Varenicline and Nicotine Replacement Therapy for Smokers Admitted to Hospitals: A Randomized Clinical Trial.

Importance: Varenicline is the most effective sole pharmacotherapy for smoking cessation. If used in combination with nicotine replacement therapy (NRT), cessation rates may be further improved, but the efficacy and safety of the combination need to be evaluated. Objective: To examine whether hospitalized smokers treated with varenicline and NRT lozenges achieve higher prolonged smoking abstinence rates compared with those treated with varenicline alone. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted in adult medical or surgical inpatients of 5 Australian public hospitals with a history of smoking 10 cigarettes or more per day, interested in quitting, and available for 12-month follow-up between May 1, 2019, and May 1, 2021 (final 12-month data collection in May 2022). Data analysis was performed from June 1 to August 30, 2023. Interventions: A 12-week varenicline regimen was initiated during hospitalization at standard doses in all participants. Participants were randomized to additionally use NRT (2 mg) or placebo lozenges if there was an urge to smoke. Behavioral support (Quitline) was offered to all participants. Main Outcomes and Measures: The primary outcome was biochemically verified sustained abstinence at 6 months. Secondary outcomes included self-reported prolonged abstinence, 7-day point prevalence abstinence (3, 6, and 12 months), and medicine-related adverse events. Results: A total of 320 participants (mean [SD] age, 52.5 [12.1] years; 183 [57.2%] male) were randomized. The conduct of biochemical verification was affected by COVID-19 restrictions; consequently, the biochemically verified abstinence in the intervention vs control arms (18 [11.4%] vs 16 [10.1%]; odds ratio [OR], 1.14; 95% CI, 0.56-2.33) did not support the combination therapy. The secondary outcomes in the intervention vs control arms of 7-day point prevalence abstinence at 6 months (54 [34.2%] vs 37 [23.4%]; OR, 1.71; 95% CI, 1.04-2.80), prolonged abstinence at 12 months (47 [29.9%] vs 30 [19.1%]; OR, 1.77; 95% CI, 1.05-3.00), and 7-day point prevalence abstinence at 12-months (48 [30.6%] vs 31 [19.7%]; OR, 1.79; 95% CI, 1.07-2.99) significantly improved with the combination therapy. The self-reported 6-month prolonged abstinence (61 [38.6%] vs 47 [29.7%]; OR, 1.49; 95% CI, 0.93-2.39) favored the combination therapy but was not statistically significant. Medicine-related adverse events were similar in the 2 groups (102 [74.5%] in the intervention group vs 86 [68.3%] in the control group). Conclusions and Relevance: In this randomized clinical trial of the combination of varenicline and NRT lozenges in hospitalized adult daily smokers, the combination treatment improved self-reported abstinence compared with varenicline alone, without compromising safety, but it did not improve biochemically validated abstinence. Trial Registration: anzctr.org.au Identifier: ACTRN12618001792213.

Experiences of hospitalized smokers initiated on varenicline as part of a pragmatic smoking cessation trial.

Varenicline is an effective monotherapy for smoking cessation, but adherence is often suboptimal. This qualitative study explored the experiences of varenicline treatment among participants enrolled in a randomized controlled trial, who self-reported being adherent or nonadherent to varenicline treatment (n = 15). Individual interviews were conducted using a semi-structured interview guide. Data were analyzed using thematic framework approach. An environment of forced abstinence played a key role in motivating quit attempts. The main barriers to varenicline adherence were medicine-related side effects, relapse to smoking, and a belief that the medication was not working if abstinence was not achieved by the target quit date. Participants adherent to treatment adopted a reduce-to-quit approach and noticed a gradual reduction in cigarette cravings. When asked about their preferences for support while on varenicline treatment, participants expressed the need for proactive follow-up by health professionals and more active behavioral support to assist them in adhering to treatment. Prescribers should encourage varenicline users to persist with treatment, even if abstinence is not achieved by the target quit date. Further research is needed to explore the awareness and acceptability of the reduce-to-quit method among prescribers and patients and its impact on varenicline adherence and in term long-term abstinence.

Which smokers enroll in a hospital based smoking cessation trial? Survey of smoking related behaviors, quit attempts, and motivation to quit.

