Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial
Background: Initiating varenicline use 4 weeks before the target quit date (TQD) reduces smoking in the run-in phase and increases end-treatment cessation rates; however, the lack of a smoke intake plateau suggests longer preloading periods are required. This study assessed whether varenicline prelo...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | EClinicalMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537019302330 |
| _version_ | 1811216230735937536 |
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| author | Abraham Bohadana Yossi Freier-Dror Vardit Peles Polina Babai Gabriel Izbicki |
| author_facet | Abraham Bohadana Yossi Freier-Dror Vardit Peles Polina Babai Gabriel Izbicki |
| author_sort | Abraham Bohadana |
| collection | DOAJ |
| description | Background: Initiating varenicline use 4 weeks before the target quit date (TQD) reduces smoking in the run-in phase and increases end-treatment cessation rates; however, the lack of a smoke intake plateau suggests longer preloading periods are required. This study assessed whether varenicline preloading for 6 weeks reduced pre-quit smoke intake and enhanced 6-month abstinence outcomes compared with the standard 1-week preloading. Methods: In this randomised single-centre controlled trial, (ClinicalTrials.gov identifier: NCT02634281), conducted between February 2016 and July 2018 in Israel, daily smokers (n = 242) aged ≥ 18 years were randomly assigned (1:1) to receive varenicline preloading for 6 weeks (n = 121) or a placebo for 5 weeks followed by varenicline for 1 week (n = 121) before the TQD. Participants and researchers were masked to both group assignment and treatment allocation. Both groups received standard 12-week post-TQD varenicline treatment. The primary outcome was the 24-week biochemically verified continuous abstinence rate (CAR) from weeks 6 (TQD)–30. Secondary outcomes included the 23-week CAR from 1-week post-TQD (week 7) to week 30, and the 7-day point-prevalence (PP) abstinence at week 30. Other measures included pre- and post-quit rewards, smoking urges, nausea, aversion, and markers of cigarette consumption. Findings: By intention-to-treat, the 24-week CAR, weeks 6–30 with extended preloading was significantly higher than with standard preloading (23·1% vs. 4·1%; risk reduction [RR]: -0·19 [95% confidence interval [CI]:-0·10—0·24]; p < 0·001). Extended preloading also showed better secondary outcomes. Extended preloading significantly decreased pre-quit rewards, urges, and smoke intake, including unsolicited smoking abstinence. Post-quit urges remained remarkably lower with extended preloading. Participants receiving extended preloading reported more nausea at week 4 (39.6% vs 11.5%) and abnormal dreams at week 6 (7.7% vs. 0%). Participants receiving standard preloading reported more constipation at week 7 (7.6% vs. 0%) and dizziness at weeks 7 (12.1% vs. 2.5%) and 12 (10.7% vs 1.4%). Interpretation: Extended preloading reduced ad lib smoking, enhanced cessation rates at 3 and 6 months, and decreased pre- and post-quit rewards and smoking drive in a pattern compatible with a reinforcement-reduction mechanism. These data substantiate extending the standard pre-treatment period, and suggest that targeting pre-quit smoking sensations should be a treatment priority, although confirmatory evidence is needed from larger clinical trials. Funding: This study was funded by a 2013 Global Research Award for Nicotine Dependence (GRAND) supported by Pfizer, Inc. (#WI182915). Keywords: Smoking cessation, Smoking reduction, Varenicline, Extended preloading |
| first_indexed | 2024-04-12T06:35:56Z |
| format | Article |
