Cytisine versus varenicline for smoking cessation for Māori (the indigenous people of New Zealand) and their extended family: protocol for a randomized non-inferiority trial

Natalie Walker, Barry Smith, Joanne Barnes, Marjolein Verbiest, Tomasz Kurdziel, Varsha Parag, Subhash Pokhrel, Chris Bullen, Natalie Walker, Barry Smith, Joanne Barnes, Marjolein Verbiest, Tomasz Kurdziel, Varsha Parag, Subhash Pokhrel, Chris Bullen

Abstract

Background and aims: Cytisine, a nicotinic acetylcholine receptor partial agonist (like varenicline) found in some plants, is a low-cost, effective smoking cessation medication that may appeal to Māori [the indigenous people of New Zealand (NZ)]. The RAUORA trial aims to determine the effectiveness, safety and cost-effectiveness of cytisine (Tabex® ) versus varenicline (Champix® ) for smoking cessation in Māori and the whānau (extended family) of Māori.

Design: Pragmatic, community-based, open-label randomized non-inferiority trial.

Setting: Lakes District Health Board region, NZ.

Participants: Daily smokers (n = 2140) who self-identify as Māori or whānau of Māori, and are: aged ≥ 18 years, motivated to quit smoking in the next 2 weeks, eligible for subsidized varenicline, able to provide verbal consent and have daily access to a mobile phone/internet. Recruitment uses multi-media advertising.

Intervention and comparator: Participants are randomized (1 : 1 ratio) to receive a prescription for 12 weeks of cytisine tablets [following the manufacturer's dosing regimen for 25 days, then one 1.5-mg tablet every 6 hours (two per day) until 12 weeks] or varenicline tablets (following the manufacturer's dosing regimen). Both groups receive brief stop-smoking advice from the prescribing doctor and withdrawal-orientated behavioural support via community-based stop-smoking counselling services (frequency, duration and mode of delivery tailored for participants) or a research assistant (six weekly 10-15-minute calls). Participants are advised to reduce their smoking over the first 4 days of treatment, with day 5 as their designated quit-date.

Measurements: The primary outcome is carbon monoxide-verified continuous abstinence at 6 months post-quit date. Secondary outcomes at 1, 3, 6 and 12 months post-quit date include: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance, treatment acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life.

Comments: This trial compares cytisine and varenicline when used by the indigenous people of NZ and their extended family for smoking cessation.

Keywords: Cytisine; effectiveness; indigenous; non-inferiority; randomized; safety trial; varenicline.

© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

References

    1. Statistics New Zealand . 2013 census. Wellington: Statistics New Zealand; 2014. Available at: (accessed 26 March 2018) (Archived at on 19 October 2018).
    1. Ministry of Health . Annual Update of Key Results 2016/17: New Zealand Health Survey. Wellington: New Zealand Ministry of Health; 2017.
    1. Blakely T., Fawcett J., Hunt D., Wilson N. What is the contribution of smoking and socioeconomic position to ethnic inequalities in mortality in New Zealand? Lancet 2006; 368: 44–52.
    1. Blakely T., Carter K., Wilson N., Edwards R., Woodward A., Thomson G. et al If nobody smoked tobacco in New Zealand from 2020 onwards, what effect would this have on ethnic inequalities in life expectancy? NZ Med J 2010; 123.
    1. Ministry of Health . The New Zealand Guidelines for Helping People to Stop Smoking. Wellington: Ministry of Health; 2014. Available at: (accessed 19 October 2018) (Archived at on 19 October 2018).
    1. Cahill K., Lindson‐Hawley N., Thomas K., Fanshawe T., Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2016; Issue 5. Art. No.: CD006103. 10.1002/14651858.CD006103.pub7.
    1. Prochaska J., Das S., Benowitz N. Cytisine, the world's oldest smoking cessation aid. BMJ 2013; 347: f5198.
    1. Webb C. Checklist of dicotyledons naturalised in New Zealand. NZ J Botany 1980; 18: 463–472.
    1. Godley E. Introducing Kowhai. Styx report. Landcare Research: Christchurch; 2006.
    1. Coe J. W., Brooks P. R., Vetelino M. G., Wirtz M. C., Arnold E. P., Huang J. et al Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 2005; 48: 3474–3477.
    1. Tutka P., Zatonski W. Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy. Pharmacol Rep 2006; 58: 777–798.
    1. Jeong S.‐H., Newcombe D., Sheridan J., Tingle M. Pharmacokinetics of cytisine, an α4β2 nicotinic receptor partial agonist, in healthy smokers following a single dose. Drug Test Anal 2015; 7: 475–482.
    1. Obach R., Reed‐Hagen A., Krueger S., Obach B., O'Connell T., Zandi K. et al Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro . Drug Meta Disp 2006; 34: 121–130.
    1. Etter J. F. Cytisine for smoking cessation: a literature review and a meta‐analysis. Arch Intern Med 2006; 166: 1553–1559.
    1. McRobbie H., Hajek P., Bullen C., Feigen V. Rapid review of non‐NHS treatments for smoking cessation. London: National Institute of Clinical Excellence; 2006.
    1. Hajek P., McRobbie H., Myers K. Efficacy of cytisine in helping smokers to quit: systematic review and meta analysis. Thorax 2013; 68: 1037–1042.
    1. Walker N., Howe C., Glover M., McRobbie H., Barnes J., Nosa V. et al Randomized comparison of cytisine versus nicotine for smoking cessation. N Engl J Med 2014; 371: 2353–2362.
    1. Aubin H.‐J., Bobak A., Britton J., Oncken C., Billing C., Gong J. et al Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open‐label trial. Thorax 2008; 63: 717–724.
    1. Stapleton J. The case for licensing cytisine now for smoking cessation is overwelming [Letter]. BMJ 2013; 347: f5736.
    1. Leaviss J., Sullivan W., Ren S., Everson‐Hock E., Stevenson M., Stevens J. et al What is the clinical effectiveness and cost‐effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation. Health Tech Assess 2014; 18: 1–119.
    1. Anraad C., Cheung K., Hiligsmann M., Coyle K., Coyle D., Owen L. et al Assessment of cost‐effective changes to the current and potential provision of smoking cessation services: An analysis based on the EQUIPTMOD. Addiction 2018; 10.1111/add.14093.
    1. Thomas D., Farrell M., McRobbie H., Tutka P., Petrie D., West R. et al The effectiveness, safety and cost‐effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: A study protocol for a randomised controlled non‐inferiority trial. Addiction 2018; in press.
    1. Manatū Taonga Ministry for Culture and Heritage . TEARA: The encyclopedia of New Zealand: Whānau—Māori and family. Wellington: Manatū Taonga Ministry for Culture and Heritage; 2018. Available at: (accessed 19 October 2018) (Archived at on 19 October 2018).
    1. Ministry of Health . Population of Lakes DHB. Wellington: Ministry of Health; 2017. Available at: (accessed 19 October 2018) (Archived at on 19 October 2018).
    1. Ministry of Health . Application for subsidy by special authority. Wellington: Ministry of Health; 2017. Available at: (accessed 19 October 2018) (Archived at on 19 October 2018).
