Condition category
Respiratory
Date applied
13/03/2020
Date assigned
06/05/2020
Last edited
06/05/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Bronchiectasis is a long-term lung disease which is unrelated to smoking. People with bronchiectasis have ongoing phlegm production and repeated chest infections. A feature of bronchiectasis is a worsening in symptoms (known as an exacerbation) where patients have an increased cough, phlegm discolouration, excess phlegm production, breathlessness and/or tiredness. One of the main aims of bronchiectasis treatment is to reduce the number of exacerbations that patients experience. There has been little research carried out looking at the treatment of bronchiectasis even though there are over 300,000 patients with bronchiectasis in the UK.
To date, no treatments have been approved specifically for bronchiectasis. Instead, bronchiectasis treatments are based on treatments given for other lung conditions such as asthma or COPD (chronic obstructive pulmonary disorder) and there are differences in care. The main treatments used for bronchiectasis at the moment are drugs that make breathing easier by widening the airways (known as bronchodilators), inhaled steroids and long-term antibiotics. The main aim when treating bronchiectasis is to reduce exacerbations experienced by patients. Of these treatments only antibiotics have good proof of reducing exacerbations in bronchiectasis, however, proof for the other treatments is very limited. The aim of this study is to look at the use of bronchodilators and inhaled steroids in reducing exacerbations of bronchiectasis.

Who can participate?
Adult patients with bronchiectasis

What does the study involve?
The drugs being tested will be inhalers, there are three inhalers:
1. A dual bronchodilator inhaler
2. A dual bronchodilator combined with a corticosteroid inhaler
3. A placebo inhaler (a ‘dummy’ treatment)
Participants will stop taking any inhaler(s) they are already on, with the exception of their quick-acting inhaler (such as salbutamol). They will be randomly assigned to either one of the two treatment inhalers or the placebo inhaler (‘dummy’ treatment). They will have four times the chance of being on either one of the treatment inhalers as on the placebo inhaler. Participants and the trial doctor will not know which inhaler participants are allocated, all of the inhalers look identical. Participants will use the trial inhaler once a day for 12 months and will have four additional hospital visits over the 12 months. During these visits, participants will discuss their medical history, have some breathing tests and complete some questionnaires. They will have a telephone call every month to check that they have received their replacement inhaler through the post and will be asked to complete a diary each week for 12 months to record any bronchiectasis exacerbations they experience.

What are the possible benefits and risks of participating?
Participants cannot be assured that they will benefit directly from the taking part in the study, but the information gained may help to improve treatment for people with bronchiectasis in the future. The safety and side effects of these inhalers in other lung conditions are well known. It is possible that participants may experience side effects but these will be closely monitored, and if necessary the study doctor will be able to change their medication and put treatment in place to ease any symptoms. Participants allocated to the dummy treatment may find that they experience more exacerbations than on their current treatment.

Where is the study run from?
Newcastle University (UK)

When is the study starting and how long is it expected to run for?
October 2019 to August 2023

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Kassie Newell
dibs@newcastle.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Ms Kassie Newell

ORCID ID

Contact details

1-4 Claremont Terrace
Newcastle Upon Tyne
NE2 4AE
United Kingdom
+44 (0)191 208 2526
kassie.newell@newcastle.ac.uk

Type

Public

Additional contact

Dr Rachel Lakey

ORCID ID

Contact details

1-4 Claremont Terrace
Newcastle Upon Tyne
NE2 4AE
United Kingdom
+44 (0)191 208 5364
rachel.lakey@newcastle.ac.uk

Type

Public

Additional contact

Dr Miranda Morton

ORCID ID

Contact details

1-4 Claremont Terrace
Newcastle Upon Tyne
NE2 4AE
United Kingdom
+44 (0)191 208 2523
Miranda.Morton@newcastle.ac.uk

Additional identifiers

EudraCT number

2019-004466-17

ClinicalTrials.gov number

Nil known

Protocol/serial number

NIHR127460

Study information

Scientific title

A pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial, incorporating an internal pilot, to determine the role of bronchodilators in preventing exacerbations of bronchiectasis

Acronym

Dual Bronchodilators in Bronchiectasis Study (DIBS)

Study hypothesis

DIBS is a pragmatic multi-centre, placebo-controlled three-arm double-blind randomised controlled trial, incorporating an internal pilot. The aim of the trial is to determine whether treatment with either dual bronchodilators as a standalone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations experienced by bronchiectasis patients in a 12-month period.

Ethics approval

Submission pending

Study design

Pragmatic multi-centre placebo-controlled three-arm double-blind randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Bronchiectasis

Intervention

Participants will be randomised to one of the three trial groups in a 2:2:1 ratio to receive either dual therapy (LAMA/LABA), triple therapy (ICS/LAMA/LABA) or placebo:
1. Anoro Ellipta dry powder inhaler (LAMA/LABA - 55 micrograms umeclidinium and 22 micrograms vilanterol)
2. Trelegy Ellipta dry powder inhaler (ICS/LAMA/LABA - 92 micrograms fluticasone furoate, 55 micrograms umeclidinium and 22 micrograms vilanterol)
3. Placebo (matched placebo dry powder inhaler)

Participants will use the trial inhaler once a day for 12 months and will have four additional hospital visits over the 12 months. They will have a telephone call every month to check that they have received their replacement inhaler through the post and will be asked to complete an exacerbation diary each week for 12 months to record any bronchiectasis exacerbations.