| id | doaj.art-722ef4bea0d24d70a4181248e252bee8 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-04-12T06:35:56Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-722ef4bea0d24d70a4181248e252bee82022-12-22T03:43:53ZengElsevierEClinicalMedicine2589-53702020-02-0119Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trialAbraham Bohadana0Yossi Freier-Dror1Vardit Peles2Polina Babai3Gabriel Izbicki4Respiratory Research Unit, Pulmonary Institute, Shaare Zedek Medical Center, Affiliated with the Hadassah School of Medicine, Hebrew University of Jerusalem, 12 Baiyt Street, Jerusalem 91031, Israel; Corresponding author.Mashav Applied Research, 5 Chail Nashim Street, Jerusalem 9332005, IsraelRespiratory Research Unit, Pulmonary Institute, Shaare Zedek Medical Center, Affiliated with the Hadassah School of Medicine, Hebrew University of Jerusalem, 12 Baiyt Street, Jerusalem 91031, IsraelMashav Applied Research, 5 Chail Nashim Street, Jerusalem 9332005, IsraelRespiratory Research Unit, Pulmonary Institute, Shaare Zedek Medical Center, Affiliated with the Hadassah School of Medicine, Hebrew University of Jerusalem, 12 Baiyt Street, Jerusalem 91031, IsraelBackground: Initiating varenicline use 4 weeks before the target quit date (TQD) reduces smoking in the run-in phase and increases end-treatment cessation rates; however, the lack of a smoke intake plateau suggests longer preloading periods are required. This study assessed whether varenicline preloading for 6 weeks reduced pre-quit smoke intake and enhanced 6-month abstinence outcomes compared with the standard 1-week preloading. Methods: In this randomised single-centre controlled trial, (ClinicalTrials.gov identifier: NCT02634281), conducted between February 2016 and July 2018 in Israel, daily smokers (n = 242) aged ≥ 18 years were randomly assigned (1:1) to receive varenicline preloading for 6 weeks (n = 121) or a placebo for 5 weeks followed by varenicline for 1 week (n = 121) before the TQD. Participants and researchers were masked to both group assignment and treatment allocation. Both groups received standard 12-week post-TQD varenicline treatment. The primary outcome was the 24-week biochemically verified continuous abstinence rate (CAR) from weeks 6 (TQD)–30. Secondary outcomes included the 23-week CAR from 1-week post-TQD (week 7) to week 30, and the 7-day point-prevalence (PP) abstinence at week 30. Other measures included pre- and post-quit rewards, smoking urges, nausea, aversion, and markers of cigarette consumption. Findings: By intention-to-treat, the 24-week CAR, weeks 6–30 with extended preloading was significantly higher than with standard preloading (23·1% vs. 4·1%; risk reduction [RR]: -0·19 [95% confidence interval [CI]:-0·10—0·24]; p < 0·001). Extended preloading also showed better secondary outcomes. Extended preloading significantly decreased pre-quit rewards, urges, and smoke intake, including unsolicited smoking abstinence. Post-quit urges remained remarkably lower with extended preloading. Participants receiving extended preloading reported more nausea at week 4 (39.6% vs 11.5%) and abnormal dreams at week 6 (7.7% vs. 0%). Participants receiving standard preloading reported more constipation at week 7 (7.6% vs. 0%) and dizziness at weeks 7 (12.1% vs. 2.5%) and 12 (10.7% vs 1.4%). Interpretation: Extended preloading reduced ad lib smoking, enhanced cessation rates at 3 and 6 months, and decreased pre- and post-quit rewards and smoking drive in a pattern compatible with a reinforcement-reduction mechanism. These data substantiate extending the standard pre-treatment period, and suggest that targeting pre-quit smoking sensations should be a treatment priority, although confirmatory evidence is needed from larger clinical trials. Funding: This study was funded by a 2013 Global Research Award for Nicotine Dependence (GRAND) supported by Pfizer, Inc. (#WI182915). Keywords: Smoking cessation, Smoking reduction, Varenicline, Extended preloadinghttp://www.sciencedirect.com/science/article/pii/S2589537019302330 |
| spellingShingle | Abraham Bohadana Yossi Freier-Dror Vardit Peles Polina Babai Gabriel Izbicki Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial EClinicalMedicine |
| title | Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial |
| title_full | Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial |
| title_fullStr | Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial |
| title_full_unstemmed | Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial |
| title_short | Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial |
| title_sort | extending varenicline preloading to 6 weeks facilitates smoking cessation a single site randomised controlled trial |
| url | http://www.sciencedirect.com/science/article/pii/S2589537019302330 |
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