Bronchiectasis Respiratory
Conditions
Interventions
Participants will be randomised using the online Tayside Randomisation System (TRuST) to one of the trial arms:
Arm 1: Usual care
Arm 2: Disulfiram 200 mg, two tablets taken orally, once daily
Arm 3:
Sponsors
University of Dundee
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Inclusion criteria
Inclusion criteria: 1. =18 years 2. Able to provide informed consent. 3. Capable of complying with all trial procedures and of completing the trial, in the opinion of the investigator. 4. Bronchiectasis, confirmed by computed tomography (CT), showing bronchiectasis in 1 or more lobes. 5. Normally produces sputum daily. 6. Able to provide a sputum sample at the screening visit or between screening and randomisation. 7. Active neutrophilic inflammation at screening/baseline indicated by a positive NEATstik (Neutrophil Elastase Airways Test) result.
Exclusion criteria
Exclusion criteria: 1. Enrolled previously in the trial 3 times. 2. Respiratory infection or bronchiectasis exacerbation 4 weeks prior to screening and/or between screening and randomisation 3. Antibiotic or corticosteroid 4 weeks prior to screening and/or between screening and randomisation 4. Active allergic bronchopulmonary aspergillosis (defined by International Society for Human and Animal Mycology criteria) on steroids and/or anti-fungals, 5. Nontuberculous mycobacterial infection on antibiotic therapy 6. Immunodeficiency on immunoglobulin replacement 7. A primary diagnosis of COPD or asthma (a secondary diagnosis of COPD or asthma is permitted) 8. Cystic fibrosis 9. Active malignancy except non-melanoma skin cancer 10. Currently taking brensocatib 11. Use of any investigational drugs within five times of the elimination half-life after the last dose or within 30 days, whichever is longer. Current enrolment in non-interventional, observational studies will be allowed 12. Currently pregnant or breast-feeding 13. Women of childbearing age and not practicing an acceptable method of birth control 14. Additional exclusion criteria for individual treatment arms are described in the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Activity of sputum Neutrophil elastase. Day 0 and 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 06/11/2024: 1. Activity of sputum Neutrophil elastase. Days 0, 7, 14 and 56 2. Time to first pulmonary exacerbation (EMBARC definition). Days 0 to 28 3. Quality of life-bronchiectasis (QOL-B) respiratory symptom scale, Bronchiectasis Impact Measure (BIM) questionnaire. Days 0, 7, 14, 28 and 56 4. Distance covered during a 6-minute walk. Days 0 to 28 5. Frequency of adverse events (AEs) and serious adverse events (SAEs). Day 0, 28 6. Phagocytosis of bacteria; Reactive oxygen species generation; Degranulation; Ex-vivo formation of neutrophil extracellular traps; Mass cytometry (endpoints may vary depending on the experimental arm). Days 0 to 56 Tertiary outcome measures: 1. Frequency of pulmonary exacerbations (EMBARC definition). Days 0 to 28; Days 0 to 56 2. Measure the concentration of MMPs and NETs in sputum, as well as other biomarkers e.g. proteomics, bacterial load, microbiome. Days 0, 7, 14, 28 and 56 3. Measure serum biomarkers of inflammation and redox status. Days 0, 7, 14, 28 and 56 4. Peripheral blood neutrophil proteomics performed on isolated cells. Days 0 and 28 Previous secondary outcome measures: 1. Activity of sputum Neutrophil elastase. Days 0, 7, 14 and 56 2. Time to first pulmonary exacerbation (EMBARC definition). Days 0 to 28 3. Quality of life-bronchiectasis (QOL-B) respiratory symptom scale, Bronchiectasis Impact Measure (BIM) questionnaire. Days 0, 7, 14, 28 and 56 4. Distance covered during a 6-minute walk. Days 0 to 28 5. Frequency of adverse events (AEs) and serious adverse events (SAEs). Day 0, 28 6. Phagocytosis of bacteria; Reactive oxygen species generation; Degranulation; Ex-vivo formation of neutrophil extracellular traps; Mass cytometry (endpoints may vary depending on the experimental arm). Days 0 to 56 Tertiary outcome measures: 1. Frequency of pulmonary exacerbations (EMBARC definition). Days 0 to 28; Days 0 to 56 2. Measure the concentration of MMPs and NETs in sputum, as well as ot | — |
Countries
England, Northern Ireland, Scotland, United Kingdom
Contacts
Public Contact. Study Team
Outcome results
None listed