Intervention type

Drug

Phase

Phase II

Drug names

Anoro Ellipta dry powder inhaler, Trelegy Ellipta dry powder inhaler

Primary outcome measure

Primary outcome measure:
Number of bronchiectasis exacerbations requiring treatment with antibiotics during 12 month treatment period as measured using participant reports and completed weekly exacerbation diary

Primary economic outcome measure:
1. Cost per QALY at 12 months: costs based on the cost of the interventions, use of health services via a Participant Cost questionnaire administered at 1, 6 and 12 months post-randomisation and adverse events
2. QALYs measured via the EQ-5D-5L at baseline, 1, 6 and 12 months post-randomisation

Secondary outcome measures

1. Number of hospital admissions for bronchiectasis exacerbations during 12 month treatment period, as measured using participant reports and completed weekly exacerbation diary and verified where possible by hospital discharge summary/HES data
2. Time to first exacerbation of bronchiectasis as measured using participant reports/completed weekly exacerbation diary
3. Number of emergency hospital admissions (all-cause) as ascertained from primary care records at 1, 6 and 12 months visits and where needed
4. Number of adverse events/drug reactions and cessation of treatment as reported by the participant to the research team or at 1, 6 and 12 months visits
5. Health status measured using SGRQ (St Georges Respiratory questionnaire) and bronchiectasis specific quality of life measured using QOL-B (quality of life - bronchiectasis) at baseline, 1, 6 and 12 months visits
6. Health-related quality of life measured using EQ-5D-5L at baseline, 1, 3, 6 and 12 months visits
7. Breathlessness measured using BDI (baseline dyspnoea index) at baseline
8. Breathlessness measured using TDI (transition dyspnea index) at 1, 6 and 12 months visits
9. Post bronchodilator lung function (LABA within 8 hours, short-acting beta2 agonist within 2 hours) as measured by spirometry performed to ATS/ERS standards at baseline, 1, 6 and 12 month visits:
9.1. Forced expiratory volume in 1 second (FEV1)
9.2. Forced vital capacity (FVC)
10. All-cause, respiratory and cardiac mortality measured using Office of National Statistics data at 12 months
11. Incremental cost per exacerbation avoided measured using Patient Cost Questionnaire at baseline, 1, 6 and 12 months
12. Costs to the NHS and patients and lifetime cost-effectiveness based on extrapolation modelling at 12 months
13. Rates of radiologically confirmed pneumonia, compared to participant’s normal baseline measured by asking participants at 1, 6 and 12 months

Exploratory measures:
Eosinophil count measured as the number of cells per microliter of blood and categorised as low - normal (0-150/mm3) and normal - high (>150/mm3) at baseline as both a single measure at that point and a median eosinophil level (median of last three available recordings when not on oral steroids)

Overall trial start date

01/10/2019

Overall trial end date

01/08/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adult patients with CT scan confirmed bronchiectasis and bronchiectasis is the predominant primary respiratory disease in the view of the investigator (CT images / CT reports must be available to complete radiological scoring for BSI)
2. History of 3 or more exacerbations in the preceding 12 months requiring antibiotics and/or steroids
3. Evidence of airflow limitation with an FEV1/FVC ratio less than 0.7 and/or daily mucus expectoration
4. Have less than 20 pack-year history of smoking
5. Willing to have baseline treatment altered / ICS etc. stopped if already taking
6. Stable for 4 weeks prior to baseline
7. Stable dose of oral steroid for 4 weeks prior to baseline (only applicable for patients taking oral steroid as part of standard care)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

600

Participant exclusion criteria

1. Cystic fibrosis related bronchiectasis
2. Where bronchiectasis is not the main disease or there are contraindications to ICS withdrawal
3. Predominant COPD or asthma (Patients who have a historical diagnosis of asthma and/or COPD but where the investigator has sufficient evidence to refute these diagnoses can still be included. This is to be documented in the source and the CRF)
4. Indication to remain on ICS (e.g. asthma, COPD, allergic bronchopulmonary aspergillosis, inflammatory bowel disease) or known intolerance to any of the trial drugs or their ingredients
5. Inability to perform spirometry or quality of life questionnaires
6. Patients who are:
6.1. Pregnant
6.2. Breastfeeding
6.3. Of childbearing potential with a positive urine pregnancy test prior to starting trial IMP
6.4. Male or female of childbearing potential unwilling to use contraception throughout the trial
(postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential).
7. Anyone with cognitive impairment who may not be able to consent
8. Those who do not speak English or cannot comply with trial procedures
9. Any potential participant who the investigator believes will not be able to complete the study visits and procedures
10. A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, β2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator contraindicates study participation
11. Use of acute antibiotics or systemic steroids within 4 weeks of baseline

Recruitment start date

01/08/2020

Recruitment end date

01/08/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Unknown as of yet
-
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne Hospitals NHS Foundation Trust

Sponsor details

Freeman Hospital
Freeman Road
Newcastle upon Tyne
NE7 7DN
United Kingdom
+44 (0)191 2825959
tnu-tr.sponsormanagement@nhs.net

Sponsor type

Hospital/treatment centre

Website

http://www.newcastle-hospitals.org.uk/

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

1. Protocol will be published on the NIHR HTA site and will be published as a protocol paper in a journal
2. Planned publication in a high-impact peer-reviewed journal

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from dibs@newcastle.ac.uk.

Intention to publish date

01/08/2024

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

04/05/2020: Trial's existence confirmed by the NIHR.