Ignite Creation Date:
2024-05-05 @ 5:36 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00484692
Status:
COMPLETED
Last Update Posted:
2007-06-11
First Post:
2007-06-08
Brief Title:
Randomized Trial of Ultrashort Psychotherapy vs Sustained-Release Bupropion for Smoking Cessation
Sponsor:
Medical University Innsbruck
Organization:
Medical University Innsbruck
Study Overview
Official Title:
Randomized Clinical Trial Comparing a Medication ie Sustained-Release Bupropion Zyban With an Ultrashort 1 12 d Manual-Based Psychotherapeutic Intervention Psychodynamic Model Training
Status:
COMPLETED
Status Verified Date:
2007-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Smokers often reject drugs as smoking cessation aids Nonpharmacological interventions are notoriously under-evaluated
Methods
We conducted a randomized clinical trial in which we compared a medication ie sustained-release bupropion Zyban 413 subjects at the time of the trial the most efficacious pharmacological smoking cessation aid with an ultrashort psychotherapeutic intervention Psychodynamic Model Training 366 subjects a manual-based psychodynamically oriented 1 ½ day autosuggestion training Outcome criterion was 12-month self-reported continuous abstinence confirmed by urine cotinine levels below the level of detection 13 ngml or in an independent analysis by exhaled carbon monoxide of 10 ppm or less at all interviews conducted at 3 6 and 12 months
Smokers often reject drugs as smoking cessation aids Nonpharmacological interventions are notoriously under-evaluated
Methods
We conducted a randomized clinical trial in which we compared a medication ie sustained-release bupropion Zyban 413 subjects at the time of the trial the most efficacious pharmacological smoking cessation aid with an ultrashort psychotherapeutic intervention Psychodynamic Model Training 366 subjects a manual-based psychodynamically oriented 1 ½ day autosuggestion training Outcome criterion was 12-month self-reported continuous abstinence confirmed by urine cotinine levels below the level of detection 13 ngml or in an independent analysis by exhaled carbon monoxide of 10 ppm or less at all interviews conducted at 3 6 and 12 months
Detailed Description:
Study design
This randomized clinical trial was designed to compare the efficacy and safety of a manual-based 15-day psychotherapeutic intervention ie Psychodynamic Model Training with a medication ie sustained-release bupropion Zyban as smoking cessation aids In order to render the data comparable to previously obtained bupropion data the bupropion treatment regimen and study protocol closely followed that by Jorenby et al 19993 As an improvement over previous protocols3-5 nonsmoking status was verified not only by determination of exhaled carbon monoxide CO levels but also by tandem mass spectrometric LCMSMS analysis of urine cotinine67 a marker of higher sensitivity than CO8
Subjects screening inclusion and exclusion criteria and randomization
Female and male smokers were recruited between July 2005 and December 2005 by announcements in the local media press local radio stations and in the newsletter httpwwwstgkkatmediaDB104832PDF of the governmental Styrian Regional Health Care System Steiermaerkische Gebietskrankenkasse STGKK the sponsor of the present study Interested smokers were first screened by telephone interview and then scheduled for the study intake interview The first subject was enrolled in July 2005 and follow-up was completed in January 2007 Of a total of 951 persons screened 790 met the screening criteria and were enrolled and randomized to one of two treatments according to a randomization list in the care of the steering committee at the Medical University Innsbruck Great care was taken to preserve treatment allocation concealment Only after the subject had given hisher written consent a sealed envelope containing the treatment allocation was broken by the interviewer and presented to the subject The study protocol was registered with the European Medicines Agency emeaeuropaeu EudraCT-Nr 2005-006189-32 and was approved by the local governmental review board The study was conducted in compliance with the ethical principles of the Declaration of Helsinki wwwwmanetepolicyb3html accessibility verified May 16 2007 and the standards on good clinical practice developed by the International Conference on Harmonization wwwichorgcachecompo276-254-1html accessibility verified May 16 2007
