Evaluation of a Tailored Smoking Cessation Treatment Algorithm Based on Initial Treatment Response and Genotype
Condition: Smoking Cessation
Intervention: Nicotine Patches; Nicotine patches, then bupropion & nicotine patches (Pre-Quit); Nicotine patches, then varenicline (Pre-Quit); Nicotine patches, then nicotine patches (Pre-Quit); Nicotine patches, then bupropion & nicotine patches (Post-Quit); Nicotine patches, then varenicline (Post-Quit); Nicotine patches, then nicotine patches (Post-Quit)
Intervention description: 21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.; 21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.; 21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks); 21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.; 21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.; 21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks); 21mg (1 patch) or 42mg (2 patches) nicotine patches for first seven weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.
Intervention MeSH terms: Bupropion; Nicotine; Varenicline
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 606.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Smoking Cessation; Chantix; varenicline; Nicotine Replacement Therapy; Nicotine Patches; Zyban; bupropion; Quit Smoking

Summary:

      Nicotine replacement therapy (NRT) is a well-tolerated and efficacious smoking cessation
      treatment, and yet many smokers fail to quit using NRT. Many of these smokers may benefit
      from prescription treatment alternatives, including Zyban or Chantix. In this study, the
      investigators propose to develop and evaluate a stepped-care treatment algorithm that would
      evaluate whether smokers who receive treatment with NRT should be supplemented with Zyban or
      switched to Chantix only based on: 1) their initial response to NRT; and 2) individual
      genetic factors found to predict smoking cessation in other studies evaluating these
      treatments. This study is a continuation of our previous studies showing that abstinence
      rates can be increased by starting nicotine patch therapy two weeks before the quit date. The
      investigators will provide pre-cessation NRT to all participants initially. Those who do not
      show a favorable response on early indicators of success (e.g., smoking in the first week
      after the target quit-smoking date) will receive "rescue" treatment by having their NRT
      treatment supplemented with Zyban , by being switched to treatment with Chantix or will
      remain on NRT (control).

      The investigators hypothesize that "Rescue" treatment with Zyban in combination with NRT or
      Chantix will increase success rates over leaving subjects on NRT when they are NRT
      insufficient responders, i.e. they have shown an unfavorable response to NRT in the first
      week pre-quit or the first week post-quit.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18-65 years old

          -  smoked an average of at least 10 cigarettes per day for three cumulative years of a
             brand that delivers (by Federal Trade Commission rated yields) at least 0.5mg nicotine

          -  expired carbon monoxide reading of at least 15ppm

          -  express a desire to quit smoking in the next 30 days

        Exclusion Criteria:

          -  Hypertension (systolic >140 mm Hg, diastolic >100 mm Hg, coupled with a history of
             hypertension); subjects with no previous diagnosis of hypertension may have a
             screening blood pressure up to 160/100.

          -  Hypotension (systolic <90 mm Hg, diastolic <60 mm Hg).

          -  Participants with a history of hypertension may, however, be allowed to participate in
             the study if the study physician or physician assistant determines that the condition
             is stable, controlled by medication, and in no way jeopardizes the individual's
             safety.

          -  Coronary heart disease;

          -  Lifetime history of heart attack;

          -  Cardiac rhythm disorder (irregular heart rhythm);

          -  Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);

          -  Cardiac (heart) disorder (including but not limited to valvular heart disease, heart
             murmur, heart failure);

          -  History of skin allergy;

          -  Active skin disorder (e.g., psoriasis) within the last five years, except minor skin
             conditions (including but not limited to facial acne, minor localized infections, and
             superficial minor wounds);

          -  Liver or kidney disorder (except kidney stones, gallstones);

          -  Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;

          -  Active ulcers in the past 30 days;

          -  Lung disorder (including but not limited to Chronic obstructive pulmonary disease
             (COPD), emphysema, and asthma);

          -  Brain abnormality (including but not limited to stroke, brain tumor, and seizure
             disorder);

          -  History of migraine headaches in the past 5 years;

          -  History of fainting;

          -  Problems giving blood samples;

          -  Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less
             than 180mg/dcl and HbA1c is less than 7%);

          -  Current cancer or treatment for cancer in the past six months (except basal or
             squamous cell skin cancer);

          -  Other major medical condition;

          -  Current psychiatric disease (with the exception of anxiety disorders,
             Obsessive-compulsive disorder (OCD) and ADHD);

          -  Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted
             suicide;

          -  Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be
             used to screen for current (within 2 weeks) depression. Potential subjects who score
             >9 (or who score >0 on item #9 ("Thoughts that you would be better off dead, or of
             hurting yourself in some way") will be excluded from study participation, and, at the
             discretion of the study physician, referred to appropriate psychiatric treatment;

          -  Bulimia or anorexia;

          -  Pregnant or nursing mothers;

          -  Use (within the past 30 days) of:

          -  Illegal drugs (or if the urine drug screen is positive),

          -  Experimental (investigational) drugs;

          -  Psychiatric medications including antidepressants, anti-psychotics or any other
             medications that are known to affect smoking cessation (e.g. clonidine);

          -  Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be
             allowed)

          -  Smokeless tobacco (chewing tobacco, snuff), cigars or pipes;

          -  Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other
             smoking cessation aid.

          -  Alcohol abuse - The AUDIT (Alcohol Use Disorders Identification Test) questionnaire
             will be used to assess alcohol abuse. Potential participants will be asked the first
             two questions on the AUDIT questionnaire during the phone screen. If the person scores
             "4" on both questions, a screening appointment will not be scheduled. During the
             screening session the entire AUDIT questionnaire will be administered. Females who
             score greater than or equal to 13 and males who score greater than or equal to 15 will
             be excluded from the study.

          -  Significant adverse reaction to Wellbutrin / Zyban or Chantix / Varenicline in the
             past