Studying acute exacerbations and response: the COPD STARR 2 study
| ISRCTN | ISRCTN27510582 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN27510582 |
| EudraCT/CTIS number | 2017-001586-24 |
| ClinicalTrials.gov number | NCT04458636 |
| Secondary identifying numbers | 34829 |
- Submission date
- 14/08/2017
- Registration date
- 23/08/2017
- Last edited
- 02/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Chronic obstructive pulmonary disease (COPD) affects adults and is largely caused by smoking cigarettes. It is predicted to be the 3rd leading cause of death by 2020 affecting over 250 million people worldwide. COPD makes breathing increasingly difficult, with frequent periods of worsening symptoms. These are termed exacerbations and current treatment strategies rely on oral corticosteroids (prednisolone) and antibiotics but this is in a "one size fits all" approach. There is little evidence supporting this strategy and both treatments can potentially cause harm. In addition to this, previous findings have shown that eosinophil (white blood cell) counts within blood samples from COPD patients can be used as a marker to determine treatment with oral steroids. The aim of this study is to find out whether personalising treatment based on eosinophil counts is superior to current standard treatment strategies.
Who can participate?
Patients aged 40 or over with COPD
What does the study involve?
A participant's involvement lasts up to 12 months and involves up to 5 visits. These visits involve completing questionnaires, undergoing breathing tests, and giving urine and blood samples. Participants take the study drugs for 14 days during an exacerbation, when they are randomly allocated to one of two groups. One group receives antibiotics and either prednisolone or placebo depending on their blood eosinophil count. The other group receives prednisolone and antibiotics regardless of their blood eosinophil count. Participants are followed up at days 14, 30, 90 with a medical review of notes at 12 months. Participants may be re-randomised and followed up if they have further exacerbations after the 30 day visit. The number of participants who need more treatment, hospitalisation or die is assessed.
What are the possible benefits and risks of participating?
Participants receive no direct benefit from being involved in the study. However, the information from this study may be used to improve the treatment of people with COPD in the future. The breathing tests may cause coughing, chest tightness and occasional wheezing. The blood samples may cause some mild discomfort but this is expected to stop very quickly. Antibiotics can cause side effects such as stomach upset or rash. On very rare occasions, the participant may be allergic to prednisolone, antibiotics or the placebo.
Where is the study run from?
1. Bicester Health Centre (UK)
2. Broadshires Health Centre (UK)
3. Montgomery House Surgery (UK)
4. White Horse Medical Practice (UK)
5. Eynsham Medical Centre (UK)
6. Windrush Medical Practice (UK)
7. Gladstone Surgery (UK)
8. Alchester Medical Group (UK)
9. Woodlands Medical Centre (UK)
10. Haddenham Medical Centre (UK)
11. Morland House Surgery (UK)
12. Norden House (UK)
13. Swan Practice (UK)
14. Whitchurch Surgery (UK)
When is the study starting and how long is it expected to run for?
November 2012 to October 2020
Who is funding the study?
NIHR Trainees Co-ordinating Centre (UK)
Who is the main contact?
Professor Mona Bafadhel, mona.bafadhel@ndm.ox.ac.uk
Contact information
Public
Oxford Respiratory Trials Unit
University of Oxford
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
| Phone | +44 (0)1865 227612 |
|---|---|
| ortu@ndm.ox.ac.uk |
Scientific
Respiratory Medicine
John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom
| mona.bafadhel@ndm.ox.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug, Management of Care |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | http://www.ndmrb.ox.ac.uk/respiratory-medicine-unit |
| Scientific title | Delivering personalised care in the management of exacerbations of chronic obstructive pulmonary disease: a multi-centre randomised clinical trial |
| Study acronym | COPD STARR 2 |
| Study hypothesis | Chronic obstructive pulmonary disease (COPD) affects adults and is largely caused by cigarette smoke in the developed world. It is predicted to be the 3rd leading cause of death by 2020 affecting over 250 million people worldwide. COPD is characterised by progressive airflow obstruction punctuated by frequent periods of worsening in respiratory symptoms and function associated with a significant impact on quality of life. These episodes are termed exacerbations and current treatment strategies rely on oral corticosteroids (prednisolone) and antibiotics but this is in a "one size fits all" approach. However, there is little evidence supporting this strategy and both treatments can potentially cause harm. In addition to this, previous findings have shown that eosinophil counts within blood samples from COPD patients can be used as a biomarker to determine treatment with oral steroids. The study hypothesis is that personalising this treatment approach during an exacerbation of COPD, to direct whether corticosteroids is necessary for all patients, depending on the results of the eosinophil count from near-patient testing, is superior to current standard treatment strategies in the primary care setting. |