Inclusion criteria were an age of at least 18 years a cigarette consumption of at least 15 cigarettes per day in the last 3 months and the willingness to contribute EUR 70 to the treatment costs regardless of the treatment modality Exclusion criteria as assessed by the study-site physicians were any psychiatric diagnosis except nicotine or caffeine dependence any current psychopharmacological treatment known hypersensitivity to bupropion epilepsy liver cirrhosis brain tumor pregnancy verified by an immunological test at the intake interview and 3 weeks after the first day of the first menses occurring within treatment lactation any serious or unstable cardiac renal hypertensive pulmonary endocrine or neurologic disorder ulcers dermatologic disorders current use of other smoking cessation treatments and regular use of any noncigarette tobacco product After induction of the first 620 subjects it became apparent that more subjects randomized to the bupropion group dropped out immediately after learning of their treatment allocation To compensate for this higher rejecter rate in the bupropion group the remaining 170 subjects were randomized to bupropion vs psychotherapy at a ratio of 21 Seven of the 420 subjects randomly allocated to the bupropion group and 4 of the 370 to the psychotherapy group were found to meet exclusion criteria by the studys physicians only after the randomization bupropion bulimia 3 cases of major depression 2 cases with antidepressant medication anticoagulant medication psychotherapy 4 cases with a previously undisclosed psychiatric diagnosis and had to be excluded before treatment started Therefore the final intention-to-treat ITT sample consisted of 413 subjects in the bupropion and 366 subjects in the psychotherapy group
Treatments
The treatment period in the sustained-release bupropion Zyban group was nine weeks3 following the protocol given in Zybans product information as provided by its manufacturer GlaxoSmithKline Vienna Austria After an initial medical consultation a dose run-up period of 1 week to a final 150 mg sustained-release bupropion twice daily on day 7 a target quitting date was set for the second week usually day 8 Subjects returned for a second visit scheduled between days 26 and 33 of the treatment to the studys physicians for a medical checkup and to receive the second 60-tablet package of Zyban Failure to show up for this second medical checkup was considered treatment failure
Psychodynamic Model Training is a manual9-based psychodynamically oriented ultrashort psychotherapeutic intervention consisting of a very brief psychoeducation and an initial training in autosuggestion techniques that are taught during a single 15-day program day 1 0900-2000 h day 2 0900 - 1300 h Subjects approximately 30 per group were introduced to five guided imagery scenarios aimed at strengthening the following psychotherapeutically defined aspects of functioning 1 self-worth self-determination self-assurance 2 self-acceptance 3 health vitality relaxation awareness of bodily functions 4 creativity self-worth remuneration and emotional reward for ones work and 5 ability to sustain intimate personal relationship
Follow-up period
Subjects of either group were contacted by telephone to schedule follow-up assessments in the study physicians offices at the Institute for Clinical Psychology Psychotherapy and Health Promontion Graz at the end of months 3 6 and 12 and had to present for the appointment within 36 h of the telephone call in order to facilitate the detection of any smoking During these assessments subjects were asked about their nonsmoking status their breathalyzer CO levels were determined by associates of the studys sponsor the STGKK and they had to provide a urine sample for cotinine analysis Family members of randomly selected subjects also received telephone calls from a staff member of the STGKK to confirm their nonsmoking status No relapse-prevention counseling was administered during the follow-up period
Assessments
At baseline demographic data medical and smoking history were obtained and vital signs and exhaled CO levels were determined The Beck Depression Inventory10 was used to assess depressive symptoms scores of 0 to 9 are considered to be normal scores of 10 to 18 indicated mild-to-moderate depression scores of 19 to 29 indicated moderate-to-severe derpession and scores of 30 to 63 indicate severe depression The Fagerström Tolerance Questionnaire1112 was used to quantify the severity of nicotine dependence scores of 0 to 11 with higher scores indicating more severe dependence A separate questionnaire contained the portion of the Structured Clinical Interview for the Diagnostic and Statistical Manual version 4 DSMIV13 concerning substance dependence disorders
During follow-up interviews CO levels were determined in the expired air by breathalyzer piCOsmokerlyzer wwwbedfontcom Urine samples were obtained and quantified for cotinine a major metabolite of nicotine with a urine elimination half-life around 20 h7 by HPLC coupled with tandem mass spectrometry LCMSMS as previously described14 The cotinine mass transition 177 80 mz standard curve internal standard 50 ngml d3-methadone was essentially linear up to the highest concentration tested ie 2000 ngml quadratic equation fit weighting 1x r099 The level of detection LOD was 13 ngml at a signalnoise ratio of 21 The level of quantification LOQ in the actual urine samples of the study was 30 ngml
Measures of outcome
The primary outcome criterion was a biochemicallypharmacologically-confirmed 12-month continuous abstinence as evidenced by self-reports of nonsmoking status in all interviews ie at 3 6 and 12 months Self-reports of nonsmoker status were confirmed by urine cotinine levels below the level of detection 13 ngmL at a signalnoise-ratio of 21 in the LCMSMS analysis at all 3 follow-up interviews Subjects in the bupropion group had to report abstinence from the target quitting date onwards subjects in the psychotherapy group had to report abstinence from the end of the 15-day program onwards Subjects who self-reported nonsmoker status but for which urine samples could not be collected or at any of the 3 follow-up time points or which refused to provide a urine sample at any of the 3 follow-up time points were considered smokers In order to better compare the data of the present study with previously published bupropion data34 nonsmoker status was confirmed independently of the urine cotinine analysis by exhaled carbon monoxide CO levels at or below 10 parts per million ppm at all 3 follow-up interviews following the nonsmoker criterion of Jorenby and coworkers for low-frequency follow-ups34 The secondary outcome was point prevalence of self-reported abstinence confirmed by urine cotinine levels below the level of detection for each follow-up time point Outcome criteria were assessed both in the ITT- and the completer-sample
Statistical analysis
The sample size of approximately 380 subjects per group was determined such that under standard conditions regarding power 80 and two-sided alpha level 005 the following differences between the two treatment groups may be detected continuous abstinence rates of 17 in one group vs 10 in the other or 23 vs 15 or 29 vs 20 Baseline comparisons of the two treatment groups were performed by the chi-square test for categorical data Students t-test for normally distributed and Mann-Whitney U-test for non-normally distributed numerical variables Differences between the two groups regarding primary 12-month continuous abstinence rate and secondary point prevalence of abstinence outcome criteria TEAE rates and rejecter rates were analysed by means of the chi-square test two-sided In order to quantify the differences between the two groups the Odds Ratio OR Relative Benefit RB in analogy to the Relative Risk and the Number Needed to Treat NNT were determined Agreement between the two detection methods cotinine level CO level was evaluated by the kappa coefficient significant differences in continuous abstinence rates between the two detection methods were determined by means of the McNemar test All analyses were performed by a certified statistician using the SPSS software wwwspsscom Measures of variance were either the standard deviation SD for the treatment groups baseline characteristics or the 95 confidence interval for OR RB and NNT
This randomized clinical trial was designed to compare the efficacy and safety of a manual-based 15-day psychotherapeutic intervention ie Psychodynamic Model Training with a medication ie sustained-release bupropion Zyban as smoking cessation aids In order to render the data comparable to previously obtained bupropion data the bupropion treatment regimen and study protocol closely followed that by Jorenby et al 19993 As an improvement over previous protocols3-5 nonsmoking status was verified not only by determination of exhaled carbon monoxide CO levels but also by tandem mass spectrometric LCMSMS analysis of urine cotinine67 a marker of higher sensitivity than CO8
Subjects screening inclusion and exclusion criteria and randomization
