Nicotine & Tobacco Research, Volume 16, Number 11 (November 2014) 1495–1502
Original Investigation
Safety of Varenicline Tartrate and Counseling Versus Counseling Alone for Smoking Cessation: A Randomized Controlled Trial for Inpatients (STOP Study) Kristin Veronica Carson Dip Lab Med1,2, Brian James Smith PhD, FRACP, MBBS1,2, Malcolm Philip Brinn BHSci1,2, Matthew J. Peters FRACP, MBBS3, Robert Fitridge FRACP, MBBS4, Simon A. Koblar FRACP, MBBS5, Jim Jannes PhD, FRACP, MBBS5,6, Kuljit Singh MBBS7, Antony J. Veale PhD, FRACP, MBBS1,2, Sharon Goldsworthy BPharm8, John Litt FRACP, MBBS9, David Edwards BEd10, Khin Moe Hnin MBBS2, Adrian Jeffrey Esterman PhD11
Corresponding Author: Kristin Veronica Carson, Dip Lab Med, Clinical Practice Unit, Basil Hetzel Institute for Translational Health Research, Queen Elizabeth Hospital, DX 465154, 28 Woodville Road, Woodville South, SA 5011, Australia. Telephone: 08-8222-8685; Fax: 08-8222-7872; E-mail: [email protected] Received February 20, 2014; accepted June 4, 2014
Abstract Introduction: Inpatient medical settings offer an opportunistic environment for initiating smoking cessation interventions to patients reflecting on their health. Current evidence has shown the superior efficacy of varenicline tartrate (VT) for smoking cessation compared with other tobacco cessation therapies; however, recent evidence also has highlighted concerns about the safety and tolerability of VT. Given these apprehensions, we aimed to evaluate the safety and effectiveness of VT plus quitlinecounseling compared to quitline-counseling alone in the inpatient medical setting. Methods: Adult patients (n = 392, 20–75 years) admitted with a smoking-related illnesses to 3 hospitals were randomized to receive either 12 weeks of varenicline tartrate (titrated from 0.5 mg daily to 1 mg twice daily) plus quitline-counseling (VT+C), (n = 196) or quitline-counseling alone (n = 196). Results: VT was well tolerated in the inpatient setting among subjects admitted with acute smoking-related illnesses (mean age 52.8 ± 2.89 and 53.7 ± 2.77 years in the VT+C and counseling alone groups, respectively). The most common self-reported adverse event during the 12-week treatment phase was nausea (16.3% in the VT+C group compared with 1.5% in the counseling alone group). Thirteen deaths occurred during the study period (n = 6 were in the VT+C arm compared with n = 7 in the counseling alone arm). All of these subjects had known comorbidities or developed underlying comorbidities. Conclusions: VT appears to be a safe and well-tolerated opportunistic treatment for inpatient smokers who have related chronic disease. Based on the proven efficacy of varenicline from outpatient studies and our recent inpatient evidence, we suggest it be considered as part of standard care in the hospital setting.
Introduction Smoking accounts for 15% of all deaths, 80% of all lung cancer deaths and is responsible for the greatest disease burden in Australia (Australian Bureau of Statistics, 2006; Begg et al., 2007). Varenicline tartrate (VT) is the first smoking cessation
product that acts at the α4β2 nicotinic receptor, being the same brain receptor targeted by nicotine inhaled from smoke (Peters, 2008). Unlike nicotine replacement therapy, it has a dual action. Through its partial nicotinic acetylcholine receptor agonist activity, it both eases cravings and blunts smoking-associated reward or pleasure (Franklin et al., 2011). It has a longer half-life of effect
doi:10.1093/ntr/ntu112 Advance Access publication July 16, 2014 © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: [email protected].
