Smoking Cessation Versus Long-term Nicotine Replacement Among High-risk Smokers

Long-term NRT has not been studied in patients with COPD, and smokers in the United States with COPD are still asked to choose between immediate quitting or continued smoking. The purpose of this study is to see if guided maintenance therapy (GMT), using long-term NRT, might prove to be a reasonable alternative to the standard approach of asking patients to quit immediately. The investigators believe that GMT with long-term NRT will reduce overall exposure to cigarette smoke, reduce harm related to smoking, and ultimately lead to greater quit rates.

In this study, 398 smokers with COPD will be randomly assigned to either receive: 1) traditional smoking cessation (SC) or 2) long-term, guided maintenance therapy with NRT (GMT). The SC intervention will be based on a standard approach to smoking cessation, including smoking cessation counseling supplemented with combination NRT (a nicotine patch plus the patient's choice of gum or lozenge) if they are willing to make a quit attempt. The GMT intervention will consist of counseling, focused on medication adherence and smoking reduction, plus 52 weeks of combination NRT. After 3, 6 and 12 months of treatment, we will compare the two treatments based on their effects on smoking cessation, number of cigarettes smoked, exposure to carbon monoxide and smoking-related carcinogens, COPD symptoms, breathing function, and smoking-related hospitalizations or death. The investigators will also analyze the data in such a way that will be able to identify which patients are most likely to benefit from treatment. This analysis will allow patients to estimate their chances of success based on their own personal characteristics and which treatment they choose.

The investigators study addresses research priorities identified in recent smoking cessation guidelines and builds upon the input of our Patient Advisory Panel and our Stakeholder Advisory Committee. This study reflects the interests expressed by smokers in prior surveys and addresses the limited reach and effectiveness of traditional approaches to smoking cessation. If our GMT approach is effective, our study could change the recommendations provided in clinical practice guidelines and change the way that insurance companies pay for smoking cessation treatment. GMT could provide an alternative for millions of smokers with COPD who are not currently benefiting from traditional approaches to smoking cessation

Study Overview

• Status: Completed
• Conditions: Smoking; Pulmonary Disease, Chronic Obstructive; Tobacco Use Disorder
• Intervention / Treatment: Drug: Nicotine replacement therapy; Other: Standard Smoking Cessation; Other: Extended Nicotine Replacement Therapy

Detailed Description

BACKGROUND Smokers with chronic obstructive pulmonary disease (COPD) recognize the dangers of continued smoking and would like to quit, but for most of them the idea of going 'cold turkey' is too intimidating. Many of these smokers would like to cut back on the amount that they smoke as part of a longer term path to quitting. Long-term nicotine replacement therapy (NRT) might allow them to do this. Long-term NRT is safe; it can reduce the rewarding effects of cigarettes, reduce the amount that people smoke, and increase quit rates. Long-term NRT has not, however, been studied in patients with COPD, and smokers in the United States with COPD are still asked to choose between immediate quitting or continued smoking. The purpose of this study is to evaluate the relative benefits of a third option: guided maintenance therapy with long-term NRT. We believe that long-term NRT could reduce overall exposure to cigarette smoke, reduce harm related to smoking, and ultimately lead to greater quit rates.

OBJECTIVES

1. Compare the benefits of traditional smoking cessation (SC) versus guided maintenance therapy (GMT) with NRT for smokers with COPD.
2. Estimate rates of smoking cessation and other patient-desired outcomes based on patient-specific characteristics and treatment choice (SC or GMT).

METHODS In this study, we will randomize 398 smokers with COPD to one of two treatment arms: 1) traditional smoking cessation (SC) or 2) long-term, guided maintenance therapy with NRT (GMT). Participants in the SC arm will receive a standard approach to smoking cessation, including smoking cessation counseling supplemented with combination NRT (nicotine patch plus choice of gum or lozenge) if they are willing to make a quit attempt. Participants in the GMT arm will receive counseling focused on medication adherence and smoking reduction plus 52 weeks of combined NRT. Outcomes will be measured at 3, 6 and 12 months post-randomization and will assess rates of smoking cessation, number of cigarettes smoked, exposure to carbon monoxide and smoking-related carcinogens, and clinical outcomes including respiratory symptoms, respiratory function, and smoking-related hospitalizations or death. In addition to directly comparing outcomes in the two treatment arms, our novel classification and regression tree analysis will allow us to identify subgroups of patients most likely to benefit from treatment and will allow patients to estimate their projected outcomes given their personal history and their choice of therapy.