Female and male smokers were recruited between July 2005 and December 2005 by announcements in the local media press local radio stations and in the newsletter httpwwwstgkkatmediaDB104832PDF of the governmental Styrian Regional Health Care System Steiermaerkische Gebietskrankenkasse STGKK the sponsor of the present study Interested smokers were first screened by telephone interview and then scheduled for the study intake interview The first subject was enrolled in July 2005 and follow-up was completed in January 2007 Of a total of 951 persons screened 790 met the screening criteria and were enrolled and randomized to one of two treatments according to a randomization list in the care of the steering committee at the Medical University Innsbruck Great care was taken to preserve treatment allocation concealment Only after the subject had given hisher written consent a sealed envelope containing the treatment allocation was broken by the interviewer and presented to the subject The study protocol was registered with the European Medicines Agency emeaeuropaeu EudraCT-Nr 2005-006189-32 and was approved by the local governmental review board The study was conducted in compliance with the ethical principles of the Declaration of Helsinki wwwwmanetepolicyb3html accessibility verified May 16 2007 and the standards on good clinical practice developed by the International Conference on Harmonization wwwichorgcachecompo276-254-1html accessibility verified May 16 2007
Inclusion criteria were an age of at least 18 years a cigarette consumption of at least 15 cigarettes per day in the last 3 months and the willingness to contribute EUR 70 to the treatment costs regardless of the treatment modality Exclusion criteria as assessed by the study-site physicians were any psychiatric diagnosis except nicotine or caffeine dependence any current psychopharmacological treatment known hypersensitivity to bupropion epilepsy liver cirrhosis brain tumor pregnancy verified by an immunological test at the intake interview and 3 weeks after the first day of the first menses occurring within treatment lactation any serious or unstable cardiac renal hypertensive pulmonary endocrine or neurologic disorder ulcers dermatologic disorders current use of other smoking cessation treatments and regular use of any noncigarette tobacco product After induction of the first 620 subjects it became apparent that more subjects randomized to the bupropion group dropped out immediately after learning of their treatment allocation To compensate for this higher rejecter rate in the bupropion group the remaining 170 subjects were randomized to bupropion vs psychotherapy at a ratio of 21 Seven of the 420 subjects randomly allocated to the bupropion group and 4 of the 370 to the psychotherapy group were found to meet exclusion criteria by the studys physicians only after the randomization bupropion bulimia 3 cases of major depression 2 cases with antidepressant medication anticoagulant medication psychotherapy 4 cases with a previously undisclosed psychiatric diagnosis and had to be excluded before treatment started Therefore the final intention-to-treat ITT sample consisted of 413 subjects in the bupropion and 366 subjects in the psychotherapy group
Treatments
The treatment period in the sustained-release bupropion Zyban group was nine weeks3 following the protocol given in Zybans product information as provided by its manufacturer GlaxoSmithKline Vienna Austria After an initial medical consultation a dose run-up period of 1 week to a final 150 mg sustained-release bupropion twice daily on day 7 a target quitting date was set for the second week usually day 8 Subjects returned for a second visit scheduled between days 26 and 33 of the treatment to the studys physicians for a medical checkup and to receive the second 60-tablet package of Zyban Failure to show up for this second medical checkup was considered treatment failure
Psychodynamic Model Training is a manual9-based psychodynamically oriented ultrashort psychotherapeutic intervention consisting of a very brief psychoeducation and an initial training in autosuggestion techniques that are taught during a single 15-day program day 1 0900-2000 h day 2 0900 - 1300 h Subjects approximately 30 per group were introduced to five guided imagery scenarios aimed at strengthening the following psychotherapeutically defined aspects of functioning 1 self-worth self-determination self-assurance 2 self-acceptance 3 health vitality relaxation awareness of bodily functions 4 creativity self-worth remuneration and emotional reward for ones work and 5 ability to sustain intimate personal relationship
Follow-up period
Subjects of either group were contacted by telephone to schedule follow-up assessments in the study physicians offices at the Institute for Clinical Psychology Psychotherapy and Health Promontion Graz at the end of months 3 6 and 12 and had to present for the appointment within 36 h of the telephone call in order to facilitate the detection of any smoking During these assessments subjects were asked about their nonsmoking status their breathalyzer CO levels were determined by associates of the studys sponsor the STGKK and they had to provide a urine sample for cotinine analysis Family members of randomly selected subjects also received telephone calls from a staff member of the STGKK to confirm their nonsmoking status No relapse-prevention counseling was administered during the follow-up period
