NHLBI-RO1: A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT01553084
• Collaborator: National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 1,086
• Locations: 2
• Arms: 3
• Duration (Months): 63
• Patients Per Site: 543
• Patients Per Site Per Month: 8.6

Study Details

Study Description

Brief Summary

The overall purpose of this research is two-fold. First, the two smoking cessation medication treatments with the strongest evidence of effectiveness have never been directly compared. This research will determine how these two treatments compare in effectiveness in a head-to-head trial, and which types of smokers benefit most from each. Second, much of the data on smoking and health come from studies from many years ago. Today's smokers differ from earlier smokers in many ways that could influence the impact of smoking on health (e.g., weight, sex, diet, socio-economic status); the proposed work will determine how smoking cessation affects cardiovascular and pulmonary health in today's smokers.

Condition or Disease	Intervention/Treatment	Phase
Smoking Cessation; Smoking; Nicotine Dependence	Drug: Varenicline; Drug: Nicotine lozenge; Drug: Nicotine Patch	Phase 4

Detailed Description

The proposed study will recruit and treat a large sample of contemporary smokers and former smokers at an age of increasing health risk, to achieve the following over-arching aims that are important to the NHLBI mission:

• Specific Aim 1: Produce important new data on how to treat smoking optimally by conducting an open label comparative effectiveness trial (CET) that for the first time directly contrasts the two smoking cessation pharmacotherapies with the strongest extant evidence of efficacy: combination NRT and varenicline.

• Specific Aim 2: Determine the impact of smoking cessation on biomarkers and health risk factors, especially those relevant to CVD, in today's smokers, which will elucidate the mechanisms via which cessation benefits health.

• Specific Aim 3: Identify which individuals are at greatest risk for exacerbation of biomarkers or risk factor status due to continued smoking, and who will benefit most from cessation. This will help identify individuals who are most in need of cessation intervention. While all smokers need to quit, this evidence could ultimately be used to help focus treatment and motivate smokers and clinicians to intervene more intensively with patients at greatest risk.

Two secondary aims are to use the results of Primary Aim 1 to develop a treatment assignment algorithm for the optimal treatment of today's smokers and to use the results from Primary Aim 2 to determine the relation of health biomarkers to clinically meaningful disease outcomes such as CVD events.

We will re-recruit as many smoking and non smoking participants from our past longitudinal cohort study("Wisconsin Smokers' Health study"; NCT01122238) in 2004. We will then recruit additional smokers to participate in the comparative effectiveness trial and join the longitudinal cohort..

All participants who enroll will complete questionnaires about their demographics, smoking history, withdrawal symptoms, affect, alcohol use, stressors, medication usage and diet. They will also complete a structured clinical interview to assess mental health. They will provide blood samples for testing of various markers of cardiovascular disease and risk as well as for genetics testing. They will all have carotid ultrasounds, pulmonary function tests, arterial tonometry assessments, and 12-lead ECGs. Participants in Madison will also have a treadmill stress test. Participants will wear a pedometer for 1 week and record the daily number of steps. Participants will provide permission for staff to review their medical charts to assess smoking-relevant diagnoses and treatment. These assessments will occur at baseline and again 3 years later. A smaller subset of these assessments will also be conducted 1 year after enrollment. Participants will also complete brief phone assessments at 6-month intervals up to the 3-year visit.

Interested and eligible smoking participants from the original cohort study and all newly recruited participants will enroll in a new smoking cessation intervention study. Participants in the cessation treatment study will be randomly assigned to receive the nicotine patch, nicotine patch + nicotine lozenge or varenicline. If the participant from the original cohort study is not eligible to use all study medications but is otherwise eligible for cessation treatment, s/he will be assigned to a non-randomized treatment arm and will receive nicotine patch (if appropriate). All cessation participants will receive 6 individual counseling sessions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1086 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Effectiveness of Nicotine patch only	Drug: Nicotine Patch; Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.
Experimental: Effectiveness of Combination NRT	Drug: Nicotine lozenge; Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects.; Drug: Nicotine Patch; Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.
Experimental: Effectiveness of Varenicline [Chantix]	Drug: Varenicline; Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.

Outcome Measures

Primary Outcome Measures

1. Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks [Assessed 26 weeks after the target quit day.]

   Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of <10 ppm..

Secondary Outcome Measures

1. Number of Days to Relapse [Assessed from the target quit day through 26 weeks.]

   The number of days to relapse is defined as the number of days from the target quit day until the first of seven consecutive days of smoking.

2. Number of Participants With Initial Cessation in the First 7 Days Post-quit [Assessed for the first seven days after the target quit date.]

   Defined as at least 1 day of abstinence during the first 7 days after the target quit day.

3. The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT). [Assessed at Baseline and Year 3]

   Change in carotid intima-media thickness (CIMT) from Baseline to Year 3 as a function of smoking status (abstinent versus smoking) at Year 3. Change is calculated as Baseline CIMT score minus Year 3 CIMT score. CIMT score is thickness of the carotid intima-media in millimeters (mm). Lower CIMT values indicate a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

We are only recruiting by invitation only (to members of our past cohort). We will open up enrollment to the public in the Madison, WI and Milwaukee WI areas at the end of 2012.

Inclusion Criteria:

1. To be eligible for the Comparative effectiveness trial, participants must:

• smoke 5 or more cigarettes per day,

• desire to quit smoking but not be currently engaged in cessation treatment,

• be medically eligible to use either combination NRT or varenicline,

• have reliable phone access,

• if female, must not be pregnant and must be willing to use an acceptable birth control method.

Exclusion Criteria:

1. There are no exclusion criteria for participating in the main health outcomes study, other than being unwilling to complete study assessments.

2. All smoking participants from new and original cohorts will be excluded from the cessation trial for the following reasons:

• end-stage renal disease with hemodialysis;

• prior suicide attempts within the last 5 years or current suicidal ideation;

• diagnosis of and/or treatment for schizophrenia;

• other psychotic disorders or bipolar disorder within the last 10 years;

• current PHQ-9 score indicative of moderately severe depression;

• severe untreated hypertension >200/100 mmHg;

• currently taking Wellbutrin, Zyban or bupropion;

• hospitalized for a stroke, heart attack, congestive heart failure or diabetes within the last year;

• used pipe tobacco, cigars, snuff or chew more than twice in the past week.

It should be noted that if any incidental findings appear in any of the cardiology tests (e.g., ultrasound, tonometry, ECG, or exercise stress test; see forms in Supplemental Information section of application), the study cardiologist (Dr. Stein or his designee) will be assign the participant to the non-randomized treatment arm and they will be given the nicotine patch and the same counseling intervention as CET participants. They will not be included in the CET analyses. This will be done to properly address the cardiovascular risk warning from the FDA regarding varenicline (Chantix).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health	Madison	Wisconsin	United States	53711
2	University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health	Milwaukee	Wisconsin	United States	53233

Sponsors and Collaborators

• University of Wisconsin, Madison
• National Institutes of Health (NIH)
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Michael C Fiore, MD, MPH, University of Wisconsin, Madison
• Principal Investigator: James H Stein, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01553084
• Other Study ID Numbers: 1R01HL109031-01; 1R01HL109031-01; 2011-0756
• First Posted: Mar 13, 2012
• Last Update Posted: Sep 2, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by University of Wisconsin, Madison: Smoking Cessation; Smoking; Nicotine
• Additional relevant MeSH terms: Tobacco Use Disorder; Nicotine; Varenicline

Study Results

Participant Flow

Arm/Group Title	Effectiveness of Nicotine Patch Only	Effectiveness of Combination NRT	Effectiveness of Varenicline [Chantix]
Arm/Group Description	Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Nicotine lozenge: Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects. Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Varenicline: Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.
Period Title: Overall Study
STARTED	241	421	424
COMPLETED	226	408	389
NOT COMPLETED	15	13	35

