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Trial registered on ANZCTR


Registration number
ACTRN12616000802404p
Ethics application status
Not yet submitted
Date submitted
9/06/2016
Date registered
20/06/2016
Date last updated
20/06/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of modified doses of varenicline on quitting smoking attempts in Townsville, Australia
Scientific title
A randomised, placebo-controlled, double-blinded clinical study assessing the effectiveness and safety of modified varenicline regimens in adult smokers motivated to quit
Secondary ID [1] 289235 0
None
Universal Trial Number (UTN)
Trial acronym
ITEV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoker 298805 0
Condition category
Condition code
Mental Health 298976 298976 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase 4, double-blinded, placebo-controlled clinical study with three intervention groups; Intervention Group 1 (IG1), Intervention Group 2 (IG2) and a Control Group (CG). The interventional medication is Varenicline tartrate oral tablets, using both the commercial 0.5mg and 1.0mg tablets. IG1 will be administered a step-up dose, IG2 will be administered a step-down dose, and the control group will take the standard varenicline regimen. Treatment will last for 16 weeks, with 12 weeks of non-treatment follow-up.

IG1: 0.5mg once daily for 7 days, 0.5mg twice daily for 7 days. 1.0mg once daily PLUS 0.5mg once daily for 7 days, 1.0mg twice daily for 11 weeks, two weeks of placebo.
IG2:Placebo for 2 weeks, 0.5mg once daily for 3 days, 0.5mg twice daily for 4 days, 1.0mg twice daily for 11 weeks, 0.5mg twice daily for 7 days, 0.5mg once daily for 7 days.
CG: Placebo for 2 weeks, 0.5mg once daily for 3 days, 0,5mg twice daily for 4 days, 1.0mg twice daily for 11 weeks, placebo for 2 weeks.

The tablets will be provided in Webster-paks(R) to improve ease of dosing, and to monitor tablets adherence during the study.
Intervention code [1] 294922 0
Treatment: Drugs
Comparator / control treatment
Control Group: Placebo for 2 weeks, 0.5mg once daily for 3 days, 0,5mg twice daily for 4 days, 1.0mg twice daily for 11 weeks, placebo for 2 weeks
Control group
Dose comparison

Outcomes
Primary outcome [1] 298502 0
The frequency, severity and duration of adverse events experienced, assessed through the use of self-reported daily questionnaires, and investigator-initiated questionnaires weekly throughout the entire study period. Questionnaires will prompt participants to note the date each adverse event is experienced, its severity on a scale from 1-10, and will encourage participants to include notes of importance relating to each adverse event.

Common adverse events likely to be reported include; nausea, vomiting, headache, constipation, insomnia, trouble sleeping, abnormal dreams, dizziness, and flatulence.
Timepoint [1] 298502 0
Entirety of participant enrollment from the baseline visit to the final visit at Week 28.
Primary outcome [2] 298503 0
The frequency, severity, and duration of withdrawal symptoms experienced, assessed through the use of the Minnesota Nicotine Withdrawal Scale (MNWS), a 4-point scale self-reported daily by participants, and investigator-initiated weekly throughout the entire study period.

Items included on the MNWS include: urge to smoke, depressed mood, irritability/frustration/anger, anxiety, difficulty concentrating, restlessness, increased appetite, difficulty falling asleep, and difficulty staying asleep.
Timepoint [2] 298503 0
Entirety of participant enrollment from the baseline visit to the final visit at Week 28
Primary outcome [3] 298673 0
The frequency, severity, and duration of cravings experienced, assessed through both the use of the first item in the MNWS, and the Questionnaire on Smoking Urges-Brief (QSU-Brief) (a 1-item questionnaire with a scale from 1-100).
Timepoint [3] 298673 0
Entirety of participant enrollment from the baseline visit to the final visit at Week 28
Secondary outcome [1] 324411 0
Adherence to medication during treatment, assessed through tablet counting of returned Webster-paks at each clinic visit during the treatment phase.
Timepoint [1] 324411 0
Assessed at weeks 4, 8, 12 and 16
Secondary outcome [2] 324939 0
Smoking abstinence rates (both 7-day point prevalence and 4-weeks continuous abstinence rates) are assessed through the use of self-reporting during telephone calls, and self-reporting with confirmation through carbon-monoxide breath tests during clinic visits.
Timepoint [2] 324939 0
Smoking status queried during each telephone call and clinic visit throughout entirety of study.

