Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation ® Varenicline for Gradual Versus Abrupt Smoking Cessation in Poorly Motivated Smokers With COPD: A Prematurely Terminated Randomized Controlled Trial

Background: Although smoking is the leading cause of chronic obstructive pulmonary disease (COPD), many patients with COPD smoke, highlighting the need for effective smoking cessation interventions in this population. This study examined the efficacy and safety of varenicline in increasing smoking cessation rates through “gradual” versus “abrupt” cessation in COPD patients with low motivation to quit smoking. Methods: A randomized, open label, 30 - week, controlled trial (ClinicalTrials.gov identifier: NCT02894957) was conducted between January 2019 and October 2020 at a center in Israel. Smokers with COPD, poorly motivated to quit, were randomized to 6 weeks of varenicline for smoking reduction and a target quit day (TQD) at the end of week 6 (gradual cessation group) or ad libitum smoking for 5 weeks, 1 week of varenicline, and a TQD at the end of week 6 (abrupt cessation group). After the pre - quit phase, both groups received 12 - week regular varenicline treatment and 12 - week follow - up. Primary outcome was biochemically - validated continuous abstinence for weeks 6–30. Secondary outcomes were: (1) biochemically - confirmed 7 - day point prevalence abstinence for weeks 4–30, (2) efficient smoking reduction (≥50% in number of cigarettes/day) in the pre - quit phase; and (3) number of cigarettes/day, motivation to quit, and changes in respiratory symptoms and spirometry from baseline through week