| Ethics approval(s) | London – Fulham Research Ethics Committee, 04/08/2017, ref: 17/LO/1135 |
| Condition | Chronic obstructive pulmonary disease |
| Intervention | Current interventions as of 29/01/2020 STARR 2 will be recruiting 228 participants with COPD from GP surgeries within the Thames Valley and South Midlands. A participant's involvement will last up until 12 months and will involve up to 5 visits. These visits will consist of CRF completion, questionnaires, breathing tests, urine testing, blood samples and spirometry. Participants will only be taking the trial drugs for 14 days during an exacerbation. Consented participants will be randomised (1:1) to standard or directed therapy using the centralised computer randomisation service RRAMP (https://rramp.octru.ox.ac.uk) provided by the Oxford Clinical Trials Research Unit (OCTRU). Randomisation will be undertaken using stratification to ensure a balanced allocation across treatment groups, stratified by eosinophil count, disease severity as measured by FEV at baseline and prior exacerbation history. As patients with COPD commonly experience on average two exacerbations per year, participants can be re-randomised if they experience a further exacerbation which meets the eligibility criteria and they consent to continue. This re-randomisation can occur in participants who have completed the study (attended a Day 90 visit), or participants who have completed a Day 30 visit. A maximum of 4 exacerbations per participant can be randomised to the study arms. All participants will be blinded to prednisolone therapy and receive open-labelled antibiotics ( doxycycline 100mg once per day for 7 days). Participants in the ‘blood eosinophil directed’ study arm will receive antibiotic (doxycycline, open labelled) and IMP (prednisolone or placebo) dependent on the blood eosinophil count at the randomisation (exacerbation visit). Participants in the ‘standard therapy’ study arm will receive IMP (prednisolone) and antibiotic (doxycycline, open labelled) irrespective of the blood eosinophil count at randomisation. Prednisolone therapy consists of prednisolone 30mg tablet taken orally per day for 14 days. Participants are followed up at days 14, 30, 90 with a medical review of notes at 12 months. Previous interventions STARR 2 will be recruiting 228 participants with COPD from GP surgeries within the Thames Valley and South Midlands. A participant's involvement will last up until 12 months and will involve up to 5 visits. These visits will consist of CRF completion, questionnaires, breathing tests, urine testing, blood samples and spirometry. Participants will only be taking the trial drugs for 14 days during an exacerbation. Consented participants will be randomised (1:1) to standard or directed therapy using the centralised computer randomisation service RRAMP (https://rramp.octru.ox.ac.uk) provided by the Oxford Clinical Trials Research Unit (OCTRU). Randomisation will be undertaken using stratification to ensure a balanced allocation across treatment groups, stratified by eosinophil count, disease severity as measured by FEV at baseline and prior exacerbation history. All participants will be blinded to prednisolone therapy and receive open-labelled antibiotics (doxycycline 100mg once per day for 7 days). Participants in the ‘blood eosinophil directed’ study arm will receive antibiotic (doxycycline, open labelled) and IMP (prednisolone or placebo) dependent on the blood eosinophil count at the randomisation (exacerbation visit). Participants in the ‘standard therapy’ study arm will receive IMP (prednisolone) and antibiotic (doxycycline, open labelled) irrespective of the blood eosinophil count at randomisation. Prednisolone therapy consists of prednisolone 30mg tablet taken orally per day for 14 days. Participants are followed up at days 14, 30, 90 with a medical review of notes at 12 months. |
| Intervention type | Other |
| Primary outcome measure | Efficacy of blood-eosinophil directed corticosteroid therapy compared to standard care measured by looking at the frequency of participants needing re-treatment, hospitalisation, death at 30 and 90 days |
| Secondary outcome measures | Measured at baseline, day 14, 30 and 90: 1. Quality of life, measured using CAT and EQ-5D 2. Symptoms, measured using VAS 3. Lung function, measured using FEV1 3. Healthcare utilisation, measured using exacerbation frequency in 12 months Exploratory outcome measures: 1. Stability of blood eosinophils, measured by the change in blood eosinophil counts at all visits (except 12 months) 2. Stability of mediatory levels in the blood, measured by looking at the change in inflammatory mediators during a stable state and at exacerbation |
| Overall study start date | 01/11/2012 |
| Overall study end date | 09/10/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 228; UK Sample Size: 228 |
| Total final enrolment | 308 |
