Varenicline for Smoking Cessation in Hospitalized Patients With Psychiatric Disorders

NCT03809897 | Withdrawn Phase 4

• 1 other identifier: BRU-VCN-2017
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

Varenicline increases smoking abstinence rates compared to bupropion, nicotine patch or placebo in outpatients with psychiatric disorders. The American Psychiatric Association identifies psychiatric hospitalizations as an ideal opportunity to treat tobacco dependence. However, no previous studies have tested whether varenicline may improve smoking cessation rates compared to nicotine patch in hospitalized patients with mental illness. Additionally, varenicline has shown to be safe for mental health stable outpatients, but safety in psychiatric inpatients is unknown. Multisite open trial controlled study designed to assess varenicline's effectiveness on smoking cessation compared to nicotine patch, in patients who are discharged from a psychiatric unit. Treatment will start during hospitalization and last 12 weeks followed by a non-treatment follow-up phase for 4 weeks. Safety will be assessed by comparing the incidence of adverse events. Participants will be randomized to receive varenicline or nicotine patch during 12 weeks. All participants will receive smoking cessation counseling.

Conditions

Tobacco Use Cessation; Psychiatric Disorders

Outcome Measures

Primary Outcomes (24)

• Assessment of effectiveness: smoking abstinence rates

  To compare smoking abstinence rates of varenicline relative to nicotine patch measured by CO-confirmed continuous abstinence rate.

  Between week 9 and week 16

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Randomization day

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 1

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 2

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 3

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 4

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 5

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 6

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 7

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 8

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 9

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 10

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 11

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 12

• Assessment of safety: incidence of emergent "severe" neuropsychiatric event

  Differences in the incidence of emergent "severe" neuropsychiatric event. Solicited neuropsychiatric adverse events (AEs) will be collected by the use of Neuropsychiatric Adverse Event Interview (NAEI).

  Week 13

• Psychiatric Evaluation done by a psychiatrist

  Psychiatric Evaluation done by a psychiatrist as a measure of Mental health assessment. Although psychiatric assessment will not use a specific tool, an interview with the patient will be delivered in order to assess psychopathology not covered by the instruments of the protocol, deepen in possible adverse events that may arise with the NAEI (Neuropsychiatric Adverse Event Interview) and readjust psychiatric medication if needed.

  From the screening day, on the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.

• Clinical Global Impression of Severity (baseline)

  The CGI-S is a clinician rated instrument measuring the severity of a subject's psychiatric condition on a 7 point scale at time of assessment, relative to clinician's past experience in patients with same diagnosis.

  It is assessed in the randomization day (day 1)

• Clinical Global Impression of Improvement

  The CGI-I is a clinician rated instrument that measures change in subject's psychiatric condition on a 7 point scale ranging from 1 (very much improved) to 7 (very much worse).

  During hospitalization, from week 1 to week 4, and on the post-discharge weeks 5, 7, 9, 12 and 16.

• The Hospital Anxiety and Depression Scale (HADS)

  The Hospital Anxiety and Depression Scale (HADS) is a subject self-report scale and contains 14 items rated on 4-point Lickert-type scales. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression, being 0 not having anxiety or depression and 21 very anxious or depressed. The HADS uses a scale and therefore the data returned from the HADS is ordinal.

  From the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.

• Columbia Suicide-Severity Rating Scale (C-SSRS)

  The Columbia Suicide-Severity Rating Scale (C-SSRS) rates an individual's degree of suicidal ideation which may be indicative of an individual's intent to complete suicide. It contains six "yes" or "no" questions in which respondents are asked to indicate whether they have experienced several thoughts or feelings relating to suicide over the past month and behaviors over their lifetime and past 3 months. Each question addresses a different component of the respondent's suicide ideation severity and behavior. 1. wish to be dead 2. non-specific suicidal thoughts 3-5: more specific suicidal thoughts and intent to act 6: suicidal behavior over the respondent's lifetime and past 3 months An answer of "yes" to any of the six questions may indicate a need for referral to a trained mental health professional and an answer of "yes" to questions 4, 5 or 6 indicate high-risk.

  From the screening day, on the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.

• Measurement of Nicotine Use Inventory (NUI)

  The Measurement of Nicotine Use Inventory (NUI) is a questionnaire regarding use of cigarettes and other nicotine -containing products during the treatment period or tobacco products during the non-treatment period. The NUI consists of the following two questions: whether the person has smoked any cigarettes (even a puff) since the last contact and whether he has smoked any other tobacco products (eg, pipe, cigars, snuff, chew) since the last contact.

  From the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12, 14 and 16.

• Minessota Nicotine Withdrawal Scale (MNWS)

  The Minessota Nicotine Withdrawal Scale (MNWS) is a subject self-report scale and contains 8 items (e.g., irritability, anxious, depressed mood, difficulty concentrating, increased appetite, insomnia, restless...) on a 5-point Lickert-type scales measuring nicotine withdrawal symptoms. Subjects were given a score on each item on a scale of 0 (not present) to 4 (severe). Summed (total) score excluding craving represent subject's symptoms of tobacco withdrawal, ranging from 0 to 32. We calculated a craving for tobacco score and a total score of withdrawal symptoms excluding craving. The higher score represent more sever craving and withdrawal.

  From the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.

• Fagerström test for Cigarette Dependence (FTCD)

  Cigarrette dependence was assessed using the Fagerström Test of Nicotine Dependence (FTND), which consists of six questions. Question 1 of the FTND read as follows: "How soon after you wake up do you smoke your first cigarette?" A total score was calculated as a sum of the six questions, with lower scores indicating lower dependence on nicotine: 0-2, very low dependence; 3-4, low dependence; 5, medium dependence; 6-7, high dependence; and 8-10, very high dependence.

  It is assessed in the randomization day (day 1)

• End-expiratory exhaled carbon monoxid (exhaled CO)

  Breath carbon monoxide is the level of carbon monoxide in a person's exhalation. It can be measured in a breath carbon monoxide test, generally by using a carbon monoxide breath monitor (breath CO monitor), such as for motivation and education for smoking cessation and also as a clinical aid in assessing carbon monoxide poisoning.

  From the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.

Study Arms (2)

Varenicline

EXPERIMENTAL

Patients randomized to the experimental arm will receive 3 days of 0.5 mg of varenicline, followed by 4 days of 1 mg of varenicline (until day 7). Finally, until week 12, they will receive 2 mg of varenicline. Varenicline is supplied in capsules and taken orally.

Drug: Varenicline

Nicotine patch

ACTIVE COMPARATOR

Patients randomized to nicotine patch will receive 8 weeks of 21 mg patch followed by 2 weeks of 14 mg patch and 2 weeks of 7 mg patch.

Drug: Nicotine patch

Interventions

Varenicline DRUG

All participants randomized to varenicline will be titrated to the full dose during the first week and continued up to week 12 following standard dosage. This would be independent of time of discharge, so patients will continue the same treatment after discharge up to complete the 12 weeks.

Also known as: Champix

Varenicline

Nicotine patch DRUG

Patients randomized to nicotine patch will receive 8 weeks of 21mg patch followed by 2 weeks of 14 mg patch and 2 weeks of 7 mg patch.

Also known as: Nicotinell

Nicotine patch

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years old, inclusive.
• Good understanding of protocol to informed consent.
• Hospitalized for a mental health condition at one of the three acute psychiatric facilities who participate in this study.
• Having at least a psychiatric disorder according to DSM-5.
• Living in Barcelona city or in the metropolitan area.
• Not being at high risk of self-injury or suicidal behavior, in the opinion of the Investigator.
• Smoking an average of at least 10 cigarettes per day during the year before hospital admission.
• Females who are not childbearing potential (surgical sterilized or at least 2 years postmenopausal) and who are not nursing may be included. Females who are childbearing potential may be included if they agree to avoid pregnancy during the study, and agree to use a birth control method.
• Able to comply with schedule visits, treatment plan and study procedures.
• Signed and dated informed consent indicating that the participant has been informed of all aspects of the study. In case of involuntary admission, a judge will consent the participant is capable to participate.

