Cytisine Versus Varenicline for Smoking Cessation (RAUORA)

RAUORA: Cytisine Versus Varenicline for Smoking Cessation

To evaluate the effectiveness, safety, and cost-effectiveness of cytisine plus behavioural support compared to varenicline plus behavioural support for smoking cessation, in indigenous Māori (or family of Māori) who smoke and are motivated to quit.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Cytisine; Behavioral: Behavioural support; Drug: Varenicline

Detailed Description

Cytisine, a natural product, found in plants such as the Golden Rain and New Zealand Kowhai, partially blocks the effects of nicotine on the brain. Cytisine has been used as a smoking cessation treatment in several Central and Eastern European countries since the 1960s, is inexpensive compared to other cessation medications and has few known side effects. New Zealand research has shown cytisine to be more effective than nicotine replacement therapy at helping people quit smoking. Using a clinical trial design (N=2140) the investigators plan to investigate whether cytisine is at least as good as varenicline (the most effective, but most expensive, smoking cessation medication currently available in New Zealand) for helping Māori/family of Māori who smoke, to quit.

• Study Type: Interventional
• Enrollment (Actual): 679
• 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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• daily tobacco smokers
• self-identify as Māori (indigenous New Zealander) or whānau (family) of Māori
• want to stop smoking in the next two weeks
• are at least 18 years of age
• are able to provide verbal consent
• reside in the Lakes District Health Board, Eastern Bay of Plenty or Tokoroa region at the time of enrolment
• have daily access to a mobile phone with text capability and/or email and access to the internet via computer or smartphone
• are eligible for subsidised varenicline under special authority conditions

Exclusion Criteria:

• are pregnant or breastfeeding
• are current users of other smoking cessation therapies (e.g. nicotine replacement therapy [NRT], buproprion [Zyban], clonidine, nortriptyline, e-cigarettes)
• are enrolled in another smoking cessation programme or another smoking cessation study
• have a contraindication for cytisine or varenicline
• have used varenicline or cytisine in the past 12 months
• have another person in their household involved in the trial
• have moderate or severe renal impairment,
• are being treated for active or latent TB
• have been treated for a heart attack, stroke, or severe angina within the last two weeks
• have uncontrolled high blood pressure (> 150 mmHg systolic, > 100 mmHg diastolic)
• have a history of seizures

