Condition category
Respiratory
Date applied
14/08/2017
Date assigned
23/08/2017
Last edited
23/08/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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. 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)

When is the study starting and how long is it expected to run for?
November 2012 to January 2020

Who is funding the study?
NIHR Trainees Co-ordinating Centre (UK)

Who is the main contact?
Hania Piotrowska

Trial website

Contact information

Type

Scientific

Primary contact

Miss Hania Piotrowska

ORCID ID

Contact details

University of Oxford
Respiratory Medicine
Old Road Campus
Roosevelt Drive
Oxford
OX3 7FZ
United Kingdom

Additional identifiers

EudraCT number

2017-001586-24

ClinicalTrials.gov number

Protocol/serial number

34829

Study information

Scientific title

Delivering personalised care in the management of exacerbations of chronic obstructive pulmonary disease: a multi-centre randomised clinical trial

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

London – Fulham Research Ethics Committee, 04/08/2017, ref: 17/LO/1135

Study design

Randomised; Interventional; Design type: Treatment, Drug, Management of Care

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

http://www.ndmrb.ox.ac.uk/respiratory-medicine-unit

Condition

Specialty: Respiratory disorders, Primary sub-specialty: Respiratory disorders; UKCRC code/ Disease: Respiratory/ Chronic lower respiratory diseases

Intervention

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

Phase

Phase IV

Drug names

Primary outcome measures

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 trial start date

01/11/2012

Overall trial end date

01/01/2020

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 228; UK Sample Size: 228

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

01/10/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Bicester Health Centre
The Health Centre Coker Close
Bicester
OX26 6AT

Trial participating centre

Broadshires Health Centre
Broadshire Way
Carterton
OX18 1JA

Trial participating centre

Montgomery House Surgery
Piggy Lane
Bicester
OX26 6HT

Trial participating centre

White Horse Medical Practice
Faringdon Medical Centre Volunteer Way
Faringdon
SN7 7YU

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials and Research Governance
University of Oxford
Oxford
OX3 7LE
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Trainees Co-ordinating Centre (TCC); Grant Codes: PDF-2013-06-052

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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 statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

01/01/2021

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes