Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers with Low Socioeconomic Status: A Double-Blind Randomized Clinical Trial.

Introduction The Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-addicting very low nicotine content (VLNC). Methods A 33-week, two-arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next 6 months. Participants were randomized to either Reduced Nicotine Content (RNC) study cigarettes tapered every 3 weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to Usual Nicotine Content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation. Results The RNC (n= 122) vs. UNC (n=123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99-5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference -137 ng/mL; 95% CI -172, -102). The RNC group smoked fewer CPD (-4.1; 95% CI -6.44, -1.75) and had lower carbon monoxide levels (-4.0 ppm; 95% CI -7.7, -0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine= 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N=6/22, 27%). Conclusions This study supports a VLNC standard in cigarettes. Implications Differential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers in the study were able to successfully transition to VLNC cigarettes exclusively and substantially reduced their exposure to nicotine.