Concurrent Bupropion / Varenicline for Smoking Cessation
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Intervention: Varenicline; Bupropion; Nicotine patches; Nicotine Inhaler
Intervention description: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks.; For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive bupropion at a dose of 150mg once per day. Subsequently, the dose will be 150mg twice per day, and will remain at that dose for the remainder of the 12 weeks.; Nicotine Replacement Therapy Groups:
For smokers with high baseline carbon monoxide (CO): 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or
For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks.
Varenicline and varenicline in combination with bupropion groups:
For smokers with high baseline CO: 42 mg/24 h for 1 week
For smokers with low baseline CO: 21 mg/24 h for 1 week; Nicotine inhaler to use as needed after quit date
Intervention MeSH terms: Bupropion; Nicotine; Varenicline
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 702.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Nicotine addiction; Cigarette smoking; Smoking cessation; Zyban; Chantix; Nicotine patches; Nicotrol Inhaler; varenicline; bupropion

Summary:

      This study focuses on the first step in developing an algorithm for maximizing quit-smoking
      success based on an adaptive approach, which changes treatment from the initial nicotine
      replacement therapy (NRT) when that treatment alone may not be sufficient. These NRT
      "non-responders" are switched (in double-blind fashion) before the quit date to receive
      either varenicline alone or varenicline paired with bupropion. Some participants who would
      otherwise have failed at their quit smoking attempt could be "rescued" by switching to
      alternative pharmacotherapies. The proposed study will evaluate the combination treatment
      against varenicline alone in an adaptive trial design
    

Eligibility criteria:

        Inclusion Criteria:

          -  18-65 years old;

          -  smoked an average of at least 10 cigarettes per day for three cumulative years;

          -  have an expired air CO reading assessed at screening of at least 10ppm;

          -  express a desire to quit smoking within 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 with symptoms (systolic <90 mm Hg, diastolic <60 mm Hg).

          -  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;

          -  Currently symptomatic lung disorder/disease (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);

          -  Migraine headaches that occur more frequently than once per week;

          -  Recent, unexplained fainting spells;

          -  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;

          -  Bulimia or anorexia;

          -  Pregnant or nursing mothers;

          -  Alcohol abuse;

          -  Use of Opiate medications for pain or sleep in the past 14 days;

          -  Significant adverse reaction to nicotine patches, nicotine inhalers, bupropion /
             Wellbutrin / Zyban or Chantix / Varenicline in the past.

          -  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);

          -  Smokeless tobacco (chewing tobacco, snuff), cigars, pipes or e-cigarettes;

          -  Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other
             smoking cessation aid.