Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis

• Status: Active, not recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

Summary

A randomised controlled trial of the safety, tolerability and effectiveness of 2 doses of Cayston (Aztreonam Lysine) compared to placebo in participants with bronchiectasis.

Bronchiectasis not due to cystic fibrosis is a chronic inflammatory disease characterised by cough, sputum production and frequent respiratory tract infections. There are currently no licensed therapies for bronchiectasis approved by regulators in the United States or Europe. The disease has a high morbidity, particularly in the presence of chronic P. aeruginosa and other chronic Gram-negative infections.

This trial will test the hypothesis that 12 months treatment with Aztreonam lysine for inhalation will be safe and well tolerated, and will result in a significant increase in the time to first pulmonary exacerbation in participants with bronchiectasis and a history of frequent exacerbations.

This is a multi-centre randomised double-blind placebo controlled parallel group trial with four treatment arms. It will enroll 100 bronchiectasis patients with a history of at least 3 exacerbations in the previous year and the presence of chronic Gram-negative infection in sputum at screening. Patients will be treated following a one month on, one month off treatment regimen for 12 months.

The primary objective is to evaluate the safety and tolerability of Aztrenam lysine in these patients by recording adverse events and trial treatment withdrawals.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Dundee
• Collaborator: Gilead Sciences
• Treatments: Aztreonam

Criteria

Inclusion Criteria:

• ≥ 18 years of age

• Able to give informed consent

• Clinical diagnosis of Bronchiectasis

• CT scan of the chest demonstrating bronchiectasis in 1 or more lobes

• A history of at least 3 exacerbations in the previous 12 months

• Bronchiectasis severity index score >4

• Pseudomonas aeruginosa or other Gram-negative respiratory pathogen detected in sputum or bronchoalveolar lavage on at least 1 occasion in the previous 12 months.

• A sputum sample that is culture positive for P. aeruginosa or other Gram-negative respiratory pathogens sent at the screening visit and within 28 days of randomization. Pre-specified eligible organisms include Eschericia coli, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Achromobacter, Enterobacter and Stenotrophomonas maltophilia

Exclusion Criteria:

• Participant has cystic fibrosis

• Immunodeficiency requiring replacement immunoglobulin.

• Active tuberculosis or nontuberculous mycobacterial infection (defined as currently under treatment, or requiring treatment in the opinion of the investigator).

• Recent significant haemoptysis (a volume requiring clinical intervention, within the previous 4 weeks).

• Treatment with inhaled, systemic or nebulized anti-Pseudomonal antibiotics in the 28 days prior to randomization

• Oral macrolides which have been taken for a period of less than 3 months prior to the start of the trial.

• Treatment of an exacerbation and receiving antibiotic treatment within 4 weeks of randomization

• Primary diagnosis of COPD associated with >20 pack years smoking history.

• History of poorly controlled asthma or a history of bronchospasm with inhaled antibiotics.

• Pregnant or lactating females.

• Participants with FEV1 <30% predicted value at screening.

• Previous history of intolerance to Aztreonam or bronchospasm reported with any other inhaled anti-bacterial.

• Glomerular filtration rate (eGFR) below 30ml/min/1.73m2 or requiring dialysis. This will be determined at screening.

• Use of any investigational drugs within five times of the elimination half-life after the last trial dose or within 30 days, whichever is longer.

• Unstable co-morbidities (cardiovascular disease, active malignancy) which in the opinion of the investigator would make participation in the trial not in the participants best interest.

• Long term oxygen therapy

• Women of child bearing age or male partners of women of child bearing age and not practicing a method of acceptable birth control (see below)