Condition category
Mental and Behavioural Disorders
Date applied
11/12/2009
Date assigned
21/01/2010
Last edited
18/03/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof David Wood

ORCID ID

Contact details

5th floor
North Wing
Imperial College London
Charing Cross Hospital
St Dunstan's Rd
London
W6 8RP
United Kingdom
+44 (0)20 8846 7352
d.wood@imperial.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

EUROACTION PLUS intensive smoking intervention: a randomised controlled trial of a smoking cessation programme with varenicline versus usual care

Acronym

EUROACTION PLUS

Study hypothesis

The aim of the study is to demonstrate that a smoking cessation programme including varenicline in patients with coronary or other vascular disease, and in people at high risk of developing future cardiovascular disease delivered in the context of a preventive cardiology programme will provide fast, effective smoking cessation and is effective and generalisable in every day clinical practice.

The expectation is that varenicline will provide fast, effective smoking cessation in patients enrolled to a preventive cardiology programme. The EUROACTION network of primary care centres provides a unique opportunity to demonstrate the effectiveness of varenicline in the context of a recently conducted randomised controlled trial (EUROACTION) which had no significant impact on smoking cessation in primary care. This new trial will be based in the EUROACTION primary care intervention centres and patients who are at high cardiovascular risk and smoking will be randomised to the preventive cardiology programme and varenicline, or to receive usual care within these centres. As the EUROACTION programme is no longer running in these centres following completion of the trial, usual care for current cigarette smokers is advice only from the general practitioner. In this trial we will provide a nurse coordinated smoking cessation service including varenicline treatment in the context of a preventive cardiology programme based on the EUROACTION model. This design has the advantage of building on the experience of the EUROACTION model for preventive cardiology by testing the additional benefits of a more intensive smoking cessation intervention including varenicline in the context of a proven preventive cardiology programme. The cost-effectiveness of this smoking cessation intervention will also be evaluated.

Ethics approval

1. UK: Leicestershire, Northamptonshire and Rutland Research Ethics Committee 2 approved on the 23/09/2009 (ref: 09/H0402/8S)
2. Spain: not provided at time of registration
3. Italy: not provided at time of registration
4. Netherlands: not provided at time of registration

All other centres will seek ethics approval before recruiting participants.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Smoking cessation

Intervention

The EUROACTION programme is a comprehensive, nurse co-ordinated lifestyle programme addressing smoking cessation (with the option of using varenicline), healthy eating and increased physical activity together with assessment and management of other cardiovascular risk factors.

In the intervention arm, the cardiovascular screening and risk assessment will be performed at the initial and 16-week interview for all patients and their partners. This will include smoking status, diet, physical activity, blood pressure, lipids, and diabetes management. Some psychosocial measurements including assessment of anxiety and depression and quality of life will also be undertaken. All participants will be offered comprehensive, family-based, preventive cardiology programme, including intensive smoking cessation intervention with varenicline (for all patients and partners who are smokers).

The EUROACTION PLUS varenicline programme will be focused on all aspects of lifestyle and other cardiovascular risk factor management. The programme is coordinated by specialist cardiac nurses. In each practice, the team is made up of two cardiac specialist nurses, and the general practitioners (GPs). Patients randomised to the EUROACTION PLUS varenicline programme will be assessed by the nurse together with their partners. The nurse is specially trained to address smoking cessation, diet and physical activity. The GPs work with the specialist nurse to ensure that patients and their partners receive varenicline. The GPs will also be responsible for prescribing and up titrating drugs to achieve the blood pressure, cholesterol and glucose targets.

Smoking cessation management:
Varinecline will be introduced within the first 4 weeks after baseline assessment and will be initiated 1 week before the patient's chosen quit date. The dose of varenicline will be titrated as follows: 0.5 mg for days 1 to 3, 0.5 mg twice per day on days 4 to 7, then 1 mg twice per day through week 12. The target quit date will be within 4 weeks of starting varenicline.

Varenicline tartrate is supplied for oral administration in two strengths: 0.5 mg capsular biconvex white to off-white, film-coated tablets or 1 mg capsular biconvex light blue film coated tablets. Varenicline tartrate will be administered orally with meal or snack. During the first week of the study, tablets containing 0.5 mg varenicline tartrate will be administered. During the remaining 11 weeks of the study, tablets containing 1 mg varenicline tartrate will be administered. Additional information can be found in the local SmPC.

Varenicline will be supplied free of charge by Pfizer and will be delivered to the GPs before the start of EUROACTION programme. Commercial supplies will be used. No additional label is necessary.

Intervention type

Drug

Phase

Not Applicable

Drug names

Varenicline

Primary outcome measures

Seven-day point (period) prevalence of non-smoking at 16 weeks. The smoking cessation will be validated by breath carbon monoxide (CO) less than 10 ppm. Patients will be classified as non-smokers if they are not smoking in the week prior to their 16 week assessment even if they have relapsed several times in the intervening period. If they are smoking in that same week, and/or breath CO is raised, they will be classified as smokers. The primary outcome is the prevalence of non-smokers in intervention compared to usual care.

