Clinical trial NCT01623505: Reducing Cardiovascular Disease by Combining Smoking Cessation Pharmacotherapy and Behavioural Counseling
Official title: Interventions for Cardiovascular Disease: "Real-World" Effectiveness of Combined Pharmacotherapy and Behavioural Counseling for Smoking Cessation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Smoking Cessation
Psychiatric Illness
Keywords: Smoking Cessation
Psychiatric Illness
Pharmacotherapy
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Ontario
First posted: 2012-06-20
Enrollment: 738
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Research Aims

The aims of this research study are:

1. To determine which of the following three smoking cessation medications is most effective in achieving cessation:

   * Nicotine Patch
   * Nicotine Patch + gum or inhaler
   * Varenicline (Champix;
2. To investigate how often participants experience neuropsychiatric symptoms over the course of their cessation attempt and to assess whether:

   * They occur more often when taking one medication versus another
   * They occur more often in those with or without psychiatric illnesses.

Hypotheses to be Tested

The hypotheses to be tested include the following:

1. The CO-confirmed continuous abstinence rate from 5 weeks to 52 weeks following a target quit date will be significantly higher in smokers receiving long-term transdermal NRT in combination with other NRT products or those receiving varenicline compared to those receiving transdermal NRT alone.
2. Some participants will experience neuropsychiatric symptoms during their cessation attempt, and those in the varenicline group will experience a greater incidence of neuropsychiatric symptoms than those in the groups receiving transdermal NRT alone or in combination with other NRT products. Patients with psychiatric illnesses will report higher levels of withdrawal symptoms than those without psychiatric illnesses.

Detailed description: Participants will be recruited from the UOHI Smoking Cessation Clinic and via media advertisements. Following the baseline assessment, participants will be randomly assigned to one of three groups:

1. 10-week standard regimen of transdermal NRT (NRT);
2. Long duration of transdermal NRT in combination with other NRT products (NRT+); or
3. Varenicline (VR).

Participants assigned to the "NRT" standard regimen group will follow a 10-week treatment of nicotine patches alone.

Participants assigned to the "NRT+" long-duration group will follow the same regimen as the NRT group, but will not be limited to a fixed declining dose strategy, nor limited to a 10-week duration (potential maximum dosage of 35mg/day and maximum treatment duration of up to 22 weeks). Participants will also be provided with other NRT products (i.e., gum or inhaler).

Participants assigned to the "VR" group will start the medication on the day of the baseline assessment and set a target quit date any time within the 8 to 14 day period after baseline. Participants will receive a 12-week supply of varenicline with a possible extension of up to 24 weeks.

All participants will receive six 15-minute counselling sessions from a nurse-counsellor specializing in smoking cessation in accordance with nursing best-practice guidelines. These sessions occur at 1, 3, 5, 8, and 10 weeks post target quit date. Counselling sessions will focus on practical counselling (problem solving and skills training) and social support.

During the treatment phase, participants will complete questionnaires measuring withdrawal and neuropsychiatric symptoms at 1, 3, 5, 8, and 10 weeks. These questionnaires will also be completed at 22 and 52 weeks after the target quit date.

Eligibility criteria: Inclusion Criteria:

* Participant is a current smoker (≥ 10 cigarettes per day in the preceding\\ six months);
* Participant is willing to make a quit attempt in the 2-4 weeks after initial screening for eligibility;
* Participant is 18 years of age and older;
* Participant is willing to provide informed consent.

Exclusion Criteria:

* Participant is currently using or has used any intervention medications in the previous 6 months (i.e, Champix (varenicline); and/or Nicotine replacement therapy (patch, gum, inhaler, lozenge));
* Participant has contraindication(s) to any of the following smoking cessation medications:

  * Nicotine replacement therapy (allergic reaction to adhesive; serious cardiac arrhythmias (e.g., tachycardia); participant is during the immediate post-myocardial infarction period (i.e. incident has occurred within the last 10 days); severe or worsening angina pectoris; participant has had a recent cerebral vascular accident);
  * Varenicline (end-stage renal disease; use of cimetidine (by participants with severe renal impairment); previous allergic reaction to varenicline);
* Pregnant or breastfeeding women or those intending to become pregnant in the next year;
* Current or previous (in the last 3 months) substance abuse;
* Unable to provide informed consent due to unstable psychiatric symptoms (e.g., active, untreated psychosis or suicidality);
* Participant is unable to read and understand English or French;
* In order to prevent contamination across groups, only one person per household may participate.