Baseline Characteristics

Arm/Group Title	Effectiveness of Nicotine Patch Only	Effectiveness of Combination NRT	Effectiveness of Varenicline [Chantix]	Total
Arm/Group Description	Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Nicotine lozenge: Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects. Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Varenicline: Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.	Total of all reporting groups
Overall Participants	241	421	424	1086
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.4 (10.9)	47.1 (11.7)	48.5 (11.8)	48.1 (11.6)
Sex: Female, Male (Count of Participants)
Female	125 51.9%	219 52%	222 52.4%	566 52.1%
Male	116 48.1%	202 48%	202 47.6%	520 47.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.8%	3 0.7%	1 0.2%	6 0.6%
Asian	1 0.4%	2 0.5%	0 0%	3 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	72 29.9%	117 27.8%	120 28.3%	309 28.5%
White	158 65.6%	287 68.2%	283 66.7%	728 67%
More than one race	6 2.5%	5 1.2%	11 2.6%	22 2%
Unknown or Not Reported	2 0.8%	7 1.7%	9 2.1%	18 1.7%
Region of Enrollment (participants) [Number]
United States	241 100%	421 100%	424 100%	1086 100%

Outcome Measures

1. Primary Outcome

Title	Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks
Description	Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of <10 ppm..
Time Frame	Assessed 26 weeks after the target quit day.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Effectiveness of Nicotine Patch Only	Effectiveness of Combination NRT	Effectiveness of Varenicline [Chantix]
Arm/Group Description	Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Nicotine lozenge: Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects. Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Varenicline: Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.
Measure Participants	241	421	424
Count of Participants [Participants]	63 26.1%	124 29.5%	108 25.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Effectiveness of Nicotine Patch Only, Effectiveness of Combination NRT
	Comments	Combination NRT will be compared statististically versus Nicotine patch only (the reference or control group).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.3623
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Effectiveness of Nicotine Patch Only, Effectiveness of Varenicline [Chantix]
	Comments	Varenicline will be compared statististically versus Nicotine patch only (the reference or control group).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.1947
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Days to Relapse
Description	The number of days to relapse is defined as the number of days from the target quit day until the first of seven consecutive days of smoking.
Time Frame	Assessed from the target quit day through 26 weeks.

Outcome Measure Data

Analysis Population Description

Participants who did not relapse were censored in the survival analysis.

Arm/Group Title	Effectiveness of Nicotine Patch Only	Effectiveness of Combination NRT	Effectiveness of Varenicline [Chantix]
Arm/Group Description	Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Nicotine lozenge: Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects. Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Varenicline: Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.
Measure Participants	241	421	424
Mean (Standard Deviation) [Days]	29.3 (42.4)	37.4 (46.5)	31.7 (46.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Effectiveness of Nicotine Patch Only, Effectiveness of Combination NRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.3613
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.915
	Confidence Interval	(2-Sided) 95%; .756 to 1.107
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Effectiveness of Nicotine Patch Only, Effectiveness of Varenicline [Chantix]
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.5503
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.943
	Confidence Interval	(2-Sided) 95%; .779 to 1.142
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Initial Cessation in the First 7 Days Post-quit
Description	Defined as at least 1 day of abstinence during the first 7 days after the target quit day.
Time Frame	Assessed for the first seven days after the target quit date.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Effectiveness of Nicotine Patch Only	Effectiveness of Combination NRT	Effectiveness of Varenicline [Chantix]
Arm/Group Description	Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Nicotine lozenge: Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects. Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.	Varenicline: Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.
Measure Participants	241	421	424
Count of Participants [Participants]	176 73%	339 80.5%	289 68.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Effectiveness of Nicotine Patch Only, Effectiveness of Combination NRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.03
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 1.1 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Effectiveness of Nicotine Patch Only, Effectiveness of Varenicline [Chantix]
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.19
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT).
Description	Change in carotid intima-media thickness (CIMT) from Baseline to Year 3 as a function of smoking status (abstinent versus smoking) at Year 3. Change is calculated as Baseline CIMT score minus Year 3 CIMT score. CIMT score is thickness of the carotid intima-media in millimeters (mm). Lower CIMT values indicate a better outcome.
Time Frame	Assessed at Baseline and Year 3

Outcome Measure Data

Analysis Population Description

Includes only participants who completed both Baseline and Year 3 CIMT measurements.