PATIENT OUTCOMES (PROJECTED) This study will show how long-term NRT compares to a traditional smoking cessation program in helping smokers quit, reduce cigarette exposure, lower exposure to carcinogens, and reduce risk for death and hospitalizations. If our hypothesis is correct, this program could dramatically alter treatment choices for the millions of smokers in the United States with COPD that have been frustrated in their attempts to quit.

• Study Type: Interventional
• Enrollment (Actual): 398
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or older
• Physician-diagnosed COPD
• Smoke 5 or more cigarettes/day
• Smoke cigarettes on 25 or more of the last 30 days
• Speak either English or Spanish
• Willing to take nicotine replacement therapy for up to 1 year and participate in study procedures

Exclusion Criteria:

• Reside in a facility that does not allow smoking
• Don't have an address and telephone
• Unstable cardiac condition (e.g. unstable angina or myocardial infarction in the past 30 days)
• Pregnant or breastfeeding
• Terminal illness with less than 12 month life expectancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Smoking Cessation; Participants in the standard smoking cessation (SC) arm will receive a standard approach to smoking cessation, including smoking cessation counseling supplemented with 10 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) if they are willing to make a quit attempt.	Drug: Nicotine replacement therapy; Other Names: nicotine patch, nicotine gum, nicotine lozenge; Other: Standard Smoking Cessation; Participants in the standard smoking cessation (SC) arm will receive a standard approach to smoking cessation, including smoking cessation counseling supplemented with 10 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) if they are willing to make a quit attempt.
Experimental: Extended Nicotine Replacement Therapy; Participants in the guided maintenance therapy (GMT) arm will receive counseling focused on medication adherence and smoking reduction plus up to 52 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) regardless of their interest in quitting.	Drug: Nicotine replacement therapy; Other Names: nicotine patch, nicotine gum, nicotine lozenge; Other: Extended Nicotine Replacement Therapy; Participants in the guided maintenance therapy (GMT) arm will receive counseling focused on medication adherence and smoking reduction plus up to 52 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) regardless of their interest in quitting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smoking Abstinence (Point Prevalent)	7-day point prevalent abstinence at 12 months, confirmed by exhaled CO <=10	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Abstinence	6 month sustained abstinence as measured by self-report at 6 and 12 months and confirmed by CO at 6 and 12 months. Participants who were confirmed as non-smokers by carbon monoxide (CO) at both Month 6 and Month 12 were considered to have "6-month sustained abstinence."	Month 6 through Month 12
Quit Attempts	Number of self-reported quit attempts over one year. At Month 3 and Month 6, participants reported the number of quit attempts in the last 3 months. At Month 12, participants reported the number of quit attempts in the last 6 months.	Month 3, Month 6, Month 12
Average Cigarettes Per Day	Average number of cigarettes per day over one year. Participants were asked at Month 3, Month 6, and Month 12 "During the past 7 days, on those days that you smoked, what was the average number of cigarettes or little cigars smoked per day?"	Month 3, Month 6, Month 12
Carbon Monoxide Exposure	Carbon monoxide (CO) exposure over 12 months. At Month 3, Month 6, and Month 12, participants completed an expired carbon monoxide laboratory test, which measured CO in parts per million.	Month 3, Month 6, Month 12
Carcinogen Exposure	Creatinine-adjusted NNAL (4-(methylnitrosamino)-1-(3)pyridyl-1-butanol)) exposure over 12 months. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and NNAL.	Month 3, Month 6, Month 12
Respiratory Function	Change in respiratory function, as measured by spirometry (FEV1), at 12 months post-randomization.	Month 12
