Cytisine Versus Varenicline for Smoking Cessation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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RAUORA: Cytisine Versus Varenicline for Smoking Cessation

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Cytisine
* Behavioral: Behavioural support
* Drug: Varenicline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cytisine plus behavioural support<br>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<br>* Cytisine tablets<br>* Other names: Tabex;Behavioral: Behavioural support<br>* Withdrawal-orientated cessation support<br>|
| Active Comparator: Varenicline plus behavioural support<br>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<br>* Withdrawal-orientated cessation support<br>Drug: Varenicline<br>* Varenicline tablets<br>* Other names: Champix;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, cytisine, varenicline, indigenous