Cytisine Versus Varenicline for Smoking Cessation (RAUORA)

• ClinicalTrials.gov Identifier: NCT02957786
• Recruitment Status: Completed
• First Posted: November 8, 2016
• Last Update Posted: August 19, 2021
• Sponsor: University of Auckland, New Zealand
• Collaborators: Lakes District Health Board; Brunel University
• Information provided by (Responsible Party): Natalie Walker, University of Auckland, New Zealand

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Smoking Cessation	Drug: Cytisine; Behavioral: Behavioural support; Drug: Varenicline	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 679 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: RAUORA: Cytisine Versus Varenicline for Smoking Cessation
• Actual Study Start Date: September 18, 2017
• Actual Primary Completion Date: October 10, 2019
• Actual Study Completion Date: October 10, 2019

Arms and Interventions

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 Name: 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 Name: Champix

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Continuous abstinence from smoking [ Time Frame: One month post-quit date ]
   Self-report of smoking not more than five cigarettes from the quit date
2. Continuous abstinence from smoking [ Time Frame: Three months post-quit date ]
   Self-report of smoking not more than five cigarettes from the quit date
3. Continuous abstinence from smoking [ Time Frame: 12 months post-quit date (in 2/3 of sample) ]
   Self-report of smoking not more than five cigarettes from the quit date, supported by biochemical validation using a carbon monoxide (CO) expired breath
4. 7-day point prevalence abstinence from smoking [ Time Frame: One month post-quit date ]
   Self-report of having smoked no cigarettes (not even a puff) in the past seven days.
5. 7-day point prevalence abstinence from smoking [ Time Frame: Three month post-quit date ]
   Self-report of having smoked no cigarettes (not even a puff) in the past seven days.
6. 7-day point prevalence abstinence from smoking [ Time Frame: Six month post-quit date ]
   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.
7. 7-day point prevalence abstinence from smoking [ Time Frame: 12 month post-quit date (in 2/3 of sample) ]
   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.
8. Time to relapse back to smoking [ Time Frame: One month post-quit date ]
   Defined as return to daily smoking.
9. Time to relapse back to smoking [ Time Frame: Three month post-quit date ]
   Defined as return to daily smoking.
10. Time to relapse back to smoking [ Time Frame: Six month post-quit date ]
    Defined as return to daily smoking.
11. Time to relapse back to smoking [ Time Frame: 12 month post-quit date (in 2/3 of sample) ]
    Defined as return to daily smoking.
12. Cigarette withdrawal [ Time Frame: One month post-quit date ]
    The physical signs and symptoms associated with nicotine withdrawal over the last week, measured using the Mood and Physical Symptoms Scale (MPSS)
13. Cigarette withdrawal [ Time Frame: Three months post-quit date ]
    The physical signs and symptoms associated with nicotine withdrawal over the last week, measured using the Mood and Physical Symptoms Scale (MPSS)
14. Cigarette withdrawal [ Time Frame: Six months post-quit date ]
    The physical signs and symptoms associated with nicotine withdrawal over the last week, measured using the Mood and Physical Symptoms Scale (MPSS)
15. Cigarettes per day [ Time Frame: One month post-quit date ]
    Number of cigarettes smoked per day, if smoking
16. Cigarettes per day [ Time Frame: Three month post-quit date ]
    Number of cigarettes smoked per day, if smoking
17. Cigarettes per day [ Time Frame: Six month post-quit date ]
    Number of cigarettes smoked per day, if smoking
18. Cigarettes per day [ Time Frame: 12 month post-quit date (in 2/3 of sample) ]
    Number of cigarettes smoked per day, if smoking
19. Smoking satisfaction, if smoking [ Time Frame: One month post-quit date ]
    Measured using the modified Cigarette Evaluation Questionnaire (mCEQ).
20. Smoking satisfaction, if smoking [ Time Frame: Three month post-quit date ]
    Measured using the modified Cigarette Evaluation Questionnaire (mCEQ).
21. Smoking satisfaction, if smoking [ Time Frame: Six month post-quit date ]
    Measured using the modified Cigarette Evaluation Questionnaire (mCEQ).
22. Health-related quality of life [ Time Frame: One month post-quit date ]
    Measured using the New Zealand EQ-5D Tariff 2
23. Health-related quality of life [ Time Frame: Three months post-quit date ]
    Measured using the New Zealand EQ-5D Tariff 2
24. Health-related quality of life [ Time Frame: Six months post-quit date ]
    Measured using the New Zealand EQ-5D Tariff 2
25. Acceptability of allocated treatment [ Time Frame: One month post-quit date ]
    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).
26. Acceptability of allocated treatment [ Time Frame: Three months post-quit date ]
    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).
27. Use of other methods of cessation [ Time Frame: One month post-quit date ]
    Participants will be asked about their use of other methods of cessation, such as NRT, Zyban, clonidine, nortriptyline, e-cigarettes, acupuncture etc.
28. Use of other methods of cessation [ Time Frame: Three months post-quit date ]
    Participants will be asked about their use of other methods of cessation, such as NRT, Zyban, clonidine, nortriptyline, e-cigarettes, acupuncture etc.
29. Use of other methods of cessation [ Time Frame: Six months post-quit date ]
    Participants will be asked about their use of other methods of cessation, such as NRT, Zyban, clonidine, nortriptyline, e-cigarettes, acupuncture etc.
30. Medication compliance [ Time Frame: One month post-quit date ]
    Self-reported pill count, early stopping of allocated medication and reasons why.
31. Medication compliance [ Time Frame: Three months post-quit date ]
    Self-reported pill count, early stopping of allocated medication and reasons why.
32. Adverse events [ Time Frame: One month post-quit date ]
    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.
33. Adverse events [ Time Frame: Three month post-quit date ]
    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.
34. Adverse events [ Time Frame: Six month post-quit date ]
    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.
35. Adverse events [ Time Frame: 12 month post-quit date (in 2/3 of sample) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

New Zealand

National Institute for Health Innovation, University of Auckland

Auckland, North Island, New Zealand, 1072

Sponsors and Collaborators

University of Auckland, New Zealand

Lakes District Health Board

Brunel University

Investigators

• Principal Investigator: Natalie Walker, PhD; University of Auckland, New Zealand

More Information

Publications of Results:

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.

Other 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.

• Responsible Party: Natalie Walker, Associate Professor, University of Auckland, New Zealand
• ClinicalTrials.gov Identifier: NCT02957786
• Other Study ID Numbers: UTN: U1111-1187-2838
• First Posted: November 8, 2016
• Last Update Posted: August 19, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD analysis planned - details of plan not yet finalized

• 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

Keywords provided by Natalie Walker, University of Auckland, New Zealand:

cytisine; varenicline; smoking cessation; indigenous

Additional relevant MeSH terms:

Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs