Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis

NCT03696290 | Terminated Phase 4 DMC FDA Drug

• 2 other identifiers: 2016RC272018-001590-24
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 14

Brief Summary

A randomised controlled trial of the safety, tolerability and effectiveness of Cayston 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.

Conditions

Bronchiectasis Adult

Keywords

Bronchiectasis

Outcome Measures

Primary Outcomes (1)

• The number of adverse events, serious adverse events and trial treatment withdrawals in order to evaluate the safety and tolerability of Aztreonam lysine

  Adverse events, serious adverse events and trial treatment withdrawals will be recorded and a comparison made between the 4 treatment groups

  12 months

Secondary Outcomes (7)

• To determine the effect of Aztreonam Lysine on time to first protocol-defined pulmonary exacerbation

  12 months

• To determine the effect of Aztreonam lysine on the frequency of protocol-defined exacerbations over 12 months

  12 months

• To determine the effect of Aztreonam lysine on quality of life using the St Georges Respiratory questionnaire

  12 months

• To determine the effect of Aztreonam lysine on quality of life using the Quality of Life (QOL) Bronchiectasis Questionnaire

  12 months

• To determine the effect of Aztreonam lysine on quality of life using the Bronchiectasis Health Questionnaire

  12 months

Other Outcomes (2)

• To determine the impact of Aztreonam lysine on the time to first exacerbation, including all clinically treated exacerbations

  12 months

• To determine the compliance with medication regimes

  12 months

Study Arms (4)

Aztreonam lysine, 3 doses per day

ACTIVE COMPARATOR

3 doses per day of nebulised Aztreonam lysine (75 mg) for 1 month, followed by 1 month off treatment. The month on, month off regimen will be repeated for a total peroid of 12 months.

Drug: Aztreonam lysine

Placebo, 3 doses per day

PLACEBO COMPARATOR

3 doses per day of nebulised placebo (5 mg lactose monohydrate) for 1 month, followed by 1 month off treatment. The month on, month off regimen will be repeated for a total peroid of 12 months.

Other: Placebo

Aztreonam lysine, 2 doses per day

ACTIVE COMPARATOR

2 doses per day of nebulised Aztreonam lysine (75 mg) for 1 month, followed by 1 month off treatment. The month on, month off regimen will be repeated for a total peroid of 12 months.

Drug: Aztreonam lysine

Placebo, 2 doses per day

PLACEBO COMPARATOR

2 doses per day of nebulised placebo (5 mg lactose monohydrate) for 1 month, followed by 1 month off treatment. The month on, month off regimen will be repeated for a total peroid of 12 months.

Other: Placebo

Interventions

Aztreonam lysine DRUG

Nebulised aztreonam lysine 75mg

Also known as: Cayston

Aztreonam lysine, 2 doses per day; Aztreonam lysine, 3 doses per day

Placebo OTHER

Nebulised lactose monohydrate 5mg

Also known as: Lactose monohydrate

Placebo, 2 doses per day; Placebo, 3 doses per day

Eligibility Criteria

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

You may qualify if:

• ≥ 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: collaborator
• University of Dundee: lead

Study Sites (14)

Torbay Hospital

Torquay, Devon, TQ2 7AA, United Kingdom

Location

Royal Papworth hospital NHS Foundation Trust

Cambridge, CB2 0AY, United Kingdom

Location

Cardiff & Vale University Local Health Board

Cardiff, CF14 4HH, United Kingdom

Location

University Hospitals of Derby and Burton NHS Foundation Trust

Derby, United Kingdom

Location

NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

NHS Lanakrshire University Hospital Hairmyres

East Kilbride, G75 8RG, United Kingdom

Location

The Princess Alexandra Hospital NHS Trust

Harlow, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, L14 3PE, United Kingdom

Location

Aintree University Hospital

Liverpool, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust

London, United Kingdom

Location

Manchester University NHS Foundation Trust - Wythenshawe Hospital

Manchester, M13 9WL, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

University hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

NHS Lanarkshire: University Hospital Wishaw

Wishaw, ML2 0DP, United Kingdom

Location

MeSH Terms

Conditions

Bronchiectasis

Interventions

Aztreonam

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• James Chalmers, MBChB, MRCP

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Trail management team will also be masked. A bespoke online randomisation system will be used to generate the treatment codes for each participant
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Multi-centre randomised double-blind placebo controlled parallel group trial with four treatment arms

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: October 4, 2018
• Study Start: October 19, 2019
• Primary Completion: November 26, 2024
• Study Completion: March 4, 2025
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (14)