Effectiveness of electronic cigarettes compared with combination nicotine replacement therapy for smoking cessation in patients with chronic obstructive pulmonary disease and effect on lung health (ECAL Trial)
| ISRCTN | ISRCTN82413824 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82413824 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 1006828 |
| Protocol serial number | RG_20-120, CPMS 56604 |
| Sponsor | University of Birmingham |
| Funder | National Institute for Health and Care Research |
- Submission date
- 03/05/2023
- Registration date
- 04/10/2023
- Last edited
- 07/01/2026
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Chronic obstructive pulmonary disease (COPD) is a common lung condition which mainly affects adults aged 35 years and older, and it is most often caused by smoking. COPD symptoms tend to get gradually worse over time and can limit normal activities. Smoking speeds up the progression of COPD but it can be extremely hard to quit, and people with COPD tend to have a greater dependence on nicotine. There are several different treatments available that increase people’s chances of successfully quitting smoking; however, many people still relapse back to smoking. Electronic cigarettes (e-cigs) are not currently available on NHS prescription but could help COPD patients to quit smoking. Our goal with this research is to find out how effective e-cigs are compared with combination NRT in helping COPD patients quit smoking cigarettes, and which treatment is more cost-effective for the NHS. The data collected during this trial will also be used to inform a lung health sub-study and wellbeing sub-study. The lung health sub-study will look at the effects of switching to vaping on clinical, physiological and cellular measures of lung health between vapers, continued smokers and quitters. The well-being sub-study will look at the effect of switching to vaping on anxiety, depression and social quality of life compared to those who smoke and quitters.
Who can participate?
People aged 35 years and older who have been identified from selected GP practices and NHS hospitals in England, Wales and Scotland, diagnosed with COPD and are current smokers who want to try to stop smoking
What does the study involve?
This multi-centre trial will invite potentially eligible patients identified from selected GP practices and NHS hospitals in England, Wales and Scotland. Trial participants will be followed up for 1 year. All participants will be asked to have two face-to-face clinic visits to undertake lung function tests and blood tests. Participants will also receive behaviour support calls from a smoking cessation advisor at set time points through the follow-up period.
What are the possible benefits and risks of participating?
All participants will receive support to stop smoking. There is a potential that participants may be successful in quitting smoking and see an improvement in their health. The products used in this trial are widely used for smoking cessation in standard practice and can be bought over the counter. Participants have no higher risk of side effects than if they were to receive either treatment as part of standard care. The use of nicotine-containing products can result in mild side effects and the main participant information sheet (PIS) advises of these and explains what to do/ who to contact if they experience issues. The participants’ GPs will be notified about their participation in the trial, and they will be advised to monitor their patients whilst they try to quit smoking.
Where is the study run from?
University of Birmingham (UK)
When is the study starting and how long is it expected to run for?
September 2022 to January 2027
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
Birmingham Clinical Trials Unit, ECAL@trials.bham.ac.uk (UK)
Contact information
Principal investigator
Centre for Translational Inflammation Research
Queen Elizabeth Hospital
Institute of Inflammation and Ageing
University of Birmingham
Edgbaston
Birmingham
B15 2SQ
United Kingdom
 ORCID ID |
0000-0002-5456-6080 |
|---|---|
| Phone | +44 (0)121 371 3231 |
| d.thickett@bham.ac.uk |
Scientific
Institute of Applied Health Research
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| ORCID ID |
0000-0002-4370-0264 |
|---|---|
| Phone | None available |
| a.c.farley@bham.ac.uk |
Public
Institute of Applied Health Research
College of Medical and Dental Sciences
Public Health Building
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)121 414 8137 |
|---|---|
| ECAL@trials.bham.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multicentre two-arm randomized controlled trial with embedded cost-effectiveness and cohort analyses |
| Secondary study design | Randomised controlled trial |
| Scientific title | Effectiveness of electronic cigarettes compared with combination nicotine replacement therapy for smoking cessation in patients with chronic obstructive pulmonary disease and effect on lung health (ECAL Trial) |
| Study acronym | ECAL |
| Study objectives | To investigate the effectiveness and cost-effectiveness of Electronic Cigarettes for quitting smoking compared with combination Nicotine Replacement Therapy as an aid to smoking cessation. To explore change in lung and mental health in people who switch to vaping compared with people who quit smoking without vaping, and people who continue to smoke. |
| Ethics approval(s) |
Approved 03/10/2023, North East - Newcastle & North Tyneside 2 Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8086; newcastlenorthtyneside2.rec@hra.nhs.uk), ref: 23/NE/0102 |
| Health condition(s) or problem(s) studied | Chronic obstructive pulmonary disease (COPD) |
