Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis (VitalBE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03696290
Recruitment Status : Not yet recruiting
First Posted : October 4, 2018
Last Update Posted : October 10, 2019
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
University of Dundee

Brief 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.


Condition or disease Intervention/treatment Phase
Bronchiectasis Adult Drug: Aztreonam lysine Other: Placebo Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multi-centre randomised double-blind placebo controlled parallel group trial with four treatment arms
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Trail management team will also be masked. A bespoke online randomisation system will be used to generate the treatment codes for each participant
Primary Purpose: Treatment
Official Title: A Trial of the Safety, Tolerability and Efficacy of 2 Doses of Cayston (Aztreonam Lysine) Compared to Placebo in Participants With Bronchiectasis
Estimated Study Start Date : October 19, 2019
Estimated Primary Completion Date : October 31, 2020
Estimated Study Completion Date : October 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Aztreonam lysine, 3 doses per day
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
Nebulised aztreonam lysine 75mg
Other Name: Cayston

Placebo Comparator: Placebo, 3 doses per day
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
Nebulised lactose monohydrate 5mg
Other Name: Lactose monohydrate

Active Comparator: Aztreonam lysine, 2 doses per day
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
Nebulised aztreonam lysine 75mg
Other Name: Cayston

Placebo Comparator: Placebo, 2 doses per day
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
Nebulised lactose monohydrate 5mg
Other Name: Lactose monohydrate




Primary Outcome Measures :
  1. The number of adverse events, serious adverse events and trial treatment withdrawals in order to evaluate the safety and tolerability of Aztreonam lysine [ Time Frame: 12 months ]
    Adverse events, serious adverse events and trial treatment withdrawals will be recorded and a comparison made between the 4 treatment groups


Secondary Outcome Measures :
  1. To determine the effect of Aztreonam Lysine on time to first protocol-defined pulmonary exacerbation [ Time Frame: 12 months ]
    Time to first exacerbation, measured in days

  2. To determine the effect of Aztreonam lysine on the frequency of protocol-defined exacerbations over 12 months [ Time Frame: 12 months ]
    Number of exacerbation events

  3. To determine the effect of Aztreonam lysine on quality of life using the St Georges Respiratory questionnaire [ Time Frame: 12 months ]

    St. Georges Respiratory Questionnaire is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction.

    Scores are calculated for three domains:

    Symptoms, Activity and Impacts (Psycho-social) as well as a total score. The score correlates significantly with other measures of disease activity such as cough, dyspnoea, 6-min walk test and FEV1 as well as other measures of general health. http://www.healthstatus.sgul.ac.uk/sgrq


  4. To determine the effect of Aztreonam lysine on quality of life using the Quality of Life (QOL) Bronchiectasis Questionnaire [ Time Frame: 12 months ]

    QOL Bronchiectasis Questionnaire is a new, disease-specific health-related qualify of life (HRQOL) measure for adults with non-CF bronchiectasis. It has several different scales, including symptoms, physical, social and emotional functioning. It was developed using the FDA Guidance on Patient-Reported Outcomes1 beginning with interviews with health care providers, open-ended interviews with patients, item generation, cognitive testing and then a national psychometric validation. It is being used internationally in several clinical trials. It is also used clinically during routine clinic visits.

    Speight, J., & Barendse, S. M. (2010). FDA guidance on patient reported outcomes. BMJ, 340. The questionnaire measures functioning in a variety of domains, including Physical Functioning, Role Functioning, Vitality, Emotional Functioning, Social Functioning, Treatment Burden, Health Perceptions, and Respiratory Symptoms. High scores indicate better health-related quality of life.


  5. To determine the effect of Aztreonam lysine on quality of life using the Bronchiectasis Health Questionnaire [ Time Frame: 12 months ]

    The BHQ is a brief, valid and repeatable, self-completed health status questionnaire for bronchiectasis that generates a single total score. It can be used in the clinic to assess bronchiectasis from the patient's perspective.

    "The development and validation of the Bronchiectasis Health Questionnaire Arietta Spinou, Richard J. Siegert, Wei-jie Guan, Amit S. Patel, Harry R. Gosker, Kai K. Lee, Caroline Elston, Michael R. Loebinger, Robert Wilson, Rachel Garrod, Surinder S. Birring. European Respiratory Journal 2017 49: 1601532


  6. To determine the effect of Aztreonam lysine on pulmonary function [ Time Frame: 12 months ]
    Spirometry, specifically the forced expiratory volume in 1 minute

  7. Bacterial load at the end of the first treatment cycle [ Time Frame: 28 days ]
    Colony Forming Units per mililitre (CFU/ml)


Other Outcome Measures:
  1. To determine the impact of Aztreonam lysine on the time to first exacerbation, including all clinically treated exacerbations [ Time Frame: 12 months ]
    Time to first exacerbation (protocol defined and non-protocol defined)

  2. To determine the compliance with medication regimes [ Time Frame: 12 months ]
    Missed doses of medication will be counted for each treatment group



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03696290


Contacts
Layout table for location contacts
Contact: James Chalmers, MBChB, MRCP 01382 386131 j.chalmers@dundee.ac.uk
Contact: Clare Clarke, PhD 01382 383108 c.z.clarke@dundee.ac.uk

Locations
Layout table for location information
United Kingdom
NHS Tayside
Dundee, United Kingdom, DD1 9SY
Sponsors and Collaborators
University of Dundee
Gilead Sciences
Investigators
Layout table for investigator information
Principal Investigator: James Chalmers, MBChB, MRCP University of Dundee

Layout table for additonal information
Responsible Party: University of Dundee
ClinicalTrials.gov Identifier: NCT03696290     History of Changes
Other Study ID Numbers: 2016RC27
2018-001590-24 ( EudraCT Number )
First Posted: October 4, 2018    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University of Dundee:
Bronchiectasis
Additional relevant MeSH terms:
Layout table for MeSH terms
Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases
Aztreonam
Anti-Bacterial Agents
Anti-Infective Agents