Assessments
At baseline demographic data medical and smoking history were obtained and vital signs and exhaled CO levels were determined The Beck Depression Inventory10 was used to assess depressive symptoms scores of 0 to 9 are considered to be normal scores of 10 to 18 indicated mild-to-moderate depression scores of 19 to 29 indicated moderate-to-severe derpession and scores of 30 to 63 indicate severe depression The Fagerström Tolerance Questionnaire1112 was used to quantify the severity of nicotine dependence scores of 0 to 11 with higher scores indicating more severe dependence A separate questionnaire contained the portion of the Structured Clinical Interview for the Diagnostic and Statistical Manual version 4 DSMIV13 concerning substance dependence disorders
During follow-up interviews CO levels were determined in the expired air by breathalyzer piCOsmokerlyzer wwwbedfontcom Urine samples were obtained and quantified for cotinine a major metabolite of nicotine with a urine elimination half-life around 20 h7 by HPLC coupled with tandem mass spectrometry LCMSMS as previously described14 The cotinine mass transition 177 80 mz standard curve internal standard 50 ngml d3-methadone was essentially linear up to the highest concentration tested ie 2000 ngml quadratic equation fit weighting 1x r099 The level of detection LOD was 13 ngml at a signalnoise ratio of 21 The level of quantification LOQ in the actual urine samples of the study was 30 ngml
Measures of outcome
The primary outcome criterion was a biochemicallypharmacologically-confirmed 12-month continuous abstinence as evidenced by self-reports of nonsmoking status in all interviews ie at 3 6 and 12 months Self-reports of nonsmoker status were confirmed by urine cotinine levels below the level of detection 13 ngmL at a signalnoise-ratio of 21 in the LCMSMS analysis at all 3 follow-up interviews Subjects in the bupropion group had to report abstinence from the target quitting date onwards subjects in the psychotherapy group had to report abstinence from the end of the 15-day program onwards Subjects who self-reported nonsmoker status but for which urine samples could not be collected or at any of the 3 follow-up time points or which refused to provide a urine sample at any of the 3 follow-up time points were considered smokers In order to better compare the data of the present study with previously published bupropion data34 nonsmoker status was confirmed independently of the urine cotinine analysis by exhaled carbon monoxide CO levels at or below 10 parts per million ppm at all 3 follow-up interviews following the nonsmoker criterion of Jorenby and coworkers for low-frequency follow-ups34 The secondary outcome was point prevalence of self-reported abstinence confirmed by urine cotinine levels below the level of detection for each follow-up time point Outcome criteria were assessed both in the ITT- and the completer-sample
Statistical analysis
The sample size of approximately 380 subjects per group was determined such that under standard conditions regarding power 80 and two-sided alpha level 005 the following differences between the two treatment groups may be detected continuous abstinence rates of 17 in one group vs 10 in the other or 23 vs 15 or 29 vs 20 Baseline comparisons of the two treatment groups were performed by the chi-square test for categorical data Students t-test for normally distributed and Mann-Whitney U-test for non-normally distributed numerical variables Differences between the two groups regarding primary 12-month continuous abstinence rate and secondary point prevalence of abstinence outcome criteria TEAE rates and rejecter rates were analysed by means of the chi-square test two-sided In order to quantify the differences between the two groups the Odds Ratio OR Relative Benefit RB in analogy to the Relative Risk and the Number Needed to Treat NNT were determined Agreement between the two detection methods cotinine level CO level was evaluated by the kappa coefficient significant differences in continuous abstinence rates between the two detection methods were determined by means of the McNemar test All analyses were performed by a certified statistician using the SPSS software wwwspsscom Measures of variance were either the standard deviation SD for the treatment groups baseline characteristics or the 95 confidence interval for OR RB and NNT
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FWF grant P16394-B05 | None | None | None |