| Intervention | Intervention arm: Electronic Cigarettes (EC) - At the baseline visit, participants will be given an EC starter pack and an initial supply of e-liquid (up to 20 mg nicotine/ml). Participants will be provided with instructions on how to continue sourcing further supplies themselves from reputable vendors in their preferred nicotine strength and flavours. Comparator arm: Combination Nicotine Replacement Therapy (NRT) - Participants will receive up to a 12-week supply of a nicotine patch plus a fast-acting nicotine product to be used in combination. Participants who do not wish to use patches (e.g. due to previous experience with skin irritation) will be offered two types of fast-acting products. Telephone behavioural support: All participants (intervention and comparator arm) will be advised at the baseline visit that they will receive six weekly behavioural support telephone calls from stop-smoking advisors which will commence within a few days of the baseline visit. During these calls, the advisor will deliver behavioural support according to the National Centre for Smoking Cessation Training Standard Programme including setting a TQD and providing further support around medication use. |
| Intervention type | Drug |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Electronic cigarettes with e-liquid (up to 20 mg nicotine/ml), nicotine patch, fast-acting nicotine product |
| Primary outcome measure(s) |
Abstinence from smoking since target quit date (TQD) biochemically validated (exhaled CO<8ppm), defined in accordance with the Russell Standard. This will be measured with a questionnaire and exhaled carbon monoxide measurement at 52 weeks post-TQD |
| Key secondary outcome measure(s) |
1. Abstinence from smoking for at least 26 weeks biochemically validated (exhaled CO <8 ppm) measured using a questionnaire at 52 weeks |
| Completion date | 05/01/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 35 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 1250 |
| Total final enrolment | 141 |
| Key inclusion criteria | Current inclusion criteria as of 07/01/2026: 1. COPD diagnosis confirmed by post-bronchodilator spirometry (FEV1/FVC <0.7), any GOLD stage 2. Current daily smoker 3. Willing to try to stop smoking using only allocated trial products 4. Aged 35 years or over Previous inclusion criteria: 1. COPD diagnosis previously confirmed by post-bronchodilator spirometry (FEV1/FVC <0.7), any GOLD stage 2. Current smoker (≥5 cigarettes per day) 3. Motivated to stop smoking 4. Aged 35 years or over |
| Key exclusion criteria | Current exclusion criteria as of 07/01/2026: 1. Unable to perform spirometry to a satisfactory standard (e.g. due to dementia, lack of teeth, lack of coordination or not having a good oral seal) 2. Deemed as unsuitable to participate in the trial (e.g. terminal illness, unable to give informed consent) 3. Unable to participate in behaviour support calls 4. Severe angina or unstable cardiovascular disease 5. History of end stage kidney disease 6. History of cirrhosis of the liver 7. Currently taking part in another trial of smoking cessation or COPD treatment/management 8. Contraindications to spirometry within the last 12 weeks – tuberculosis infection, cardiac infarction, retinal detachment, Pneumothorax or surgery on the chest, abdomen, brain, ears or eyes (invite back and re-assess after 12 weeks) Previous exclusion criteria: 1. Unable to perform spirometry to a satisfactory standard (e.g. due to dementia, lack of teeth, lack of coordination or not having a good oral seal) 2. Deemed as unsuitable to participate in the trial (e.g. terminal illness, unable to give informed consent) 3. Unable to participate in behaviour support calls 4. Severe angina or unstable cardiovascular disease 5. History of end stage kidney disease 6. History of cirrhosis of the liver 7. Currently taking NRT, bupropion, varenicline or ECs to stop or reduce smoking 8. Currently taking part in another trial of smoking cessation or COPD treatment/management 9. COPD exacerbation or inpatient hospital stay within the last 8 weeks (invite back and re-assess after 8 weeks) 10. Contraindications to spirometry within the last 12 weeks – tuberculosis infection, cardiac infarction, retinal detachment or surgery on the chest, abdomen, brain, ears or eyes (invite back and re-assess after 12 weeks) |
| Date of first enrolment | 26/06/2024 |
| Date of final enrolment | 21/11/2025 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Wales
Study participating centres
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
England
Beckett Street
Leeds
LS9 7TF
England
Sheriff Hill
Gateshead
NE9 6SX
England
Shrewsbury
SY3 8XQ
England
Chelmsford
CM1 7ET
England
Marton Road
Middlesbrough
TS4 3BW
England
Brighton
BN2 5BE
England
Mansfield Road
Sutton-in-ashfield
NG17 4JL
England
Pensnett Road
Dudley
DY1 2HQ
England
London
SW1P 2PF
England
Rhyl
LL18 5UJ
Wales
Ruislip
HA4 8NX
England
Fountain Street
Ashton-under-lyne
OL6 9RW
England
Manchester
M23 9LT
England
Manchester
M8 5RB
England
Liverpool
L5 8XR
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol (other) | 30/12/2025 | No | No | ||
| Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
07/01/2026: The inclusion and exclusion criteria and study participating centres were updated.
30/12/2025: The following changes were made to the study record:
1. The date of final enrolment was changed from 30/09/2025 to 21/11/2025.
2. The completion date was changed from 31/12/2026 to 05/01/2027.
3. Protocol and total final enrolment added.
17/09/2025: The date of final enrolment was changed from 30/09/2025 to 31/12/2025.
20/08/2025: The following changes were made to the study record:
1. The date of final enrolment was changed from 10/08/2025 to 30/09/2025.
2. The completion date was changed from 30/09/2025 to 31/12/2026.
12/07/2024: The recruitment start date was changed from 03/06/2024 to 26/06/2024.
20/06/2024: The recruitment start date was changed from 10/06/2024 to 03/06/2024.
03/06/2024: The recruitment start date was changed from 10/05/2024 to 10/06/2024.
11/04/2024: The following changes were made:
1. Phase added.
2. Study website added.
3. The recruitment start date was changed from 01/03/2024 to 10/05/2024.
4. The recruitment end date was changed from 30/09/2024 to 10/08/2025.
5. The following study participating centres were added: Leeds Teaching Hospitals NHS Trust, Gateshead Health NHS Foundation Trust and The Shrewsbury and Telford Hospital NHS Trust.
02/11/2023: Internal review.
04/10/2023: ISRCTN received notification of combined HRA/MHRA approval for this trial on 04/10/2023
03/05/2023: Trial's existence confirmed by Health Research Authority (HRA) (UK).