| Participant inclusion criteria | 1. Participant is willing and able to give informed consent for participation in the trial 2. Male or female, aged 40 years or above 3. Diagnosed with COPD (primary or secondary care diagnosis) with spirometric confirmation of airflow obstruction (FEV1/FVC ratio <0.7) 4. A history of at least 1 exacerbation in the previous 12 months, requiring systemic corticosteroids and/or antibiotics 5. Current or ex-smoker with at least a 10 pack year smoking history 6. In the opinion of the research staff, is able and willing to comply with all trial requirements |
| Participant exclusion criteria | 1. History of atopic childhood asthma 2. Current history of primary lung malignancy or current active pulmonary TB 3. Clinically relevant disease or disorder (past or present) which in the opinion of the investigator may either put the subject at risk because of participating in the study or may influence the results of the study or the subject’s ability to participate in the study 4. Any clinically relevant lung disease, other than COPD considered by the investigator to be the primary diagnosis. For example mild-to-moderate bronchiectasis is acceptable in addition to COPD unless the bronchiectasis is considered to be the primary diagnosis 5. An alternative cause for the increase in symptoms of COPD that are unrelated to an exacerbation such as: 5.1. Suspicion or clinical evidence of pneumonia 5.2. High probability and suspicion of pulmonary embolism 5.3. Suspicion or clinical evidence of a pneumothorax 5.4. Primary ischaemic event – ST or Non ST elevation myocardial infarct and left ventricular failure [i.e. not an exacerbation of COPD] 6. A known allergy to the IMP (prednisolone), NIMP (doxycycline) or to any of the constituents of the placebo 7. Patients on maintenance corticosteroids (prednisolone, hydrocortisone, fludrocortisone) 8. Known adrenal insufficiency 9. Currently enrolled in another CTIMP trial and receiving an intervention as part of the trial 10. Pregnant and breastfeeding women |
| Recruitment start date | 18/09/2017 |
| Recruitment end date | 31/12/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Coker Close
Bicester
OX26 6AT
United Kingdom
Carterton
OX18 1JA
United Kingdom
Bicester
OX26 6HT
United Kingdom
Volunteer Way
Faringdon
SN7 7YU
United Kingdom
Eynsham
Witney
OX29 4QB
United Kingdom
Oxfordshire
Whitney
OX28 6JS
United Kingdom
260-290 Berkhampstead Rd
Chesham
HP5 3EZ
United Kingdom
Bicester
OX26 6XX
United Kingdom
Didcot
OX11 0BB
United Kingdom
Haddenham
Aylesbury
HP17 8JX
United Kingdom
Wheatley
Oxford
OX33 1YJ
United Kingdom
Winslow
Buckingham
MK18 3DW
United Kingdom
High Street
Buckingham
MK18 1NU
United Kingdom
Whitchurch
Aylesbury
HP22 4JF
United Kingdom
Sponsor information
University/education
Clinical Trials and Research Governance
University of Oxford
Oxford
OX3 7LE
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | The final results of the study will be submitted for publication and dissemination within one year after the trial overall end date in peer-reviewed scientific journals. Public dissemination of the study results will be via patient led organisations such as the British Lung Foundation and the Breathe Easy groups. |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version V6.0 | 08/04/2019 | 02/12/2020 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN27510582_PROTOCOL_V6.0_08Apr19.pdf
- Uploaded 02/12/2020
Editorial Notes
02/11/2022: The following changes have been made:
1. The public contact has been changed.
2. The NCT number has been added.
12/08/2021: The following changes were made to the trial record:
1. The intention to publish date was changed from 01/01/2021 to 31/12/2021.
2. The contact email was updated.
02/12/2020: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/12/2020 to 09/10/2020.
2. Total final enrolment added.
3. Uploaded protocol Version V6.0, 08 April 2019 (not peer reviewed).
29/01/2020: The following changes have been made:
1. The interventions have been updated.
2. The trial participating centre Eynsham Medical Centre has been added.
3. The trial participating centre Windrush Medical Practice has been added.
4. The trial participating centre Gladstone Surgery has been added.
5. The trial participating centre Alchester Medical Group has been added.
6. The trial participating centre Woodlands Medical Centre has been added.
7. The trial participating centre Haddenham Medical Centre has been added.
8. The trial participating centre Morland House Surgery has been added.
9. The trial participating centre Norden House Surgery has been added.
10. The trial participating centre The Swan Practice has been added.
11. The trial participating centre Whitchurch Surgery has been added.
12. The plain English summary has been updated to reflect the changes above.
14/01/2020: The overall trial end date has been changed from 01/01/2020 to 31/12/2020.
04/11/2019: The following changes have been made:
1. The public contact has been changed and the scientific contact added. The plain English summary has been updated accordingly.
2. The recruitment end date has been changed from 01/10/2019 to 31/12/2019.
03/04/2019: The condition has been changed from "Specialty: Respiratory disorders, Primary sub-specialty: Respiratory disorders; UKCRC code/ Disease: Respiratory/ Chronic lower respiratory diseases" to "Chronic obstructive pulmonary disease" following a request from the NIHR.
