The Use of Nicotine Patches Together With E-cigarettes (With and Without Nicotine) for Smoking Cessation (ASCEND-II)

A Randomised-controlled Clinical Trial to Evaluate the Effectiveness and Safety of Combining Nicotine Patches With E-cigarettes (With and Without Nicotine) Plus Behavioural Support, on Smoking Abstinence

A randomised trial to determine whether e-cigarettes (with and without nicotine) combined with nicotine patches and behavioural support can assist smokers in remaining abstinent for at least six months.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Nicotine patch; Behavioral: Behavioural support; Device: e-cigarette; Drug: Nicotine

Detailed Description

A pragmatic, double-blind, three-arm randomised controlled trial undertaken in New Zealand to determine whether e-cigarettes combined with nicotine patches can assist smokers in remaining abstinent for at least six months. 1809 smokers who are motivated to quit will be recruited from the community using media advertising and randomly allocated to one of three groups, namely 1) 21mg nicotine patch daily, 2) 21mg nicotine patch daily plus a 'new generation' e-cigarette with no nicotine or 3) 21mg nicotine patch daily plus a 'new generation' e-cigarettes with nicotine. Participants will be instructed to start using the study products two weeks prior to their quit date, and continue for a further 12 weeks after their quit date. Participants will also receive a cessation behavioural support programme consisting of at least six follow-up telephone calls (10-15 minutes each) over the first six weeks. Outcome data will be collected on the participant's set quit date, then one, three, six and (for some but not all) 12 months post-quit date.

• Study Type: Interventional
• Enrollment (Actual): 1124
• Phase: Phase 3

Contacts and Locations

Study Locations

• New Zealand
  • North Island
    • Auckland, North Island, New Zealand, 1072
      • National Institute for Health Innovation, University of Auckland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Smoke and want to quit in the next three months
• Reside in New Zealand
• At least 18 years of age
• Able to provide verbal consent
• Have access to telephone (mobile and/or landline)
• Are prepared to use a nicotine patch or a nicotine patch and e-cigarette together.
• Only one person per household is eligible.

Exclusion Criteria:

• Pregnant women
• Women who are breastfeeding
• Current users of NRT products
• People currently enrolled in another smoking cessation programme or other cessation study
• People who have used an e-cigarette for more than one week in the last year for smoking cessation
• Current users of non-nicotine based cessation therapies (e.g. buproprion, clonidine, nortriptyline or varenicline).
• People who have had a heart attack, stroke or severe angina within the previous two weeks.
• People who self-report a history of severe allergies and/or poorly controlled asthma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patch; 21mg nicotine patch daily for 14 weeks (including a 2 week prequit period) plus behavioural support for six weeks post-quit	Drug: Nicotine patch; A transdermal patch that slowly releases nicotine into the body through the skin.; Other Names: Nicotine replacement therapy; Behavioral: Behavioural support; Withdrawal-oriented behavioural support; Other Names: Smoking cessation behavioural support
Active Comparator: Patch and nicotine-free e-cigarette; 21mg nicotine patch (daily) and nicotine-free e-cigarette (ad libitum) for 14 weeks (including a 2 week prequit period), plus behavioural support for six weeks post-quit	Drug: Nicotine patch; A transdermal patch that slowly releases nicotine into the body through the skin.; Other Names: Nicotine replacement therapy; Behavioral: Behavioural support; Withdrawal-oriented behavioural support; Other Names: Smoking cessation behavioural support; Device: e-cigarette; A electronically powered device that delivers to the user an aerosol of propylene glycol and/or glycerine, with or without flavourings and nicotine.; Other Names: electronic cigarette; electronic nicotine delivery device
Active Comparator: Patch and nicotine e-cigarette; 21mg nicotine patch (daily) and nicotine e-cigarette (ad libitum) for 14 weeks (including a 2 week prequit period), plus behavioural support for six weeks post-quit	Drug: Nicotine patch; A transdermal patch that slowly releases nicotine into the body through the skin.; Other Names: Nicotine replacement therapy; Behavioral: Behavioural support; Withdrawal-oriented behavioural support; Other Names: Smoking cessation behavioural support; Device: e-cigarette; A electronically powered device that delivers to the user an aerosol of propylene glycol and/or glycerine, with or without flavourings and nicotine.; Other Names: electronic cigarette; electronic nicotine delivery device; Drug: Nicotine; Nicotine contained in e-liquid (e-juice) used in e-cigarettes; Other Names: Nicotine liquid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous abstinence (Russell Standard)	Self-report of smoking not more than five cigarettes from the Quit date, supported by biochemical validation (expired air carbon monoxide).	Six months post quit date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous abstinence	Self-report of smoking not more than five cigarettes from the Quit date	One, three and 12 months post quit date
7-day point prevalence abstinence	Self-report of having smoked no cigarettes (not even a puff) in the past seven days, with biochemical verification at six months only	Participant's set quit date, then one, three, six and 12 months post quit date
Number of cigarettes smoked	Self-report of number of cigarettes smoked per day (or when smoking for non-daily smokers)	Participant's set quit date, then one, three, six and 12 months post quit date
Smoking reduction	Defined as reducing consumption by at least 25% (in terms of numbers of cigarettes per day or weight of loose tobacco per day or when smoking for non-daily smokers), at all time points.	Participant's set quit date, then one, three, six and 12 months post quit date
Time to relapse	Time to relapse back to daily smoking from quit date	One, three, and six months post quit date
Withdrawal	The physical signs and symptoms associated with withdrawal, measured using the Mood and Physical Symptoms Scale (MPSS).	Participant's set quit date, then at one month post quit date
Self-efficacy	Self-rated chances of quitting, measured on a scale of 1-5 where 1=very low and 5=very high	Participant's set quit date
Use of any other smoking cessation methods/products	Participants will be asked whether they used any non-NRT methods of cessation since the last assessment (Yes/No), and if yes, when they started using it, the type they used, and frequency of use.	Participant's set quit date, then one, three, six and 12 months post quit date
Serious adverse events		Participant's set quit date, then one, three, six and 12 months post quit date
Cost	Cost outcomes will be derived from known costs of the various products include cost per quitter and cost per person reducing their daily cigarette consumption. The tobacco expenditure savings to individual smokers will also be calculated using data on the daily amount smoked prior to quitting and the average price of cigarettes at the time.	Participant's set quit date, then one, three, six and 12 months post quit date
Medication compliance	How frequently they used their allocated product	Participant's set quit date, then one and three months post quit date
Crossover	Participants in the patch only arm will be asked whether they accessed and used an e-cigarette (with or without nicotine) during the trial (Yes/No) and at what time during the trial.	Participant's set quit date, then one, three, six and 12 months post quit date
Additional e-cigarette support	Participants allocated to the e-cigarette groups will be asked whether they accessed any on-line e-cigarette support networks during the trial (Yes/No) and if so what these were (free text), and at what time during the trial.	Participant's set quit date, then one, three, six and 12 months post quit date
Dual use	Defined as use of both allocated treatment and continued smoking of cigarettes	Participant's set quit date, then one, three, six and 12 months post quit date
Continuation of treatment use	Defined as continued use of allocated treatment after the end of the designated treatment period (12 weeks post-quit).	Six and 12 months post quit date
Perception of their allocated product(s)	Participants will be asked what they liked and disliked about their allocated products (free text)	Participant's set quit date, then one and three months post quit date
Recommendations	Participant's will be asked whether they would recommend their allocated treatment to another smoker who wanted to quit (Yes/No)	Participant's set quit date, then one and three months post quit date

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand
• Collaborators: Auckland District Health Board; Health New Zealand Ltd, Christchurch, New Zealand
• Investigators: Principal Investigator: Natalie Walker, PhD, National Institute for Health Innovation, School of Population Health, University of Auckland

Publications and helpful links

General Publications

• Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4.
• Walker N, Verbiest M, Kurdziel T, Laking G, Laugesen M, Parag V, Bullen C. Effectiveness and safety of nicotine patches combined with e-cigarettes (with and without nicotine) for smoking cessation: study protocol for a randomised controlled trial. BMJ Open. 2019 Feb 25;9(2):e023659. doi: 10.1136/bmjopen-2018-023659.
• Walker N, Parag V, Verbiest M, Laking G, Laugesen M, Bullen C. Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial. Lancet Respir Med. 2020 Jan;8(1):54-64. doi: 10.1016/S2213-2600(19)30269-3. Epub 2019 Sep 9.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: August 9, 2015
• First Submitted That Met QC Criteria: August 11, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Smoking Cessation; Nicotine Patch; Electronic Cigarettes
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: U1111-1172-9632

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)