Respiratory Symptoms	Respiratory symptoms as measured by the COPD Assessment Test (CAT) respiratory questionnaire. Participants completed this 8-item assessment at Month 3, Month 6, and Month 12. Scores range from 0 to 40, with higher levels indicating higher impact of COPD on well-being and daily life.	Month 3, Month 6, Month 12
Respiratory-related Hospital Visits	Number of respiratory-related hospital admissions and emergency room visits. Participants were asked how many times they had visited the ED or were admitted to the hospital for respiratory-related problems at Month 3, Month 6, and Month 12	Month 3, Month 6, Month 12
Cardiac-related Hospital Visits	Number of cardiac-related hospital admissions and emergency room visits. Participants were asked how many times they had visited the ED or were admitted to the hospital for cardiac-related problems at Month 3, Month 6, and Month 12.	Month 3, Month 6, Month 12
7-day Abstinence	Self-reported and biochemically verified 7-day abstinence. Participants were asked at Month 3, Month 6, and Month 12, "Have you smoked any cigarettes or little cigars, even a puff, in the past 7 days?" They also completed an exhaled carbon monoxide lab test at Month 3, 6 and 12. Biochemical verification= exhaled CO <=10 ppm. Month 12 biochemically verified abstinence is the primary outcome, and is not reported in this table.	Month 3, Month 6, Month 12
Cotinine	Cotinine over 12 months, adjusted for creatinine. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and cotinine.	Month 3, Month 6, Month 12
Average Cigarettes Per Day (Continued Smokers Only)	Average number of cigarettes per day over one year, among continued smokers. All participants were asked "During the past 7 days, on those days that you smoked, what was the average number of cigarettes smoked per day?" at Month 3, Month 6, and Month 12. This analysis looks at the number of cigarettes per day among participants who were still smoking.	Month 3, Month 6, Month 12
Carbon Monoxide Exposure (Continued Smokers Only)	Carbon monoxide (CO) exposure over 12 months. At Month 3, Month 6, and Month 12, participants completed an expired carbon monoxide laboratory test, which measured CO in parts per million. This analysis looks at CO among those continuing to smoke.	Month 3, Month 6, Month 12
Carcinogen Exposure (Continued Smokers Only)	Creatinine-adjusted NNAL (4-(methylnitrosamino)-1-(3)pyridyl-1-butanol)) exposure over 12 months. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and NNAL. This analysis looks at NNAL among continuing smokers only.	Month 3, Month 6, Month 12
Cotinine (Continued Smokers Only)	Cotinine over 12 months, adjusted for creatinine. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and cotinine. This analysis looks at NNAL among continuing smokers only.	Month 3, Month 6, Month 12

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Edward F Ellerbeck, MD, University of Kansas

Publications and helpful links

General Publications

• Ellerbeck EF, Nollen N, Hutcheson TD, Phadnis M, Fitzgerald SA, Vacek J, Sharpe MR, Salzman GA, Richter KP. Effect of Long-term Nicotine Replacement Therapy vs Standard Smoking Cessation for Smokers With Chronic Lung Disease: A Randomized Clinical Trial. JAMA Netw Open. 2018 Sep 7;1(5):e181843. doi: 10.1001/jamanetworkopen.2018.1843.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: May 23, 2014
• First Submitted That Met QC Criteria: May 27, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): October 6, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: smoking cessation; nicotine; tobacco use cessation products
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: STUDY00000666; CER-1306-02901 (Other Identifier: PCORI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will create a clean, de-identified copy of our dataset. It will be available to other researchers, upon request. We will make data available to users under a data sharing agreement that provides for (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed. Data will be saved as SAS or SPSS files, saved to disk, encrypted, and mailed to users. A copy of our analytic code used to generate our primary outcomes paper(s) will also be available on request. Given that this study does not meet the threshold for data sharing requirements, the costs of data preparation and shipping will be borne by the requester.