Plain English Summary
Background and study aims
Chronic Obstructive Pulmonary Disease (COPD) is a lung disease that causes obstruction of the airflow. In the UK, it affects around 3 million people. It is the fifth leading cause of death and costs the NHS about £1 billion each year. Recommended treatment for COPD includes inhaled corticosteroids (ICS) to reduce worsening of symptoms and improve lung function. However, this is not very effective and even high doses fail to prevent worsening of the disease. Research shows that low dose theophylline may be effective, and when used with ICS will reduce worsening of the disease. In this study we will find out the clinical and cost effectiveness of adding low dose theophylline to ICS therapy in patients with COPD.
Who can participate?
We will recruit male and female patients aged 40 and over, who have COPD, who are taking inhaled corticosteroids and who have had two or more instances of worsening of symptoms in the previous year.
What does the study involve?
After they have agreed to take part, participants will be randomly allocated to receive either theophylline or placebo (dummy) for 12 months. We will follow up participants at six and 12 months to assess the number of occurrences of worsening of symptoms. We will also collect information on side effects, usage of the available health care, quality of life and breathlessness, and lung function.
What are the possible benefits and risks of participating?
Higher doses of theophylline have been used for more than 70 years to treat asthma and COPD. Side effects (such as anxiety, sleeplessness, dizziness, headache, rapid heart beat, upset stomach, rash, urine retention) can occur. It is estimated that at a low dose (as will be used in our study), less than 5% of participants will experience side effects. Participants who receive the theophylline may benefit as a result of receiving this drug because the risk of worsening may be less than without the drug. Participants who receive placebo may benefit because of evidence that participation in a clinical study improves the condition possibly due to better adherence to the background therapy.
Where is the study run from?
We will recruit participants from GP surgeries and hospitals across seven areas of the UK (Grampian, Glasgow, Newcastle, Hull, Liverpool, Birmingham and East Anglia).
When is the study starting and how long is it expected to run for?
Recruitment starts in September 2013 and is expected to be completed by August 2015. Follow-up within the study will be completed by September 2016. The study will report its findings in 2017.
Who is funding the study?
The study is funded by the National Institute for Health Research (NIHR), UK.
Who is the main contact?
The TWICS study office
Tel: +44 (0)1224 438178
Email: twics@abdn.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Seonaidh Cotton
ORCID ID
Contact details
Centre for Healthcare Randomised Trials (CHaRT)
Health Services Research Unit
3rd Floor
Health Sciences Building
Polwarth Building
Foresterhill
Aberdeen
AB25 2ZD
United Kingdom
-
s.c.cotton@abdn.ac.uk
Additional identifiers
EudraCT number
2013-001490-25
ClinicalTrials.gov number
Protocol/serial number
14832; HTA 11/58/15
Study information
Scientific title
A randomised, double-blind placebo controlled trial of the effectiveness of low dose oral Theophylline as an adjunct to Inhaled CorticoSteroids in preventing exacerbations of chronic obstructive pulmonary disease (COPD)
Acronym
TWICS
Study hypothesis
Preclinical and pilot studies demonstrate that low dose theophylline may increase the sensitivity of the airway inflammation to ICS, and thus when used with ICS will reduce the rate of COPD exacerbation. In this study we will determine the clinical effectiveness and cost-effectiveness of adding low dose theophylline to ICS therapy in patients with COPD. Low dose theophylline is cheap (10p/day) and, if shown to make current ICS therapy more effective in a cost effective manner, it will improve the quality of life of COPD patients and reduce the burden of COPD on the NHS.
More details can be found at http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=14832 and http://www.nets.nihr.ac.uk/projects/hta/115815
Protocol can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0004/81166/PRO-11-58-15.pdf
Ethics approval
Medical Research Ethic Committee (MREC), 28/06/2013, ref: 13/SS/0081
Study design
Randomised; Interventional; Design type: Prevention, Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Primary Care Research Network for England, Respiratory; Subtopic: Not Assigned, Respiratory (all Subtopics); Disease: Respiratory, All Diseases
Intervention
Participants will be randomised to theophylline (200 mg once or twice daily depending on smoking status and weight) or placebo for 12 months.
Intervention type
Drug
Phase
Not Applicable
Drug names
Theophylline
Primary outcome measures
Exacerbations of COPD necessitating change of management; Timepoint(s): 1 year treatment period
Secondary outcome measures
1. Adverse events; Timepoint(s): During 1 year treatment period
2. Cost per quality-adjusted life year (QALY); Timepoint(s): Cost per QALY during 1 year treatment period
3. Disease specific health status [(COPD Assessment Test (CATest)]; Timepoint(s): 6 months, 12 months
4. Emergency hospital admissions; Timepoint(s): During 1 year treatment period
5. EQ-5D (measure of health outcome); Timepoint(s): 6 months, 12 months
6. Exacerbations requiring hospital admission; Timepoint(s): during 1 year treatment period
7. Health care utilisation; Timepoint(s): during 1 year treatment period
8. Inhaled corticosteroid dose/useage; Timepoint(s): during 1 year treatment period
9. Lung function; Timepoint(s): 6 months, 12 months
10. Mortality; Timepoint(s): During 1 year treatment period
Overall trial start date
16/09/2013
Overall trial end date
01/09/2016
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged 40 years
2. A smoking history of at least 10 pack years
3. An established predominant respiratory diagnosis of COPD (post bronchodilator FEV1/FVC<0.7)
4. Current use of ICS therapy (irrespective of long-acting beta agonist (LABA) and/or long-acting anticholinergic agent (LAMA) use)
5. A history of at least two exacerbations requiring treatment with antibiotics and/or oral corticosteroid in the previous year, based on patient report
6. Clinically stable with no COPD exacerbation for at least 4 weeks
7. Able to swallow study medication
8. Able and willing to give informed consent to participate
9. Able and willing to participate in the study procedures, undergo spirometric assessment, complete study questionnaire
Target Gender: Male & Female; Lower Age Limit 40 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 1424; UK Sample Size: 1424
Participant exclusion criteria
1. Severe or unstable ischaemic heart disease
2. A predominant respiratory disease other than COPD
3. Any other significant disease/disorder which, in the investigators opinion, either puts the patient at risk because of study participation or may influence the results of the study or the patient's ability to participate in the study
4. Previous allocation of a randomisation code in the study or current participation in another interventional clinical study
5. Theophylline use currently
6. Known or suspected hypersensitivity to theophylline
7. Current use of drugs known to interact with theophylline and/or increase serum theophylline: antimicrobials: aciclovir, clarithromiycin, ciprofloxacin, erythromycin, fluconazole, ketoconazole, levofloxacin, norfloxacin; cardiovascular: diltiazem, mexiletine, pentoxifylline, verapamil;neurological: bupropion, disulfiram, fluvoxamine, lithium;hormonal: medroxyprogesterone, oestrogens; immunological: methotrexate, peginterferon alpha, tacrolimus; miscellaneous: cimetidine, deferasirox, febuxostat, roflumilast, thiabendazole
8. For women, current pregnancy or breast-feeding, or planned pregnancy during the study
Recruitment start date
16/09/2013
Recruitment end date
01/08/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Centre for Healthcare Randomised Trials (CHaRT)
Aberdeen
AB25 2ZD
United Kingdom
Funders
Funder type
Government
Funder name
National Institutes for Health Research (NIHR) (UK) - Health Technology Assessment; Grant Codes: 11/58/15
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26058585