Ryan J Courtney1, Hayden McRobbie1, Piotr Tutka2, Natasha A Weaver3, Dennis Petrie4, Colin P Mendelsohn5, Anthony Shakeshaft1, Saki Talukder1, Christel Macdonald1, Dennis Thomas6, Benjamin C H Kwan7, Natalie Walker8, Coral Gartner9, Richard P Mattick1, Christine Paul3, Stuart G Ferguson10, Nicholas A Zwar11, Robyn L Richmond12, Christopher M Doran13, Veronica C Boland1, Wayne Hall14, Robert West15, Michael Farrell1. 1. National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia. 2. Department of Experimental and Clinical Pharmacology, University of Rzeszow, Rzeszow, Poland. 3. School of Medicine and Public Health, University of Newcastle, Newcastle, Australia. 4. Centre for Health Economics, Monash Business School, Monash University, Clayton, Australia. 5. No affiliation. 6. Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia. 7. St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia. 8. National Institute for Health Innovation, School of Population Health, University of Auckland, Auckland, New Zealand. 9. School of Public Health, University of Queensland, Herston, Australia. 10. Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Australia. 11. Faculty of Health Sciences and Medicine, Bond University, Robina, Australia. 12. School of Population Health, University of New South Wales, Sydney, Australia. 13. Cluster for Resilience and Wellbeing, Appleton Institute, Central Queensland University, Brisbane, Australia. 14. National Centre for Youth Substance Use Research, University of Queensland, Herston, Australia. 15. Department of Behavioural Science and Health, University College London, London, England.
Abstract
Importance: Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy. Objective: To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation. Design, Setting, and Participants: This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome. Interventions: Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support. Main Outcomes and Measures: The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025. Results: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002). Conclusions and Relevance: Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation. Trial Registration: anzctr.org.au Identifier: ACTRN12616001654448.
Importance: Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy. Objective: To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation. Design, Setting, and Participants: This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome. Interventions: Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support. Main Outcomes and Measures: The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025. Results: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002). Conclusions and Relevance: Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation. Trial Registration: anzctr.org.au Identifier: ACTRN12616001654448.
Authors: Dennis Thomas; Michael Farrell; Hayden McRobbie; Piotr Tutka; Dennis Petrie; Robert West; Mohammad Siahpush; Coral Gartner; Natalie Walker; Colin P Mendelsohn; Wayne Hall; Christine Paul; Nicholas Zwar; Stuart G Ferguson; Veronica C Boland; Robyn Richmond; Christopher M Doran; Anthony Shakeshaft; Richard P Mattick; Ryan J Courtney Journal: Addiction Date: 2019-02-03 Impact factor: 6.526
Authors: Mitchell Nides; Cheryl Oncken; David Gonzales; Stephen Rennard; Eric J Watsky; Rich Anziano; Karen R Reeves Journal: Arch Intern Med Date: 2006 Aug 14-28
Authors: Robert West; Witold Zatonski; Magdalena Cedzynska; Dorota Lewandowska; Joanna Pazik; Paul Aveyard; John Stapleton Journal: N Engl J Med Date: 2011-09-29 Impact factor: 91.245
Authors: Bernard Le Foll; Megan E Piper; Christie D Fowler; Serena Tonstad; Laura Bierut; Lin Lu; Prabhat Jha; Wayne D Hall Journal: Nat Rev Dis Primers Date: 2022-03-24 Impact factor: 52.329
Authors: Bridget C Howard; Hayden McRobbie; Dennis Petrie; Daniel Barker; Colin Mendelsohn; Jack Anderson; Ron Borland; Felix Naughton; Piotr Tutka; Nick Zwar; Veronica C Boland; Alexandra Aiken; Anthony Shakeshaft; Coral Gartner; Robyn L Richmond; Wayne Hall; Richard P Mattick; Michael Farrell; Ryan J Courtney Journal: Trials Date: 2022-09-14 Impact factor: 2.728
Authors: Hilary A Tindle; Matthew S Freiberg; Debbie M Cheng; Natalia Gnatienko; Elena Blokhina; Tatiana Yaroslavtseva; Sally Bendiks; Gregory Patts; Judith Hahn; Kaku So-Armah; Michael D Stein; Kendall Bryant; Dmitry Lioznov; Evgeny Krupitsky; Jeffrey H Samet Journal: JAMA Netw Open Date: 2022-08-01