You may not qualify if:

• History of suicide attempt in the previous year.
• Not agree to abstain from cannabis.
• Taking bupropion.
• Recent (less than two months) myocardial infarction.
• Previous adverse reaction that the investigator considers due to varenicline/nicotine patch and of sufficient concern that further exposure to varenicline/nicotine patch would be inadvisable.
• Severe renal insufficiency.
• Pregnancy or lactation.
• Other severe acute or chronic medical or psychiatric condition that would make the subject inappropriate for entry into this study.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead
• Clínica Galatea: collaborator
• Hospital Sant Rafael: collaborator
• Hospital de Sant Pau: collaborator

Study Sites (4)

Galatea Clinic

Barcelona, 08017, Spain

Location

Sant Rafael Hospital

Barcelona, 08035, Spain

Location

Vall d'Hebron Institute of Research

Barcelona, 08035, Spain

Location

Hospital de Sant Pau

Barcelona, 08041, Spain

Location

Related Publications (8)

• Colton CW, Manderscheid RW. Congruencies in increased mortality rates, years of potential life lost, and causes of death among public mental health clients in eight states. Prev Chronic Dis. 2006 Apr;3(2):A42. Epub 2006 Mar 15.

  PMID: 16539783 BACKGROUND

• Callaghan RC, Veldhuizen S, Jeysingh T, Orlan C, Graham C, Kakouris G, Remington G, Gatley J. Patterns of tobacco-related mortality among individuals diagnosed with schizophrenia, bipolar disorder, or depression. J Psychiatr Res. 2014 Jan;48(1):102-10. doi: 10.1016/j.jpsychires.2013.09.014. Epub 2013 Sep 27.

  PMID: 24139811 BACKGROUND

• Prochaska JJ. Ten critical reasons for treating tobacco dependence in inpatient psychiatry. J Am Psychiatr Nurses Assoc. 2009 Dec;15(6):404-9. doi: 10.1177/1078390309355318. No abstract available.

  PMID: 20336177 BACKGROUND

• Prochaska JJ, Fletcher L, Hall SE, Hall SM. Return to smoking following a smoke-free psychiatric hospitalization. Am J Addict. 2006 Jan-Feb;15(1):15-22. doi: 10.1080/10550490500419011.

  PMID: 16449089 BACKGROUND

• Prochaska JJ, Hall SE, Delucchi K, Hall SM. Efficacy of initiating tobacco dependence treatment in inpatient psychiatry: a randomized controlled trial. Am J Public Health. 2014 Aug;104(8):1557-65. doi: 10.2105/AJPH.2013.301403. Epub 2013 Aug 15.

  PMID: 23948001 BACKGROUND

• Hickman NJ, Prochaska JJ, Dunn LB. Screening for understanding of research in the inpatient psychiatry setting. J Empir Res Hum Res Ethics. 2011 Sep;6(3):65-72. doi: 10.1525/jer.2011.6.3.65.

  PMID: 21931239 BACKGROUND

• 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.

  PMID: 11086367 BACKGROUND

• Stockings EA, Bowman JA, Baker AL, Terry M, Clancy R, Wye PM, Knight J, Moore LH, Adams MF, Colyvas K, Wiggers JH. Impact of a postdischarge smoking cessation intervention for smokers admitted to an inpatient psychiatric facility: a randomized controlled trial. Nicotine Tob Res. 2014 Nov;16(11):1417-28. doi: 10.1093/ntr/ntu097. Epub 2014 Jun 17.

  PMID: 24939916 BACKGROUND

Related Links

• Efficacy of a universal smoking cessation intervention initiated in inpatient psychiatry and continued post-discharge: A randomised controlled trial.
• Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial.

MeSH Terms

Conditions

Tobacco Use Cessation; Mental Disorders

Interventions

Varenicline; Tobacco Use Cessation Devices; Nicotine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Therapeutics; Solanaceous Alkaloids; Alkaloids; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Eugeni Bruguera, MD

  Vall d'Hebron Institute of Research, Galatea Clinic

  PRINCIPAL INVESTIGATOR

• Dolores Braquehais, PhD

  Galatea Clinic

  PRINCIPAL INVESTIGATOR

• Naia Sáez-Francàs, PhD

  Sant Rafael Hospital

  PRINCIPAL INVESTIGATOR

• Cristina Pinet, MD

  Hospital de Sant Pau

  PRINCIPAL INVESTIGATOR

• Gemma Nieva, PhD

  Vall d'Hebron Institute of Research, Galatea Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive varenicline or nicotine patch during 12 weeks.

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: January 18, 2019
• Study Start: January 1, 2019
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: March 12, 2019

Record last verified: 2019-01

Locations

ES (4)