Eligibility
Key inclusion criteria
Smokers motivated to quit smoking.
Over 18 years old.
Able to attend multiple visits with a researcher in Townsville.
Smoke more than 10 Cigarettes per day.
Able to refrain from using any other smoking cessation medication, and any alternative form of tobacco during the study period.

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Is pregnant, breastfeeding, or planning to become pregnant during the study.
Has a recent history of unstable cardiovascular or psychiatric conditions (stability is considered as having had no medication changes or condition deterioration in the past 6 months).
Has a history of a suicide attempt, and or suicidal behaviour in the previous 2 years.
Has an alcohol or other substance abuse disorder.
Has a personal history of a psychosis (schizophrenia, post-traumatic stress disorder, or bipolar disorder).
Has recently used varenicline (in the past 6 months).
Is taking any of the following medications; Naltrexone, Insulin, Nortriptyline, Clonidine, theophylline, warfarin, anorexic agents, or steroids (inhaled, or short term oral corticosteroids are permitted).


Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be assigned a participant identifier number (PIN) which will be randomly allocated to one of the three treatment groups. PINs are assigned in random order, and will be sealed in individual envelopes with the assigned treatment group. Both the participants and investigator will be blinded, with breaking of the blind occurring only if participant safety is compromised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Generation of PINs and assignment to treatment groups will be performed using a simple computer generated randomisation of the PIN numbers, and a 'pick out of the hat' approach to assigning treatment groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Using GPOWER 3.1, it was determined that to detect a moderate effect size with 80% power, 119 completers are required, leading to a planned participant total of 201 to account for loss to follow up.
Data will be analysed using SPSS and the following:
- General Linear Models will be used to evaluate differences in the frequency, severity, and duration of adverse effects, cravings, and withdrawal symptoms.
- Logistic Regression and Survival Analysis to evaluate effect of treatment groups on smoking cessation and timing of cessation

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 5880 0
The Townsville Hospital - Douglas
Recruitment postcode(s) [1] 13325 0
4814 - Douglas
Recruitment postcode(s) [2] 13326 0
4810 - North Ward
Recruitment postcode(s) [3] 13327 0
4810 - Townsville

Funding & Sponsors
Funding source category [1] 293730 0
Commercial sector/Industry
Name [1] 293730 0
Pfizer Inc
Address [1] 293730 0
235 East 42nd Street. NY, NY 10017
Country [1] 293730 0
United States of America
Funding source category [2] 293731 0
Commercial sector/Industry
Name [2] 293731 0
Webster-Care
Address [2] 293731 0
17 - 19 Moore St, Leichhardt NSW 2040
Country [2] 293731 0
Australia
Funding source category [3] 293732 0
University
Name [3] 293732 0
James Cook University
Address [3] 293732 0
1 James Cook Drive, Townsville
QLD, 4814, Australia
Country [3] 293732 0
Australia
Primary sponsor type
Individual
Name
Aaron Drovandi
Address
Building 47 (Pharmacy), James Cook University
1 James Cook Drive, Townsville
QLD, 4814
Country
Australia
Secondary sponsor category [1] 292563 0
Hospital
Name [1] 292563 0
The Townsville Hospital
Address [1] 292563 0
100 Angus Smith Dr, Douglas QLD 4814
Country [1] 292563 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 295163 0
James Cook University Human Research Ethics Committee
Ethics committee address [1] 295163 0
Building 17, Room 128
1 James Cook Drive
Townsville, QLD, 4811
Ethics committee country [1] 295163 0
Australia
Date submitted for ethics approval [1] 295163 0
10/08/2016
Approval date [1] 295163 0
Ethics approval number [1] 295163 0
Ethics committee name [2] 295164 0
Townsville Hospital and Health Service Human Research Ethics Committee
Ethics committee address [2] 295164 0
Research Support Unit
IMB 52, PO Box 670
Townsville QLD 4810
Ethics committee country [2] 295164 0
Australia
Date submitted for ethics approval [2] 295164 0
30/07/2016
Approval date [2] 295164 0
Ethics approval number [2] 295164 0

