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An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use.

ABSTRACT: BACKGROUND AND AIMS:Despite the availability of several efficacious smoking cessation treatments, fewer than 25% of smokers who quit remain abstinent 1 year post-treatment. This study aimed to determine if varenicline and bupropion combination treatment would result in higher abstinence rates than varenicline alone. DESIGN:A double-blind, randomized, parallel-group smoking cessation clinical trial in which participants were exposed to 12 weeks of treatment and followed for 12 months. SETTING:Hospital-based out-patient clinic in Texas, USA specializing in cancer prevention. PARTICIPANTS:A total of 385 community smokers (58.44% male) who smoked 1 pack of cigarettes/day [mean = 19.66 cigarettes/day, standard deviation (SD) = 9.45]; had average carbon monoxide (CO) of 26.43 parts per million (SD = 13.74); and were moderately dependent (Fagerström Test for Cigarette Dependence = 4.79; SD = 2.07). INTERVENTIONS AND COMPARATOR:Smokers were randomized in a 3 : 1 (active: Placebo) ratio to 12 weeks of treatment as follows: placebo (n = 56), varenicline (Var; n = 166), and varenicline + bupropion (Combo; n = 163). MEASUREMENTS:A priori primary outcome: prolonged abstinence at 12 months. SECONDARY OUTCOMES:7-day point prevalence abstinence and continuous abstinence; all abstinence measures at end of treatment and 6-month follow-ups. FINDINGS:Intention-to-treat analysis: the Combo group (n = 163) failed to demonstrate superiority to the Var group (n = 166) for prolonged abstinence at 12 months [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.50-1.64], supported by Bayes factor = 0.06. Both the Var (OR = 6.66, 95% CI = 1.61-59.27) and Combo groups (OR = 6.06, 95% CI = 1.45-54.09) demonstrated superiority to the Placebo group (n = 56; score = 8.38, P < 0.016). CONCLUSIONS:The addition of bupropion to varenicline treatment does not appear to increase smoking abstinence rates above that of varenicline alone. The findings support previous research showing a consistently favorable effect of both varenicline and the combination of varenicline and bupropion on smoking cessation compared with placebo.

SUBMITTER: Cinciripini PM

PROVIDER: S-EPMC6196126 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use.

Cinciripini Paul M PM Minnix Jennifer A JA Green Charles E CE Robinson Jason D JD Engelmann Jeffrey M JM Versace Francesco F Wetter David W DW Shete Sanjay S Karam-Hage Maher M

Addiction (Abingdon, England) 20180421

<h4>Background and aims</h4>Despite the availability of several efficacious smoking cessation treatments, fewer than 25% of smokers who quit remain abstinent 1 year post-treatment. This study aimed to determine if varenicline and bupropion combination treatment would result in higher abstinence rates than varenicline alone.<h4>Design</h4>A double-blind, randomized, parallel-group smoking cessation clinical trial in which participants were exposed to 12 weeks of treatment and followed for 12 mont ...[more]

PMID: 29679432

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Project description:This study replicated and extended results of a previous trial, which found that combination varenicline/bupropion treatment increased smoking abstinence in smokers who were male, highly dependent, and who did not respond to prequit nicotine patch treatment with a >50% reduction in expired-air carbon monoxide in the first week.One hundred and twenty-two male nicotine patch nonresponders and 52 responders were identified. Smokers in each group were randomized to receive 12 weeks of varenicline plus bupropion treatment versus varenicline plus placebo. The primary outcome was continuous smoking abstinence at weeks 8-11 after the target quit date.For smokers with a high level of dependence, judged by having a baseline Fagerstrom Test for Nicotine Dependence (FTND) score ? 6 and cigarette consumption ? 20/d, combination varenicline/bupropion treatment increased the abstinence rate relative to varenicline alone: 71.0% versus 43.8% (odds ratio = 3.14; 95% confidence interval = 1.11-8.92, p [one tailed] = .016). In contrast, less dependent smokers did not show a benefit of combination treatment relative to varenicline (abstinence rates of 32.1% vs. 45.6%, respectively); there was a significant interaction of treatment and dependence level. Patch nonresponders tended to benefit the most from combination treatment, which was well tolerated overall.Combination varenicline/bupropion treatment proved significantly more efficacious than varenicline alone among highly dependent male smokers. These results, together with prior studies, support an adaptive treatment paradigm that assigns smoking cessation treatment according to baseline smoker characteristics and initial response to nicotine patch treatment.This study replicated, in a prospective manner, an important and surprising retrospective finding from a previous clinical trial, which showed that a specific subpopulation of smokers benefited substantially from receiving a combination treatment of varenicline plus bupropion, relative to varenicline plus placebo. Specifically, male smokers having high baseline nicotine dependence (FTND score ? 6 and cigarette consumption ? 20/d), showed a marked increase in smoking abstinence rate on combination pharmacotherapy. The present study likewise found an enhancement in end-of-treatment abstinence rate in this subgroup, from 43.8% to 71.0%. The adaptive treatment paradigm, which classifies smokers based on initial dependence level and response to prequit nicotine patch treatment, may be used to identify target populations of smokers whose success can be enhanced by intervening with combination pharmacotherapy before the quit-smoking date.ClinicalTrials.gov identifier: NCT01806779.

Project description:IntroductionSmoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed.MethodsThis partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8-12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy.ResultsAbstinence rates were 42.9% (95% CI: 36-64) in the control group versus 30.4% (95% CI: 23-37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67-80) versus 52% (95% CI: 49-64) at Week 12 (p<0.001), respectively. The strategy of combining drugs after Week 4 increased abstinence rates in both groups and the significant difference between genetic and control groups was maintained.ConclusionsResults show that using these selected genetic markers was inferior to starting treatment with varenicline (control group), which is currently the most effective smoking cessation drug; moreover, the addition of bupropion in cases of varenicline monotherapy failure improves the efficacy rate until the end of treatment.Clinical trial identifierNCT03362099.

Project description:ImportanceGiven the actions of varenicline tartrate and bupropion hydrochloride sustained-release (SR) on neurobiological targets related to affect and reward, it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness.ObjectiveTo assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning.Design and settingPlacebo-controlled randomized clinical trial at a university medical center.ParticipantsIn total, 294 community volunteers who wanted to quit smoking.InterventionsTwelve weeks of varenicline, bupropion SR, or placebo plus intensive smoking cessation counseling (10 sessions, for a total of approximately 240 minutes of counseling).Main outcome measuresProlonged abstinence from smoking and weekly measures of depression, negative affect, and other symptoms of nicotine withdrawal.ResultsSignificant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit, favoring both active medications compared with placebo. At the 6-month postquit follow-up visit, only the varenicline vs placebo comparison remained significant. Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments, while both active medications improved concentration, reduced craving, and decreased negative affect and sadness compared with placebo, while having little effect (increase or decrease) on anxiety and anger. No differences were noted in self-reported rates of neuropsychiatric adverse events.Conclusions and relevanceIn a community sample, varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable (suppressive) effect on symptoms of depression and other affective measures, with no clear unfavorable effect on neuropsychiatric adverse events.Trial registrationclinicaltrials.gov Identifier: NCT00507728.

Project description:BACKGROUND:Varenicline and bupropion are efficacious, prescription-only pharmacotherapies for smoking cessation; however, their real-world impact is limited by prescriber knowledge, affordability, and accessibility. OBJECTIVE:The primary objective of the MATCH (Medication Aids for Tobacco Cessation Health) study was to evaluate the real-world, long-term effectiveness of mailed bupropion and varenicline in a sample of interested smokers with the utilization of Web-based recruitment and follow-up. In addition, the study aims to investigate the genotypic and phenotypic predictors of cessation. METHODS:This is a two-group, parallel block, randomized (1:1) open-label clinical trial. This study will be conducted online with the baseline enrollment through the study's website and follow-up by emails. In addition, medication prescriptions will be filled by the study contract pharmacy and couriered to participants. Individuals who smoke ?10 cigarettes per day and intend to quit within the next 30 days will be recruited through Public Health Units and Tobacco Control Area Networks throughout Ontario by word-of-mouth and the internet. Eligible participants will receive an email with a prescription for 12-week assigned medication and a letter to take to their physician. The recruitment and randomization will continue until 500 participants per arm have received medication. All participants will receive weekly motivational emails during the treatment phase. The primary outcome measure is the smoking status after 6 months, biochemically confirmed by mailed-in salivary cotinine. Follow-ups will be conducted through emails after 4, 8, 12, 26, and 52 weeks of starting the treatment to assess the smoking prevalence and continuous smoking abstinence. In addition, mailed-in saliva samples will be used for genetic and nicotine metabolism analyses. Furthermore, personality characteristics will be assessed using the Big Five Aspect Scales. RESULTS:The project was funded in 2014 and enrollment was completed in January 2017. Data analysis is currently underway. CONCLUSIONS:To the best of our knowledge, this is the first randomized controlled trial to mass distribute prescription medications for smoking cessation. We expect this method to be logistically feasible and cost effective with quit outcomes that are comparable to published clinical trials. TRIAL REGISTRATION:ClinicalTrials.gov NCT02146911; https://clinicaltrials.gov/ct2/show/NCT02146911 (Archived by WebCite at http://www.webcitation.org/72CZ6AvXZ). REGISTERED REPORT IDENTIFIER:RR1-10.2196/10826.

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An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use.

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An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use.

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