1495
Downloaded from http://ntr.oxfordjournals.org/ at Cornell University Library on June 24, 2015
1Clinical Practice Unit, Basil Hetzel Research Institute, Adelaide, South Australia, Australia; 2Respiratory Medicine, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 3Thoracic Medicine, Concord Repatriation General Hospital, Sydney, New South Wales, Australia; 4Division of Surgery, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 5Stroke Research Programme, University of Adelaide, Adelaide, South Australia, Australia; 6Stroke Unit, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 7Cardiolgoy Department, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 8Pharmacy, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 9Discipline of General Practice, Flinders University, Adelaide, South Australia, Australia; 10Cancer Council of South Australia, Adelaide, South Australia, Australia; 11University of South Australia, Adelaide, South Australia, Australia
STOP trial
Methods Study Design This study was an open-label randomized, multicenter controlled clinical trial, with a 12-week treatment phase. Ethical approval was granted from the respective hospital ethics committees and complied with the ethical principles of the Declaration of Helsinki. All subjects provided written informed consent prior to any procedures. Amendments to the patient information sheet occurred during the study period following the release of new information concerning patients with neuropsychiatric symptoms or a history of cardiovascular disease. All baseline data was collected at the patient’s bedside via interview with followup collection over the phone. Data were stored electronically in a password protected database and in hard copy in a lockable filing cabinet. During the 12-week treatment phase attempts were made to contact all subjects at 3 and 5 days post enrolment, 1, 2, 3, and 4 weeks as well as at the 12-week treatment conclusion for safety and tolerability purposes. Subjects were followed for a total of 52 weeks post enrolment, with additional phone contacts by a project officer at 26 and 52 weeks for collection of efficacy and safety data. Participants and investigators were not blinded to treatment assignment. Different project officers from the initial one recruiting the patient face-to-face completed follow-up assessments. Study Population The study took place at Queen Elizabeth Hospital, Lyell McEwin Hospital, and Royal Adelaide Hospital from August 2008 until December 2011 (including the 52-week follow-up).
1496
Participants were recruited following admission to hospital due to a serious tobacco-related illness episode [as defined by the Centre of Disease Control (Centers for Disease Control and Prevention, 2004)], within the disciplines of respiratory, cardiology, neurology, and vascular medicine. All subjects were motivated to stop smoking and signed a contract to commit to a serious smoking cessation attempt. Inclusion criteria required that they be aged 18–75 years, smoked at least 10 cigarettes on average per day over the past 12 months with a plan of discharge to go home. Participants were excluded if they had cancer within the past 7 years; renal impairment with creatinine clearance
Original Investigation
Safety of Varenicline Tartrate and Counseling Versus Counseling Alone for Smoking Cessation: A Randomized Controlled Trial for Inpatients (STOP Study) Kristin Veronica Carson Dip Lab Med1,2, Brian James Smith PhD, FRACP, MBBS1,2, Malcolm Philip Brinn BHSci1,2, Matthew J. Peters FRACP, MBBS3, Robert Fitridge FRACP, MBBS4, Simon A. Koblar FRACP, MBBS5, Jim Jannes PhD, FRACP, MBBS5,6, Kuljit Singh MBBS7, Antony J. Veale PhD, FRACP, MBBS1,2, Sharon Goldsworthy BPharm8, John Litt FRACP, MBBS9, David Edwards BEd10, Khin Moe Hnin MBBS2, Adrian Jeffrey Esterman PhD11
Corresponding Author: Kristin Veronica Carson, Dip Lab Med, Clinical Practice Unit, Basil Hetzel Institute for Translational Health Research, Queen Elizabeth Hospital, DX 465154, 28 Woodville Road, Woodville South, SA 5011, Australia. Telephone: 08-8222-8685; Fax: 08-8222-7872; E-mail: [email protected] Received February 20, 2014; accepted June 4, 2014
Abstract Introduction: Inpatient medical settings offer an opportunistic environment for initiating smoking cessation interventions to patients reflecting on their health. Current evidence has shown the superior efficacy of varenicline tartrate (VT) for smoking cessation compared with other tobacco cessation therapies; however, recent evidence also has highlighted concerns about the safety and tolerability of VT. Given these apprehensions, we aimed to evaluate the safety and effectiveness of VT plus quitlinecounseling compared to quitline-counseling alone in the inpatient medical setting. Methods: Adult patients (n = 392, 20–75 years) admitted with a smoking-related illnesses to 3 hospitals were randomized to receive either 12 weeks of varenicline tartrate (titrated from 0.5 mg daily to 1 mg twice daily) plus quitline-counseling (VT+C), (n = 196) or quitline-counseling alone (n = 196). Results: VT was well tolerated in the inpatient setting among subjects admitted with acute smoking-related illnesses (mean age 52.8 ± 2.89 and 53.7 ± 2.77 years in the VT+C and counseling alone groups, respectively). The most common self-reported adverse event during the 12-week treatment phase was nausea (16.3% in the VT+C group compared with 1.5% in the counseling alone group). Thirteen deaths occurred during the study period (n = 6 were in the VT+C arm compared with n = 7 in the counseling alone arm). All of these subjects had known comorbidities or developed underlying comorbidities. Conclusions: VT appears to be a safe and well-tolerated opportunistic treatment for inpatient smokers who have related chronic disease. Based on the proven efficacy of varenicline from outpatient studies and our recent inpatient evidence, we suggest it be considered as part of standard care in the hospital setting.