The proportions of vascular patients and high risk individuals who achieve the primary outcome at 16 weeks will be analysed separately for each of these two diagnostic groups. Partners will be analysed separately but this is not a pre-specified end point and there are no power calculations. However, in a family based intervention it's important to offer the partners the same package, including the smoking cessation intervention. We estimate the number of smoking partners to be about 60% from EUROACTION. This high figure is expected given the concordance for smoking within families. We assume that at least one quarter of all partners who smoke will want to try to quit smoking.

Secondary outcome measures

Measured at 16 week follow-up:
1. Number of smoking relapses in intervention. Smoking relapse is defined as "the time to last cigarette from the start of varenicline"
2. Adverse effects
3. Proportions of patients achieving European and national lifestyle, risk factors and therapeutic targets for cardiovascular disease prevention:
3.1. Smoking (self reported, breath CO)
3.2. Diet/nutrition (self reported, food habit questionnaire)
3.3. Physical activity (self reported, step counter, Chester step test, Duke Activity Status Index [DASI] physical activity questionnaire)
3.4. Overweight/obesity (body mass index (BMI), waist circumference)
3.5. Diabetes (known/new, fasting and random plasma glucose, glycated haemoglobin [Hb A1c] in patients with diabetes)
3.6. Blood pressure
3.7. Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, calculated low-density lipoprotein (LDL) cholesterol
3.8. Smoking cessation drug therapies:
3.8.1. Varenicline
3.8.2. Nicotine replacement therapy
3.8.3. Bupropion hydrochloride
3.9. Cardioprotective drug therapies
4. Patient reported outcomes: Hospital Anxiety and Depression Scale (HADS), Quality of Life (EQ-5D)

Overall trial start date

01/12/2009

Overall trial end date

30/12/2010

Reason abandoned

Eligibility

Participant inclusion criteria

Vascular patients and partners:
1. Patients with a medical diagnosis of coronary or other atherosclerotic disease:
1.1. Acute myocardial infarction (ST segment elevation myocardial infarction [STEMI] or non-ST segment elevation myocardial infarction [NSTEMI])
1.2. Unstable angina
1.3. Stable angina pectoris
1.4. Elective revascularisation: coronary artery bypass graft (CABG), percutaneous transluminal angioplasty (PTCA)
1.5. Stroke
1.6. Transient ischaemic attack (TIA)
1.7. Peripheral vascular disease (PVD)
2. Have been smoking 5 or more cigarettes per day within the last month
3. Willing to make a quit attempt
4. Aged 18 years of age or older, but less than 80 years, either sex

The partners of all recruited coronary patients will also be identified and invited to participate in the preventive cardiology programme. Those who are smoking will also be offered the same smoking cessation service including varenicline.

High-risk people and partners:
1. Have been smoking 5 or more cigarettes per day within the last month
2. Willing to make a quit attempt
3. Men and women, 50 years of age or older, but less than 80 years, either sex
4. Either:
4.1. Newly identified high multifactorial risk individuals: CVD risk equal or greater than 5% over 10 years (now or projected to age 60 years), according to the HeartScore risk estimation system; or
4.2. Have been treated with antihypertensive and/or lipid-lowering therapies; or
4.3. Have diabetes mellitus

The partners of all recruited high risk patients will also be identified and invited to participate in the preventive cardiology programme. Those who are smoking will also be offered the same smoking cessation service including varenicline.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1060

Participant exclusion criteria

Vascular patients:
1. Severe heart failure
2. Severe physical disability
3. Impaired cognitive function
4. Patients with acute coronary syndromes, with or without revasularisation, will not be included in the study until 2 weeks has elapsed following their coronary event
5. Hypersensitivity to varenicline (active substance or to any of the inactive ingredients)
6. History of suicidal attempt
7. History of psychosis
8. Bipolar disorders
9. Panic disorders
10. Epilepsy
11. History of alcohol dependence

High-risk people:
1. History of coronary or other atherosclerotic disease
2. Severe heart failure
3. Severe physical disability
4. Impaired cognitive function
5. Hypersensitivity to varenicline (active substance or to any of the inactive ingredients)
6. History of suicidal attempt within the last 10 years
7. History of psychosis
8. Bipolar disorders
9. Panic disorders
10. Epilepsy
11. History of alcohol dependence

Recruitment start date

01/12/2009

Recruitment end date

30/12/2010

Locations

Countries of recruitment

Denmark, Italy, Netherlands, Spain, United Kingdom

Trial participating centre

5th floor, North Wing
London
W6 8RP
United Kingdom

Sponsor information

Organisation

Imperial College London (UK)

Sponsor details

Clinical Research Governance Office
G02
Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
United Kingdom
+44 (0)20 7594 1188
gary.roper@imperial.ac.uk

Sponsor type

University/education

Website

http://www3.imperial.ac.uk/

Funders

Funder type

Industry

Funder name

Pfizer Limited (UK)

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

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24616337

Publication citations

  1. Results

    Jennings C, Kotseva K, De Bacquer D, Hoes A, de Velasco J, Brusaferro S, Mead A, Jones J, Tonstad S, Wood D, , Effectiveness of a preventive cardiology programme for high CVD risk persistent smokers: the EUROACTION PLUS varenicline trial., Eur. Heart J., 2014, 35, 21, 1411-1420, doi: 10.1093/eurheartj/ehu051.

Additional files

Editorial Notes