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cytisine plus behavioural support; 12-week course of cytisine capsules (1.5mg), with a decreasing dosing regimen (9mg/day for days 1-3, 7.5mg/day for days 4-12, 6mg/day for days 13-16, 4.5mg/day for days 17-20, 3.0mg/day from days 21-week 12). Participants will be asked to reduce their smoking over the first four days of treatment so that they are not smoking at all by the fifth day, which will be their designated Quit date. Participants will also withdrawal-orientated behavioural support (delivered by cessation advisors), in addition to brief cessation advice from the study-specific doctor (at the point that the prescription is provided) and community pharmacist (at the point the participant redeems their prescription).	Drug: Cytisine; Cytisine tablets; Other Names: Tabex; Behavioral: Behavioural support; Withdrawal-orientated cessation support
Active Comparator: Varenicline plus behavioural support; 12-week course of Varenicline tablets (0.5mg/1mg), with an increasing dosing regimen (0.5mg/day for days 1-3, 1.0mg/day for days 4-7, 2.0mg/day for day 8-week 12). Participants will be asked to reduce their smoking over the first four days of treatment so that they are not smoking at all by the fifth day, which will be their designated Quit date. Participants will also receive withdrawal-orientated behavioural support (delivered by cessation advisors), in addition to brief cessation advice from the study-specific doctor (at the point that the prescription is provided) and community pharmacist (at the point the participant redeems their prescription).	Behavioral: Behavioural support; Withdrawal-orientated cessation support; Drug: Varenicline; Varenicline tablets; Other Names: Champix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous abstinence from smoking	Self-report of smoking not more than five cigarettes from the quit date, supported by biochemical validation using a carbon monoxide (CO) expired breath	Six months post-quit date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous abstinence from smoking	Self-report of smoking not more than five cigarettes from the quit date	One month post-quit date
Continuous abstinence from smoking	Self-report of smoking not more than five cigarettes from the quit date	Three months post-quit date
Continuous abstinence from smoking	Self-report of smoking not more than five cigarettes from the quit date, supported by biochemical validation using a carbon monoxide (CO) expired breath	12 months post-quit date (in 2/3 of sample)
7-day point prevalence abstinence from smoking	Self-report of having smoked no cigarettes (not even a puff) in the past seven days.	One month post-quit date
7-day point prevalence abstinence from smoking	Self-report of having smoked no cigarettes (not even a puff) in the past seven days.	Three month post-quit date
7-day point prevalence abstinence from smoking	Self-report of having smoked no cigarettes (not even a puff) in the past seven days,supported by biochemical validation using a carbon monoxide (CO) expired breath.	Six month post-quit date
7-day point prevalence abstinence from smoking	Self-report of having smoked no cigarettes (not even a puff) in the past seven days,supported by biochemical validation using a carbon monoxide (CO) expired breath.	12 month post-quit date (in 2/3 of sample)
Time to relapse back to smoking	Defined as return to daily smoking.	One month post-quit date
Time to relapse back to smoking	Defined as return to daily smoking.	Three month post-quit date
Time to relapse back to smoking	Defined as return to daily smoking.	Six month post-quit date
Time to relapse back to smoking	Defined as return to daily smoking.	12 month post-quit date (in 2/3 of sample)
Cigarette withdrawal	The physical signs and symptoms associated with nicotine withdrawal over the last week, measured using the Mood and Physical Symptoms Scale (MPSS)	One month post-quit date
Cigarette withdrawal	The physical signs and symptoms associated with nicotine withdrawal over the last week, measured using the Mood and Physical Symptoms Scale (MPSS)	Three months post-quit date
Cigarette withdrawal	The physical signs and symptoms associated with nicotine withdrawal over the last week, measured using the Mood and Physical Symptoms Scale (MPSS)	Six months post-quit date
Cigarettes per day	Number of cigarettes smoked per day, if smoking	One month post-quit date
Cigarettes per day	Number of cigarettes smoked per day, if smoking	Three month post-quit date
Cigarettes per day	Number of cigarettes smoked per day, if smoking	Six month post-quit date
Cigarettes per day	Number of cigarettes smoked per day, if smoking	12 month post-quit date (in 2/3 of sample)
Smoking satisfaction, if smoking	Measured using the modified Cigarette Evaluation Questionnaire (mCEQ).	One month post-quit date
Smoking satisfaction, if smoking	Measured using the modified Cigarette Evaluation Questionnaire (mCEQ).	Three month post-quit date
Smoking satisfaction, if smoking	Measured using the modified Cigarette Evaluation Questionnaire (mCEQ).	Six month post-quit date
Health-related quality of life	Measured using the New Zealand EQ-5D Tariff 2	One month post-quit date
Health-related quality of life	Measured using the New Zealand EQ-5D Tariff 2	Three months post-quit date
Health-related quality of life	Measured using the New Zealand EQ-5D Tariff 2	Six months post-quit date
Acceptability of allocated treatment	Participants will be asked for their views on the use of their allocated medication as a cessation aid (i.e. whether they would recommend the treatment to another smoker and the things they liked or disliked about using the product).	One month post-quit date
Acceptability of allocated treatment	Participants will be asked for their views on the use of their allocated medication as a cessation aid (i.e. whether they would recommend the treatment to another smoker and the things they liked or disliked about using the product).	Three months post-quit date
Use of other methods of cessation	Participants will be asked about their use of other methods of cessation, such as NRT, Zyban, clonidine, nortriptyline, e-cigarettes, acupuncture etc.	One month post-quit date
Use of other methods of cessation	Participants will be asked about their use of other methods of cessation, such as NRT, Zyban, clonidine, nortriptyline, e-cigarettes, acupuncture etc.	Three months post-quit date
Use of other methods of cessation	Participants will be asked about their use of other methods of cessation, such as NRT, Zyban, clonidine, nortriptyline, e-cigarettes, acupuncture etc.	Six months post-quit date
Medication compliance	Self-reported pill count, early stopping of allocated medication and reasons why.	One month post-quit date
Medication compliance	Self-reported pill count, early stopping of allocated medication and reasons why.	Three months post-quit date
Adverse events	Any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not it is considered related to the product.	One month post-quit date
Adverse events	Any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not it is considered related to the product.	Three month post-quit date
Adverse events	Any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not it is considered related to the product.	Six month post-quit date
Adverse events	Any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not it is considered related to the product.	12 month post-quit date (in 2/3 of sample)

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand
• Collaborators: Brunel University; Lakes District Health Board
• Investigators: Principal Investigator: Natalie Walker, PhD, University of Auckland, New Zealand

Publications and helpful links

General Publications

• Walker N, Smith B, Barnes J, Verbiest M, Kurdziel T, Parag V, Pokhrel S, Bullen C. Cytisine versus varenicline for smoking cessation for Maori (the indigenous people of New Zealand) and their extended family: protocol for a randomized non-inferiority trial. Addiction. 2019 Feb;114(2):344-352. doi: 10.1111/add.14449. Epub 2018 Nov 9.
• Walker N, Smith B, Barnes J, Verbiest M, Parag V, Pokhrel S, Wharakura MK, Lees T, Cubillos Gutierrez H, Jones B, Bullen C. Cytisine versus varenicline for smoking cessation in New Zealand indigenous Maori: a randomized controlled trial. Addiction. 2021 Oct;116(10):2847-2858. doi: 10.1111/add.15489. Epub 2021 May 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2017
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): October 10, 2019

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (Estimate): November 8, 2016

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; varenicline; indigenous; cytisine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: UTN: U1111-1187-2838

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD analysis planned - details of plan not yet finalized

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No