Summary
Brief summary
Varenicline remains the most effective pharmacological agent in supporting smokers to quit, though its effectiveness in promoting long term abstinence is inhibited by a number of issues 1. A recent meta-analysis reported that varenicline caused an increase in discontinuation compared to placebo as a result of adverse events, negatively impacting medication adherence and the likelihood of a quit attempt being successful 2. As adherence to varenicline is a major predictor of success during a quit attempt, ensuring completion of the prescribed regimen is needed to optimise the likelihood of a successful quit attempt 3. An additional issue during varenicline treatment is the resurgence of cravings and withdrawal symptoms at the end of the prescribed treatment period. Experiencing these symptoms increase the likelihood of lapse and relapse after achieving initial abstinence 4.
The primary objective of this clinical study is to compare differences in safety and efficacy outcomes of three different varenicline regimens for smoking cessation over a treatment period of 16 weeks, followed by 12 weeks of follow-up. The regimens are designed to reduce the frequency and severity of adverse effects, cravings and withdrawal symptoms. The secondary objectives are a comparison of carbon monoxide (CO) confirmed continuous abstinence rates (CAR), 7-day point prevalence abstinence rates, and adherence to the study medication throughout treatment.
The primary endpoints are the frequency, severity and duration of adverse events, cravings and withdrawal symptoms. The secondary endpoints are 7 day point prevalence and CO confirmed continuous abstinence rates from weeks 12-16, and weeks 16-28, and medication adherence.
This study is a phase 4, randomized, double-blinded, placebo-controlled single-center study designed to evaluate the safety and efficacy of varenicline in motivated, smoking subjects allocated to a control group, step-up intervention group, or step-down intervention group. A total of up to 201 participants will be enrolled in to this study at a single site, with 67 participants randomly allocated in a 1:1:1 ratio to one of the three treatment groups. This will provide at least 80% power to detect a moderate effect in the primary endpoints.
Participants meeting eligibility criteria will enter the 16-week double-blind treatment phase, followed by a 12-week follow-up phase, with the study completing at week 28. Follow-up will continue for participants who cease treatment early. Participant enrollment will run from December 2016 to December 2017, with data analysis occurring during and after this period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65910 0
Mr Aaron Drovandi
Address 65910 0
Building 47 (Pharmacy), James Cook University
1 James Cook Drive, Townsville
QLD, 4814
Country 65910 0
Australia
Phone 65910 0
+61 7 4781 3437
Fax 65910 0
+61 7 4725 8108
Email 65910 0
aaron.drovandi@jcu.edu.au
Contact person for public queries
Name 65911 0
Mr Aaron Drovandi
Address 65911 0
Building 47 (Pharmacy), James Cook University
1 James Cook Drive, Townsville
QLD, 4814
Country 65911 0
Australia
Phone 65911 0
+61 7 4781 3437
Fax 65911 0
+61 7 4725 8108
Email 65911 0
aaron.drovandi@jcu.edu.au
Contact person for scientific queries
Name 65912 0
Mr Aaron Drovandi
Address 65912 0
Building 47 (Pharmacy), James Cook University
1 James Cook Drive, Townsville
QLD, 4814
Country 65912 0
Australia
Phone 65912 0
+61 7 4781 3437
Fax 65912 0
+61 7 4725 8108
Email 65912 0
aaron.drovandi@jcu.edu.au

No information has been provided regarding IPD availability
Summary results
No Results