Adaptive Pharmacotherapy in Helping Smokers Quit Smoking

PRIMARY OBJECTIVES:

I. To compare 30-day continuous biochemically confirmed abstinence at 12-weeks post-target quit day (TQD) in participants randomized to adaptive pharmacotherapy algorithm versus (vs.) standard-of-care treatment.

SECONDARY OBJECTIVES:

I. To compare 7-day point prevalent biochemically confirmed abstinence rates at 2- and 12-weeks post-TQD in participants randomized to adaptive pharmacotherapy algorithm vs. standard-of-care treatment.

II. To compare phone-based self-reported abstinence at multiple time points (1, 2, 6, 12, 26 and 52 weeks post-TQD) assessed by phone in participants randomized to adaptive pharmacotherapy algorithm vs. standard-of-care treatment.

III. To compare smoking reduction (number of cigarettes per day [cpd]) at 2- and 12-weeks post-TQD and on phone-based self-report at 1, 2, 6, 12, 26 and 52 weeks post-TQD in participants randomized to adaptive pharmacotherapy algorithm vs. standard-of-care treatment.

IV. To assess demographic variables (age, gender, race, education, and income) for an association with all abstinence outcomes and, if significant, will be used as covariates in analysis of all abstinence outcomes.

V. To assess potential baseline (pre-intervention) predictors of abstinence including self-reported dependence, stress, anxiety, depression, alcohol and drug use, and self-efficacy.

VI. To assess change in self-reported measures at baseline (pre-quit) to 2- and 12-weeks post TQD on repeated standardized measures of nicotine dependence, stress, anxiety, depression, and self-efficacy.

VII. To compare baseline scores on anxiety, depression, and stress for their effect on allocation to Responder or Non-Responder in the adaptive and standard treatment.

VIII. To compare phone-assessed non-standardized single item questions on urges, withdrawal, confidence and motivation at 1, 2, 6, 12, 26 and 52 weeks post-TQD.

IX. To conduct a cost-benefit analyses on allocation to adaptive pharmacotherapy algorithm vs. standard-of-care treatment from the perspective of multiple stake holders: smokers, healthcare systems (clinics/hospitals), insurance companies, and employers.

TERTIARY OBJECTIVES:

I. Demographics of patients at Duke Smoking Cessation Program (DSCP) and Duke Center for Smoking Cessation (CSC).

II. Medications used.

III. Attendance at DSCP appointments.

IV. Referral routes to DSCP.

V. Medication side effects.

VI. Medication adherence.

OUTLINE: Patients are randomized to 1 of 4 groups.

GROUP I: Beginning 4 weeks prior to TQD, patients receive varenicline tartrate orally (PO) once in the morning and placebo varenicline tartrate PO once in the evening on days 1-3, varenicline tartrate PO twice daily (BID) on days 4-7 and day 8 until end of treatment (12 weeks post-TQD). At 2 weeks pre-TQD, patients who do not show > 50% reduction in cigarettes-per-day from baseline also receive bupropion hydrochloride PO once in the morning and PO BID on day 4 until end of treatment (12 weeks post-TQD). At 2 weeks pre-TQD, patients who show > 50% reduction in cigarettes per day from baseline also receive placebo bupropion hydrochloride PO once in the morning on days 1-3 and day 4 until end of treatment (12 weeks post-TQD).

GROUP II: Beginning 4 weeks prior to TQD, patients receive placebo varenicline tartrate PO BID. Beginning 1 week prior to TQD, patients receive varenicline tartrate PO once in the morning and placebo varenicline tartrate PO once in the evening on days 1-3, varenicline tartrate PO twice daily (BID) on days 4-7 and day 8 until end of treatment (12 weeks post-TQD). Beginning 1 week prior to TQD, patients also receive placebo bupropion hydrochloride PO once in the morning on days 1-3 and day 4 until end of treatment (12 weeks post-TQD).

GROUP III: Beginning 4 weeks prior to TQD, patients wear nicotine patch daily for 12 weeks post-TQD. At 2 weeks pre-TQD, patients who do not show > 50% reduction in cigarettes-per-day from baseline also receive bupropion hydrochloride PO once in the morning and PO BID on day 4 until end of treatment (12 weeks post-TQD). At 2 weeks pre-TQD, patients who show > 50% reduction in cigarettes per day from baseline also receive placebo bupropion hydrochloride PO once in the morning on days 1-3 and day 4 until end of treatment (12 weeks post-TQD).

GROUP IV: Beginning 4 weeks prior to TQD, patients wear placebo nicotine patch once daily for 12 weeks post-TQD. Beginning 1 week prior to TQD, patients wear nicotine patch once daily for 12 weeks post-TQD. Beginning 1 week prior to TQD, patients also receive placebo bupropion hydrochloride PO once in the morning on days 1-3 and day 4 until end of treatment (12 weeks post-TQD).

After completion of study treatment. participants are followed up at 26 and 52 weeks post-TQD.