Introduction Smoking accounts for 15% of all deaths, 80% of all lung cancer deaths and is responsible for the greatest disease burden in Australia (Australian Bureau of Statistics, 2006; Begg et al., 2007). Varenicline tartrate (VT) is the first smoking cessation
product that acts at the α4β2 nicotinic receptor, being the same brain receptor targeted by nicotine inhaled from smoke (Peters, 2008). Unlike nicotine replacement therapy, it has a dual action. Through its partial nicotinic acetylcholine receptor agonist activity, it both eases cravings and blunts smoking-associated reward or pleasure (Franklin et al., 2011). It has a longer half-life of effect
doi:10.1093/ntr/ntu112 Advance Access publication July 16, 2014 © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: [email protected].
1495
Downloaded from http://ntr.oxfordjournals.org/ at Cornell University Library on June 24, 2015
1Clinical Practice Unit, Basil Hetzel Research Institute, Adelaide, South Australia, Australia; 2Respiratory Medicine, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 3Thoracic Medicine, Concord Repatriation General Hospital, Sydney, New South Wales, Australia; 4Division of Surgery, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 5Stroke Research Programme, University of Adelaide, Adelaide, South Australia, Australia; 6Stroke Unit, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 7Cardiolgoy Department, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 8Pharmacy, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 9Discipline of General Practice, Flinders University, Adelaide, South Australia, Australia; 10Cancer Council of South Australia, Adelaide, South Australia, Australia; 11University of South Australia, Adelaide, South Australia, Australia
STOP trial
Methods Study Design This study was an open-label randomized, multicenter controlled clinical trial, with a 12-week treatment phase. Ethical approval was granted from the respective hospital ethics committees and complied with the ethical principles of the Declaration of Helsinki. All subjects provided written informed consent prior to any procedures. Amendments to the patient information sheet occurred during the study period following the release of new information concerning patients with neuropsychiatric symptoms or a history of cardiovascular disease. All baseline data was collected at the patient’s bedside via interview with followup collection over the phone. Data were stored electronically in a password protected database and in hard copy in a lockable filing cabinet. During the 12-week treatment phase attempts were made to contact all subjects at 3 and 5 days post enrolment, 1, 2, 3, and 4 weeks as well as at the 12-week treatment conclusion for safety and tolerability purposes. Subjects were followed for a total of 52 weeks post enrolment, with additional phone contacts by a project officer at 26 and 52 weeks for collection of efficacy and safety data. Participants and investigators were not blinded to treatment assignment. Different project officers from the initial one recruiting the patient face-to-face completed follow-up assessments. Study Population The study took place at Queen Elizabeth Hospital, Lyell McEwin Hospital, and Royal Adelaide Hospital from August 2008 until December 2011 (including the 52-week follow-up).
1496
Participants were recruited following admission to hospital due to a serious tobacco-related illness episode [as defined by the Centre of Disease Control (Centers for Disease Control and Prevention, 2004)], within the disciplines of respiratory, cardiology, neurology, and vascular medicine. All subjects were motivated to stop smoking and signed a contract to commit to a serious smoking cessation attempt. Inclusion criteria required that they be aged 18–75 years, smoked at least 10 cigarettes on average per day over the past 12 months with a plan of discharge to go home. Participants were excluded if they had cancer within the past 7 years; renal impairment with creatinine clearance