Arm/Group Title	Abstinent at Year 3	Smoking at Year 3
Arm/Group Description	Participants who are abstinent at Year 3 with biochemical confirmation.	Participants who are smoking at Year 3.
Measure Participants	190	522
Mean (Standard Deviation) [millimeters (mm)]	-0.0682 (0.0689)	-0.0620 (0.0755)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Effectiveness of Nicotine Patch Only, Effectiveness of Combination NRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.3282
	Comments
	Method	t-test, 2 sided
	Comments	df=710
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.00612
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.00625
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected for 12 weeks while participants were taking study medication.
Adverse Event Reporting Description	Study participants were asked: "Since your last contact with us, has there been any change in your medical condition or health?" at 1 week prior to the quit smoking visit (quit day), on the quit day, at week 1, week 4, week 8, and week 12. Participants also could self-initiate symptom reports during other visits or phone calls. Information on All-Cause Mortality was not collected.
Arm/Group Title	Effectiveness of Nicotine Patch Only		Effectiveness of Combination NRT		Effectiveness of Varenicline [Chantix]
Arm/Group Description	Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.		Nicotine lozenge: Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects. Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.		Varenicline: Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.
All Cause Mortality
	Effectiveness of Nicotine Patch Only		Effectiveness of Combination NRT		Effectiveness of Varenicline [Chantix]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/241 (2.1%)		6/421 (1.4%)		5/424 (1.2%)
Serious Adverse Events
	Effectiveness of Nicotine Patch Only		Effectiveness of Combination NRT		Effectiveness of Varenicline [Chantix]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/241 (0%)		0/421 (0%)		1/424 (0.2%)
Immune system disorders
Allergic Reaction	0/241 (0%)	0	0/421 (0%)	0	1/424 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Effectiveness of Nicotine Patch Only		Effectiveness of Combination NRT		Effectiveness of Varenicline [Chantix]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	164/241 (68%)		281/421 (66.7%)		353/424 (83.3%)
Cardiac disorders
Heart Symptoms	14/241 (5.8%)	14	13/421 (3.1%)	13	26/424 (6.1%)	26
Gastrointestinal disorders
Nausea	20/241 (8.3%)	20	62/421 (14.7%)	62	121/424 (28.5%)	121
Vomiting	6/241 (2.5%)	6	13/421 (3.1%)	13	22/424 (5.2%)	22
Constipation	5/241 (2.1%)	5	13/421 (3.1%)	13	29/424 (6.8%)	29
Indigestion	4/241 (1.7%)	4	42/421 (10%)	42	22/424 (5.2%)	22
Hiccups	0/241 (0%)	0	26/421 (6.2%)	26	1/424 (0.2%)	1
General disorders
Sleepiness	10/241 (4.1%)	10	26/421 (6.2%)	26	68/424 (16%)	68
Immune system disorders
Itching/hives	53/241 (22%)	53	74/421 (17.6%)	74	7/424 (1.7%)	7
Nervous system disorders
Dizziness	18/241 (7.5%)	18	20/421 (4.8%)	20	27/424 (6.4%)	27
Headache	15/241 (6.2%)	15	28/421 (6.7%)	28	29/424 (6.8%)	29
Product Issues
Mouth Problems	3/241 (1.2%)	3	33/421 (7.8%)	33	7/424 (1.7%)	7
Psychiatric disorders
Vivid Dreams	40/241 (16.6%)	40	55/421 (13.1%)	55	98/424 (23.1%)	98
Insomnia	35/241 (14.5%)	35	45/421 (10.7%)	45	94/424 (22.2%)	94
Depression	10/241 (4.1%)	10	13/421 (3.1%)	13	25/424 (5.9%)	25
Anxious	18/241 (7.5%)	18	26/421 (6.2%)	26	20/424 (4.7%)	20
Agitated/restless	15/241 (6.2%)	15	14/421 (3.3%)	14	35/424 (8.3%)	35
Hostile/angry	7/241 (2.9%)	7	11/421 (2.6%)	11	23/424 (5.4%)	23
Skin and subcutaneous tissue disorders
Rash	27/241 (11.2%)	27	48/421 (11.4%)	48	9/424 (2.1%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.