BACKGROUND: Understanding smoking behaviors in hospital patients who smoke may improve inpatient cessation treatments. This study aimed to describe smoking-related behaviors, past-quit attempts, and self-reported difficulties experienced in quitting among those who enrolled in a smoking cessation trial of varenicline. METHODS: Baseline data were obtained from adult hospitalized smokers (average ≥ 10 cigarettes/day in 4-weeks prior to hospitalization) who enrolled in a randomized, placebo-controlled trial of varenicline ± nicotine lozenges at five Australian public hospitals. A logistic regression model tested the association between participant characteristics and quitting in the previous 12 months. RESULTS: Participants' (n = 320; 57% male, 52.5 ± 12.1 years old) motivation and confidence in quitting were high. A total of 120 participants (37.5%) had attempted quitting in the previous 12-months. Prior hospitalization (P = .008) and employment status (P = .015) were significantly associated with past quit attempts. No statistically significant differences were noted in the reason for hospitalization or the level of nicotine dependence between participants who attempted quitting in the previous 12 months and their counterparts. Smoking cessation pharmacotherapy was used by 55% of those attempting to quit; nicotine replacement therapy (65.2%) and varenicline (16.7%) most common. Stress or anxiety, urges to smoke and a lack of motivation were the difficulties experienced in past quit attempts. CONCLUSIONS: Those who had a prior hospitalization and were unemployed had significantly greater odds of reporting past quit attempts. Further research is needed to investigate the degree of adherence among inpatient smokers with the smoke-free hospital policies and the frequency of NRT provision and uptake on admission.

The efficacy and safety of varenicline alone versus in combination with nicotine lozenges for smoking cessation among hospitalised smokers (VANISH): study protocol for a randomised, placebo-controlled trial.

INTRODUCTION: Smoking is a leading cause of premature deaths globally. The health benefits of smoking cessation are many. However, majority of quit attempts are unsuccessful. One way to potentially improve success rates is to evaluate new combinations of existing smoking cessation therapies that may work synergistically to decrease the intensity of withdrawal symptoms and cravings. AIMS: To evaluate the feasibility, efficacy and safety of the combination of varenicline and nicotine replacement therapy (NRT) lozenges versus varenicline alone in assisting hospitalised smokers to quit. METHODS AND ANALYSIS: This is a multicentre, randomised, placebo-controlled trial. Adults with a history of smoking ≥10 cigarettes per day on average in the 4 weeks prior to their hospitalisation will be recruited. Participants will be randomly assigned to either the intervention group and will receive varenicline and NRT lozenges, or the control group and will receive varenicline and placebo lozenges. All participants will be actively referred to behavioural support from telephone Quitline. Participants are followed up at 1 and 3 weeks and 3, 6 and 12 months from the start of treatment. The primary outcome is carbon monoxide validated prolonged abstinence from 2 weeks to 6 months after treatment initiation. Secondary outcomes include self-reported and biochemically validated prolonged and point prevalence abstinence at 3, 6 and 12 months, self-reported adverse events, withdrawal symptoms and cravings, adherence to treatment, Quitline sessions attended and others. According to the Russell Standard, all randomised participants will be accounted for in the primary intention-to-treat analysis. ETHICS AND DISSEMINATION: The trial will be conducted in compliance with the protocol, the principles of Good Clinical Practice, the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (updated 2015) and the Australian Code for the Responsible Conduct of Research (2018). Approval will be sought from the Human Ethics Committees of all the participating hospitals and the university. Written informed consent will be obtained from each participant at the time of recruitment. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry (ACTRN12618001792213).

Factors associated with nicotine replacement therapy use among hospitalised smokers.

INTRODUCTION AND AIMS: Nicotine replacement therapy (NRT) is recommended as a smoking cessation aid for hospitalised smokers. We examined factors associated with NRT use during hospitalisation and after discharge, and NRT uptake when systematically offered free of cost. DESIGN AND METHODS: A nested analysis was conducted using data from a clinical trial that evaluated the effectiveness of a pharmacist-led smoking cessation intervention in 600 hospitalised smokers. RESULTS: NRT was used at least once by 285 (48%) participants during hospitalisation and by 287 (48%) participants during the 12 months post-discharge. Heavy smokers and those who expressed interest in using NRT for their next quit attempt at baseline interview were more likely to use NRT during hospitalisation [odds ratio (OR) 1.94, 95% confidence interval (CI) 1.38, 2.74; OR 2.09, 95% CI 1.48, 2.95] and after discharge (OR 1.70, 95% CI 1.20, 2.41; OR 1.97, 95% CI 1.39, 2.79). Those using six or more medications were more likely to use NRT during hospitalisation (OR 1.65, 95% CI 1.05, 2.61). Post-discharge NRT users were more likely to have been initially admitted for a respiratory or cardiac problem (OR 1.51, 95% CI 1.05, 2.18). When NRT was offered free of cost to a subset of patients (n = 300), 157 (52%) used NRT during hospitalisation. Nicotine dependence and interest in using NRT predicted its use (OR 2.26, 95% CI 1.38, 3.70; OR 2.58, 95% CI 1.58, 4.20). DISCUSSION AND CONCLUSIONS: Targeting heavy smokers, those with cardio-respiratory conditions and those interested in using NRT regardless of regimen complexity could improve NRT uptake.

Development and validation of a 21-item challenges to stopping smoking (CSS-21) scale.

