply with medication use, study visits and study procedures as judged by the site Investigator
• Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
• \> 18 years of age
• Body weight \> 40 kg
• BCC present in a sputum/throat culture \> 1 year prior to screening and at screening
• FEV1 % predicted \> 30% as calculated by the Knudsen reference equations
• Room air oximetry \> 88% at rest
• Post-menarche females must be surgically sterile or using an effective form of contraception
• Predicted to live \> 1 year and clinically stable at that time of enrollment as judged by the investigator.

You may not qualify if:

• History of chronic macrolide use, defined as regular macrolide antibiotic use within a three month period prior to enrollment in the study.
• AST or ALT \> 2.5 times the upper limit of normal performed at the local laboratories on two occasions prior to randomization.
• Investigational drug use within 30 days of screening
• History of alcohol, illicit drug or medication abuse within 1 year of screening
• Use of intravenous antibiotics or oral antibiotics within 14 days of screening.
• Use of low dose oral antibiotics (e.g. macrolides, tetracycline, sulfa) for acne or other conditions within 30 days of screening
• Use of systemic corticosteroids (\> 20 mg of prednisone per day) within 30 days of screening
• Initiation of TOBI®, high dose ibuprofen, or rhDNase within 60 days of screening
• History of lung transplantation or currently on lung transplant list
• History of allergy to a macrolide antibiotic
• AFB smear positive at screening suggesting current NTM infection.
• Positive serum pregnancy test at screening (to be performed on all post-menarche females)
• Absolute neutrophil count \< 1000 performed at the local laboratories on two occasions prior to randomization
• Creatinine \> 1.5 times normal performed at the local laboratories on two occasions prior to randomization.
• Chest x-ray changes or physical findings at screening that would compromise the safety of the patient or the quality of the study data

Sponsors & Collaborators

• Unity Health Toronto: lead
• Cystic Fibrosis Foundation: collaborator
• Pfizer: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Elizabeth Tullis, MD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 2, 2006
• First Posted: March 3, 2006
• Study Start: February 1, 2006
• Primary Completion: February 1, 2009
• Study Completion: October 1, 2009
• Last Updated: July 31, 2009

Record last verified: 2009-07

Locations

CA (1)