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

Abstract

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 six months. Participants were randomized to either reduced nicotine content (RNC) study cigarettes tapered every three 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) versus UNC (n = 123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99 to 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 successfully transitioned to very low nicotine content cigarettes exclusively and substantially reduced their exposure to nicotine.

Figure 1.

Study flow diagram. RNC = reduced nicotine content; UNC = usual nicotine content Due to limited availability of SPECTRUM UNC menthol cigarettes, 51 menthol smokers used comparable nicotine level SPECTRUM menthol cigarettes during Usual Nicotine Content Baseline and continued using this dose if they were randomized to the UNC group. Nicotine contents are based on an estimated 0.7 g tobacco content per cigarette and nicotine concentrations (mg/g) from Richter et al.

Figure 2.

CONSORT diagram. ^a31 (n = 16 RNC group; n = 15 UNC group) participants were limited to choices of returning to own brand or making a quit attempt due to limited study cigarette inventory. ^bPersonal reasons include schedule/transportation issues (n = 9), self-reported quit or active quit attempt (n = 3), or unrelated health issues (n = 3). ^cPer protocol reasons include pregnancy (n = 1), participant behavior (n = 1), or PI decision to withdraw (n = 2).

Figure 3.

Kaplan–Meier curves. Graph shows Kaplan–Meier curves plotted by cigarette group strata, with corresponding confidence bands. The table below the plot identifies the number remaining in the randomized phase by cigarette group in three week increments. Vertical bars on the curves represent censoring, where participants completed the randomized phase of the study (Visit 9).

Figure 4.

Cigarettes per day and exposure biomarkers. CO = Carbon Monoxide; PPM = parts per million; CPD = cigarettes per day. Graphs show means and standard errors of observed data. Visit 2 represents usual brand cigarettes and Visit 3 represents Usual Nicotine Content (UNC) cigarettes (11.6 mg/cigarette). UNC group received UNC cigarettes through Visit 9. Reduced Nicotine Content group received 7.4 mg/cigarette (Visit 3), 3.3 mg/cigarette (Visit 4), 1.4 mg/cigarette (Visit 5), 0.7 mg/cigarette (Visit 6), 0.2 mg/cigarette (Visit 7 and 8). Total CPD summarizes both study and non-study cigarettes. One outlier participant from the UNC group was removed in both CPD figures.