Primary outcomes:
measure: The primary outcome will be measured at 5, 10, 22, and 52 weeks after the target quit date and include: CO confirmed continuous abstinence from 5-10 weeks, 5-22 weeks and 5-52 weeks.
timeFrame: 5-10 weeks, 5-22 weeks, and 5-52 weeks post target quit date
Secondary outcomes:
measure: The secondary outcome will include withdrawal and neuropsychiatric symptoms (e.g., depression, anxiety, suicidal ideation, anger/aggression). These variables will be measured at 1, 3, 5, 8, 10, 22, and 52 weeks following the target quit date.
timeFrame: 1, 3, 5, 8, 10, 22, and 52 weeks post target quit date
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Insitute - Prevention and Wellness Centre
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Heather E Tulloch, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Andrew Pipe, MD
role: STUDY_CHAIR
affiliation: Ottawa Heart Institute Research Corporation
name: Robert Reid, MBA PhD
role: STUDY_CHAIR
affiliation: University of Alberta
name: Charl Els, MD
role: STUDY_CHAIR
References:
citation: Aubin HJ, Bobak A, Britton JR, Oncken C, Billing CB Jr, Gong J, Williams KE, Reeves KR. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Thorax. 2008 Aug;63(8):717-24. doi: 10.1136/thx.2007.090647. Epub 2008 Feb 8.
citation: Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):47-55. doi: 10.1001/jama.296.1.47.
citation: Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction. 2004 Jan;99(1):29-38. doi: 10.1111/j.1360-0443.2004.00540.x.
citation: Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med. 2008 Aug;35(2):158-76. doi: 10.1016/j.amepre.2008.04.009.
citation: Stapleton JA, Watson L, Spirling LI, Smith R, Milbrandt A, Ratcliffe M, Sutherland G. Varenicline in the routine treatment of tobacco dependence: a pre-post comparison with nicotine replacement therapy and an evaluation in those with mental illness. Addiction. 2008 Jan;103(1):146-54. doi: 10.1111/j.1360-0443.2007.02083.x. Epub 2007 Nov 19.
citation: Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA. 2000 Nov 22-29;284(20):2606-10. doi: 10.1001/jama.284.20.2606.
citation: Warner KE, Burns DM. Hardening and the hard-core smoker: concepts, evidence, and implications. Nicotine Tob Res. 2003 Feb;5(1):37-48. doi: 10.1080/1462220021000060428.
citation: Grant BF, Hasin DS, Chou SP, Stinson FS, Dawson DA. Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry. 2004 Nov;61(11):1107-15. doi: 10.1001/archpsyc.61.11.1107.
citation: Slovinec D'Angelo ME, Reid RD, Hotz S, Irvine J, Segal RJ, Blanchard CM, Pipe A. Is stress management training a useful addition to physician advice and nicotine replacement therapy during smoking cessation in women? Results of a randomized trial. Am J Health Promot. 2005 Nov-Dec;20(2):127-34. doi: 10.4278/0890-1171-20.2.127.
citation: Tulloch HE, Pipe AL, Els C, Clyde MJ, Reid RD. Flexible, dual-form nicotine replacement therapy or varenicline in comparison with nicotine patch for smoking cessation: a randomized controlled trial. BMC Med. 2016 Jun 7;14:80. doi: 10.1186/s12916-016-0626-2.
citation: Tulloch HE, Pipe AL, Clyde MJ, Reid RD, Els C. The Quit Experience and Concerns of Smokers With Psychiatric Illness. Am J Prev Med. 2016 Jun;50(6):709-718. doi: 10.1016/j.amepre.2015.11.006. Epub 2015 Dec 17.