OBJECTIVE: Identification of challenges associated with quitting and overcoming them may improve cessation outcomes. This study describes the development and initial validation of a scale for measuring challenges to stopping smoking. METHODS: The item pool was generated from empirical and theoretical literature and existing scales, expert opinion and interviews with smokers and ex-smokers. The questionnaire was administered to smokers and recent quitters who participated in a hospital-based smoking cessation trial. Exploratory factor analysis was performed to identify subscales in the questionnaire. Internal consistency, validity and robustness of the subscales were evaluated. RESULTS: Of a total of 182 participants with a mean age of 55 years (SD 12.8), 128 (70.3%) were current smokers and 54 (29.7%) ex-smokers. Factor analysis of the 21-item questionnaire resulted in a 2-factor solution representing items measuring intrinsic (9 items) and extrinsic (12 items) challenges. This structure was stable in various analyses and the 2 factors accounted for 50.7% of the total variance of the polychoric correlations between the items. Internal consistency (Cronbach's α) coefficients for the intrinsic and extrinsic subscales were 0.86 and 0.82, respectively. Compared with ex-smokers, current smokers had a higher mean score (± SD) for intrinsic (24.0 ± 6.4 vs 20.5 ± 7.4, p=0.002) and extrinsic subscales (22.3 ± 7.5 vs 18.6 ± 6.0, p=0.001). CONCLUSIONS: Initial evaluation suggests that the 21-item challenges to stopping smoking scale is a valid and reliable instrument that can be used in research and clinical settings to assess challenges to stopping smoking.

Quitting experiences and preferences for a future quit attempt: a study among inpatient smokers.

OBJECTIVE: Understanding smokers' quit experiences and their preferences for a future quit attempt may aid in the development of effective cessation treatments. The aims of this study were to measure tobacco use behaviour; previous quit attempts and outcomes; methods used to assist quitting; difficulties experienced during previous attempts; the motives and preferred methods to assist quitting in a future attempt; identify the factors associated with preferences for smoking cessation. DESIGN: Face-to-face interview using a structured questionnaire. SETTING: Inpatient wards of three Australian public hospitals. PARTICIPANTS: Hospitalised smokers enrolled in a smoking cessation trial. RESULTS: Of 600 enrolled patients (42.8% participation rate), 64.3% (n=386) had attempted quitting in the previous 12 months. On a scale of 1 (low) to 10 (high), current motivation to quit smoking was high (median 9; IQR 6.5-10), but confidence was modest (median 5; IQR 3-8). Among 386 participants who reported past quit attempts, 69.9% (n=270) had used at least one cessation aid to assist quitting. Nicotine replacement therapy (NRT) was most commonly stated (222, 57.5%), although the majority had used NRT for <4 weeks. Hypnotherapy was the most common (68, 17.6%) non-pharmacological treatment. Over 80% (n=311) experienced withdrawal symptoms; craving and irritability were commonly reported. Most participants (351, 58.5%) believed medications, especially NRT (322, 53.7%), would assist them to quit in the future. History of previous smoking cessation medication use was the only independent predictor of interest in using medications for a future quit attempt. CONCLUSIONS: The majority of smokers had attempted quitting in the previous 12 months; NRT was a popular cessation treatment, although it was not used as recommended by most. This suggests a need for assistance in the selection and optimal use of cessation aids for hospitalised smokers. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry: ACTRN12612000368831.

A pharmacist-led system-change smoking cessation intervention for smokers admitted to Australian public hospitals (GIVE UP FOR GOOD): study protocol for a randomised controlled trial.

BACKGROUND: Intensive smoking cessation interventions initiated during hospitalisation are effective, but currently not widely available. Strategies are needed to integrate smoking cessation treatment into routine inpatient care. Pharmacist-led interventions for smoking cessation are feasible and efficacious in both ambulatory and community pharmacy settings. However, there is a lack of evidence from large scale studies of the effectiveness of pharmacist guided programs initiated during patient hospitalisation in achieving long-term abstinence. This study aims to evaluate the effectiveness of a pharmacist-led system change intervention initiated during hospitalisation in Australian public hospitals. METHODS/DESIGN: A multi-centre, randomised controlled trial will be conducted with 12 months follow-up. Smokers, 18 years or older, will be recruited from the wards of three Victorian public hospitals. Participants will be randomly assigned to a usual care or intervention group using a computer generated randomisation list. The intervention group will receive at least three smoking cessation support sessions by a trained pharmacist: the first during the hospital stay, the second on or immediately after discharge and the third within one month post-discharge. All smoking cessation medications will be provided free of charge during the hospital stay and for at least one week after discharge. Participants randomised to usual care will receive the current care routinely provided by the hospital. All measurements at baseline, discharge, one, six and 12 months will be performed by a blinded Research Assistant. The primary outcome measures are carbon monoxide validated 7-day point prevalence abstinence at six and 12 months. DISCUSSION: This is the first large scale study to develop and test a pharmacist-led system change intervention program initiated during patient hospitalisation. If successful, the program could be considered for wider implementation across other hospitals. TRIAL REGISTRATION: ACTRN12612000368831.