Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking

• Sponsor: Fox Chase Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00365508
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 642
• Locations: 10
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 64.2
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

RATIONALE: Stop-smoking plans, including counseling and nicotine replacement therapy, may help smokers quit smoking. It is not yet known whether counseling and the nicotine lozenge is more effective than counseling and the nicotine patch in helping adult smokers quit smoking.

PURPOSE: This randomized phase III trial is studying counseling and the nicotine lozenge to see how well they work compared to counseling and the nicotine patch in helping smokers quit smoking.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer; Cervical Cancer; Esophageal Cancer; Gastric Cancer; Head and Neck Cancer; Kidney Cancer; Leukemia; Liver Cancer; Lung Cancer; Pancreatic Cancer; Tobacco Use Disorder	Drug: nicotine lozenge; Drug: nicotine patch	Phase 4

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of behavioral counseling and nicotine-replacement therapy with either oral nicotine lozenge (NL) or transdermal nicotine patch (NP), in terms of promoting rates of smoking cessation (e.g., continued abstinence), in adult smokers.

• Examine the degree to which nicotine replacement therapy (NRT) preference, desire to control NRT dosing, irregular smoking schedules, and desire for oral preoccupation moderates the relative efficacy of NL vs NP in promoting smoking cessation.

• Evaluate the impact of the NL on mediators of smoking cessation (i.e., reduced craving, diminished withdrawal symptoms, cue reactivity, and increased perceived control over withdrawal symptoms).

Secondary

• Compare the rate of compliance with NRT across the 2 treatment arms and examine if compliance rate mediates the effects of NRT on quit rates.

• Examine the potential role of genes related to nicotine dependence such as genes related to nicotine metabolism enzymes (e.g., CYP1A1) or genes related to dopamine concentrations (e.g., DRD2).

OUTLINE: This is a randomized, open-label, multicenter study. Participants are stratified according to study center. Participants are randomized to 1 of 2 intervention arms.

All participants undergo smoking cessation counseling in weeks 1, 3, 5, 7, and 9. Beginning in week 3, participants are asked to quit smoking for 12 weeks (weeks 3-14).

• Arm I: Participants apply a transdermal nicotine patch at 3 different time periods during weeks 3-14; a higher-dose patch is applied for weeks 3-8, a medium-dose patch is applied for weeks 9-10, and a lower-dose patch is applied for weeks 11-14.

• Arm II: Participants receive one oral nicotine lozenge every 1-2 hours in weeks 3-8 (≥ 9 lozenges per day), one lozenge every 2-4 hours in weeks 9-11 (≥ 5 lozenges per day), and 1 lozenge every 4-8 hours in weeks 12-14 (≥ 3 lozenges per day).

The moderating variables (e.g., nicotine replacement-therapy [NRT] preference and the smoker's desire to control NRT dosing) are assessed at baseline. The mediating variables (i.e., reduced craving, diminished withdrawal symptoms, cue reactivity, and increased perceived control over withdrawal symptoms) are assessed at baseline and then at weeks 5, 7, 9, within weeks 14-16, and within weeks 26-28. Continuous abstinence will be measured at week 27.

PROJECTED ACCRUAL: A total of 700 participants will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 642 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparing the Lozenge to the Patch for Smoking Cessation
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Participants apply a transdermal nicotine patch at 3 different time periods during weeks 3-14; a higher-dose patch is applied for weeks 3-8, a medium-dose patch is applied for weeks 9-10, and a lower-dose patch is applied for weeks 11-14.	Drug: nicotine patch; transdermal nicotine patch; Other Names: transdermal nicotine patch
Experimental: Arm II Participants receive one oral nicotine lozenge every 1-2 hours in weeks 3-8 (≥ 9 lozenges per day), one lozenge every 2-4 hours in weeks 9-11 (≥ 5 lozenges per day), and 1 lozenge every 4-8 hours in weeks 12-14 (≥ 3 lozenges per day).	Drug: nicotine lozenge; nicotine lozenge

Outcome Measures

Primary Outcome Measures

1. 24-hour Point Prevalence Abstinence at the 6-month Follow up [6-months]

Secondary Outcome Measures

1. Rate of Compliance During the First 2 Weeks [2 weeks]

   Applied to use of the intervention (number of lozenges/day or number of patches used per week) not considering abstinence

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Smokes at least 10 cigarettes a day on average for the past year

• No prior diagnosis of cancer (unless completed treatment AND no evidence of disease within the past 5 years)

• Able to use nicotine replacement therapy

PATIENT CHARACTERISTICS:

• Able to communicate in English

• Must reside in the geographic area for ≥ 6 months

• Current asthma, ulcer, or diabetes allowed provided medical clearance from the participant's physician is obtained

• No evidence of drug or alcohol abuse

• No known HIV positivity

• No heart disease, including any of the following:

• Current diagnosis of coronary artery disease

• Abnormal heart rhythm or an arrhythmia

• Heart failure

• Heart valve disease

• Congenital heart disease

• Heart muscle disease or cardiomyopathy

• Pericardial disease

• Aorta disease

• Vascular disease

• Myocardial infarction

• High blood pressure (defined as blood pressure > 140/90 mm Hg) not receiving antihypertensive medication

• History of or current high blood pressure controlled by antihypertensive medication and having medical clearance from physician allowed

• No allergy to adhesive tape or latex

• Not pregnant or nursing

• Negative pregnancy test

• Fertile participants must use effective contraception during and for ≥ 1 month prior to and after completion of study treatment

PRIOR CONCURRENT THERAPY:

• At least 30 days since prior and no concurrent benzodiazepine (e.g., diazepam, alprazolam, or lorazepam)

• At least 6 months since prior antiretroviral medications

• At least 6 months since prior and no concurrent medication for depression (e.g., phenelzine sulfate, pargyline hydrochloride, tranylcypromine sulfate, paroxetine hydrochloride, sertraline hydrochloride, fluoxetine hydrochloride)

• No concurrent antipsychotics (e.g., lithium) or theophylline

• No concurrent substance abuse treatment

• No concurrent bupropion hydrochloride

• No other concurrent pharmacologic aid or any other form of formal assistance for smoking cessation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Howard University Cancer Center	Washington	District of Columbia	United States	20060
2	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
3	Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912-3500
4	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Burlington County	Mount Holly	New Jersey	United States	08060-2099
5	Hematology Oncology Associates of Central New York, PC - Northeast Center	East Syracuse	New York	United States	13057-4510
6	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
7	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
8	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
9	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
10	Nashville General Hospital at Meharry	Nashville	Tennessee	United States	37208

Sponsors and Collaborators

• Fox Chase Cancer Center
• National Cancer Institute (NCI)

Investigators

• Study Chair: Robert A. Schnoll, PhD, Fox Chase Cancer Center - Cheltenham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fox Chase Cancer Center
• ClinicalTrials.gov Identifier: NCT00365508
• Other Study ID Numbers: CDR0000491296; FCCC-FCRB-04-003-P; 05-818
• First Posted: Aug 17, 2006
• Last Update Posted: Mar 29, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Fox Chase Cancer Center: bladder cancer; cervical cancer; esophageal cancer; gastric cancer; renal cell carcinoma; adult primary liver cancer; non-small cell lung cancer; small cell lung cancer; pancreatic cancer; hypopharyngeal cancer; laryngeal cancer; lip and oral cavity cancer; nasopharyngeal cancer; oropharyngeal cancer; paranasal sinus and nasal cavity cancer; adult acute myeloid leukemia; tongue cancer; tobacco use disorder
• Additional relevant MeSH terms: Lung Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Uterine Cervical Neoplasms; Urinary Bladder Neoplasms; Esophageal Neoplasms; Liver Neoplasms; Tobacco Use Disorder; Nicotine

Study Results

Participant Flow

Recruitment Details	Participants were recruited through ads/physician referral at: FCCC, Geisinger Medical Center, Hematology Oncology Associates of Central NY, Howard University, LSU, Main Line Health System, Medical College of GA, Meharry Medical College, Mount Sinai Medical Center (Miami), North Shore University, SUNY Downstate Medical Center, and Virtua Health.
Pre-assignment Detail	1299 individuals were screened for this trial over 4 years; 454 individuals were ineligible, 194 refused enrollment, and 651 were randomized. Nine individuals either withdrew from the study prior to treatment or were found to be ineligible after randomization and were removed from the intent-to-treat sample. The final ITT sample was 642 (321/arm).

Arm/Group Title	Nicotine Patch	Nicotine Lozenge
Arm/Group Description	Participants apply a transdermal nicotine patch at 3 different time periods during weeks 3-14; a higher-dose patch is applied for weeks 3-8, a medium-dose patch is applied for weeks 9-10, and a lower-dose patch is applied for weeks 11-14.	Participants receive one oral nicotine lozenge every 1-2 hours in weeks 3-8 (≥ 9 lozenges per day), one lozenge every 2-4 hours in weeks 9-11 (≥ 5 lozenges per day), and 1 lozenge every 4-8 hours in weeks 12-14 (≥ 3 lozenges per day).
Period Title: Overall Study
STARTED	321	321
COMPLETED	182	167
NOT COMPLETED	139	154

Baseline Characteristics

Arm/Group Title	Arm I	Arm II	Total
Arm/Group Description	Participants apply a transdermal nicotine patch at 3 different time periods during weeks 3-14; a higher-dose patch is applied for weeks 3-8, a medium-dose patch is applied for weeks 9-10, and a lower-dose patch is applied for weeks 11-14.	Participants receive one oral nicotine lozenge every 1-2 hours in weeks 3-8 (≥ 9 lozenges per day), one lozenge every 2-4 hours in weeks 9-11 (≥ 5 lozenges per day), and 1 lozenge every 4-8 hours in weeks 12-14 (≥ 3 lozenges per day).	Total of all reporting groups
Overall Participants	321	321	642
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.7 (12.7)	44.8 (11.9)	44.7 (12.3)
Sex: Female, Male (Count of Participants)
Female	195 60.7%	170 53%	365 56.9%
Male	126 39.3%	151 47%	277 43.1%

Outcome Measures

1. Primary Outcome

Title	24-hour Point Prevalence Abstinence at the 6-month Follow up
Time Frame	6-months

Outcome Measure Data

Analysis Population Description

Intent to treat analysis (lost to follow-up = smoker)

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Participants apply a transdermal nicotine patch at 3 different time periods during weeks 3-14; a higher-dose patch is applied for weeks 3-8, a medium-dose patch is applied for weeks 9-10, and a lower-dose patch is applied for weeks 11-14.	Participants receive one oral nicotine lozenge every 1-2 hours in weeks 3-8 (≥ 9 lozenges per day), one lozenge every 2-4 hours in weeks 9-11 (≥ 5 lozenges per day), and 1 lozenge every 4-8 hours in weeks 12-14 (≥ 3 lozenges per day).
Measure Participants	321	321
Number [participants]	50 15.6%	35 10.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II
	Comments	Chi-square was used to examine the relationship between treatment arm and 24-hour point prevalence abstinence at 6-months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.05
	Comments	a priori threshold for statistical significance
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Rate of Compliance During the First 2 Weeks
Description	Applied to use of the intervention (number of lozenges/day or number of patches used per week) not considering abstinence
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Participants apply a transdermal nicotine patch at 3 different time periods during weeks 3-14; a higher-dose patch is applied for weeks 3-8, a medium-dose patch is applied for weeks 9-10, and a lower-dose patch is applied for weeks 11-14.	Participants receive one oral nicotine lozenge every 1-2 hours in weeks 3-8 (≥ 9 lozenges per day), one lozenge every 2-4 hours in weeks 9-11 (≥ 5 lozenges per day), and 1 lozenge every 4-8 hours in weeks 12-14 (≥ 3 lozenges per day).
Measure Participants	321	321
Number [participants]	231 72%	87 27.1%

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Administered a checklist of side effects from NRT and collected any additional information on adverse events.
Arm/Group Title	Arm I		Arm II
Arm/Group Description	Participants apply a transdermal nicotine patch at 3 different time periods during weeks 3-14; a higher-dose patch is applied for weeks 3-8, a medium-dose patch is applied for weeks 9-10, and a lower-dose patch is applied for weeks 11-14.		Participants receive one oral nicotine lozenge every 1-2 hours in weeks 3-8 (≥ 9 lozenges per day), one lozenge every 2-4 hours in weeks 9-11 (≥ 5 lozenges per day), and 1 lozenge every 4-8 hours in weeks 12-14 (≥ 3 lozenges per day).
All Cause Mortality
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/321 (1.2%)		7/321 (2.2%)
Cardiac disorders
Stroke	2/321 (0.6%)	2	0/321 (0%)	0
Heart disease	0/321 (0%)	0	1/321 (0.3%)	1
heart attack	0/321 (0%)	0	1/321 (0.3%)	1
Gastrointestinal disorders
ulcer	0/321 (0%)	0	1/321 (0.3%)	1
appendicitis	0/321 (0%)	0	1/321 (0.3%)	1
Injury, poisoning and procedural complications
killed in car accident	1/321 (0.3%)	1	0/321 (0%)	0
Nervous system disorders
Seizure	1/321 (0.3%)	1	1/321 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
cough	0/321 (0%)	0	1/321 (0.3%)	1
Surgical and medical procedures
Abcessed tooth	0/321 (0%)	0	1/321 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/321 (0%)		0/321 (0%)

Limitations/Caveats

The study was an effectiveness trial so external vs. internal validity was emphasized. Many participants were lost to follow-up.

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.