    1. Tutka P., Mroz M., Bednarski J., Styk A., Ognik J., Mosierwucz J. et al Cytisine inhibits the anticonvulsant activity of phenytoin and lamotrigine in mice. Pharmacol Rep 2013; 85: 195–200.
    1. Tutka P., Kondrat‐Wróbel M., Zaluska K., Żólkowska D., Florek‐Luszczki M., Luszczki J. Cytisine inhibits the protective activity of various classical and novel antiepileptic drugs against 6 Hz‐induced psychomotor seizures in mice. Psychopharmacology 2017; 234: 281–291.
    1. van Rossem C., Spigt M., Viechtbauer W., Lucas A., van Schayck O. C. P., Kotz D. Effectiveness of intensive practice nurse counselling versus brief general practitioner advice, both combined with varenicline, for smoking cessation: a randomized pragmatic trial in primary care. Addiction 2017; 112: 2237–2247.
    1. Heatherton T. F., Kozlowski L. T., Frecker R. C., Fagerström K. O. The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. Br J Addict 1991; 86: 1119–1127.
    1. Fagerström K. Determinants of Tobacco Use and Renaming the FTND to the Fagerström Test for Cigarette Dependence. Nicotine Tob Res 2012; 14: 75–78.
    1. Bush K., Kivlahan D., McDonell M., Fihn S., Bradley K. The AUDIT alcohol consumption questions (AUDIT‐C): an effective brief screening test for problem drinkers. Arch Intern Med 1998; 158: 1789–1795.
    1. West R., Hajek P. Evaluation of the mood and physical symptoms scale (MPSS) to assess cigarette withdrawal. Psychopharmacology 2004; 177: 195–199.
    1. Devlin N. J., Hansen P., Kind P., Williams A. Logical inconsistencies in survey respondents’ health state valuations—a methodological challenge for estimating social tariffs. Health Econ 2003; 12: 529–544.
    1. Pharmaceutical Management Agency of New Zealand (PHARMAC) PHARMAC's updated guidelines for cost‐utility analyses, with new QALYs per $1M metric. NZ Med J 2012; 125: 89–90.
    1. West R., Hajek P., Stead L., Stapleton J. Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction 2005; 100: 299–303.
    1. Härmark L., van Puijenbroek E., van Grootheest K. Longitudinal monitoring of the safety of drugs by using a web‐based system: the case of pregabalin. Pharmacoepidemiol Drug Safety 2011; 20: 591–597.
    1. Harmark L. Web‐based intensive monitoring. A patient‐based pharmacovigilance tool [PhD thesis]. Groningen, the Netherlands, Rijksuniversiteit Groningen, 2012.
    1. Wiens B. Choosing an equivalence limit for noninferiority and equivalence studies. Control Clin Trials 2002; 23: 2–14.
    1. Rigotti N., Pipe A., Benowitz N., Atteaga C., Garza D., Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease. Circulation 2010; 121: 221–229.
    1. Harris P., Taylor R., Thielke R., Payne J., Gonzalez N., Conde J. Research electronic data capture (REDCap)—a metadata‐driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377–381.
    1. Bates D., Chambers J., Dalgaard P., Gentleman R., Hornik K., Ihaka R. et al The R Project for Statistical Computing; 1997. Available at: (accessed 19 October 2018) (Archived at on 19 October 2018).
    1. Piaggio G., Elbourne D. R., Altman D. G., Pocock S. J., Evans S. J. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 2006; 295: 1152–1160.
    1. D'Agostino R. B. Sr., Massaro J. M., Sullivan L. M. Non‐inferiority trials: design concepts and issues—the encounters of academic consultants in statistics. Stat Med 2003; 22: 169–186.
    1. Drummond M. Methods for the Economic Evaluation of Health Care Programmes, 3rd edn Oxford Medical Publications. Oxford/New York: Oxford University Press; 2005.
    1. Annemans L., Nackaerts K., Bartsch P., Prignot J., Marbaix S. Cost effectiveness of varenicline in Belgium, compared with bupropion, nicotine replacement therapy, brief counselling and unaided smoking cessation: a BENESCO Markov cost‐effectiveness analysis. Clin Drug Invest 2009; 29: 655–665.
    1. Howard P., Knight C., Boler A., Baker C. Cost–utility analysis of varenicline versus existing smoking cessation strategies using the BENESCO simulation model: application to a population of US adult smokers. Pharmacoeconomics 2008; 26: 497–511.
    1. Knight C., Howard P., Baker C. L., Marton J. P. The cost‐effectiveness of an extended course (12+12 weeks) of varenicline compared with other available smoking cessation strategies in the United States: an extension and update to the BENESCO model. Value Health 2010; 13: 209–214.
    1. Briggs A., Sculpher M., Buxton M. Uncertainty in the economic evaluation of health care technologies: the role of sensitivity analysis. Health Econ 1994; 3: 95–104.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren