Clinical trial NCT03809897: Varenicline for Smoking Cessation in Hospitalized Patients With Psychiatric Disorders
Official title: An Effectiveness and Safety Study of Varenicline for Smoking Cessation in Hospitalized Patients With Psychiatric Disorders
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Tobacco Use Cessation
Psychiatric Disorders
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
Collaborators: name: Clínica Galatea
name: Hospital Sant Rafael
name: Hospital de Sant Pau
First posted: 2019-01-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to receive varenicline or nicotine patch during 12 weeks.
Primary purpose: TREATMENT

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.

Detailed description: Varenicline has shown to increase abstinence rates compared to other pharmacological interventions (including nicotine patch) or placebo in outpatients with psychiatric disorders. Safety of varenicline in this population has also been stated as adverse events are similar to other smoking cessation medications.

Taking into account that varenicline has shown to increase abstinence rates in outpatients with psychiatric disorders compared to other smoking cessation medications, and no previous studies have measured the impact of initiating varenicline during psychiatric hospitalization, this study will compare varenicline to nicotine patch initiated during hospitalization on smoking abstinence rates (treatment will last 12 weeks; and there will be additional 4 weeks of non-treatment).

Regarding safety, inpatient wards are probably the best setting to test safety as any adverse effect can be reported immediately and in case of an intervention needed, this can be provided at once.

This study will have three phases: screening phase (1), treatment phase (2a and 2b), and non-treatment phase (3).

1. Screening phase: Psychiatrists and psychologists will be responsible for informing to potential participants about the study, and check eligibility for each patient. Investigators will give informed consent and information sheet to the participant, and all doubts will be resolved appropriately. If subject decides to participate the informed consent will be signed. The screening period will take place during first 72 hours after admission and participants will be randomized before 96 hours after admission.
2. Treatment phase: Treatment will take 12 weeks, therefore varenicline and nicotine patch will be dispensed during hospitalization and after discharge up to complete 12 weeks. 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. 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.

   1. During hospitalization: All participants will be assessed regarding their psychiatric and drug use history (including smoking) as well as past and current psychiatric disorders diagnosed by their psychiatrist. Adverse events (volunteered, observed, or solicited) will be also evaluated and recorded by their psychiatrist. Serious adverse events will be considered as an untoward medical occurrence at any dose that results in death, or is life-threatening, or requires prolongation of the hospitalization, or results in persistent or significant disability/incapacity, or results in congenital anomaly birth defect (following the same criteria of other studies). In case of serious adverse events (SAEs) at any point of the study, Principal Investigators will report to Pfizer within 24 hours of first awareness of the event. Cigarette Dependence, Tobacco withdrawal, Global Clinical Impression, nicotine use, suicide ideation/behavior, anxiety and depression will be assessed via scales and questionnaires by a trained smoking cessation psychologist. This psychologist will be also in charge of delivering weekly a motivationally tailored smoking cessation group counseling (30-45 minutes) following an adaptation of the manualized curriculum. A nurse will be responsible for measuring the end-expiratory exhaled CO, record body height and weight, vital signs (blood pressure and heart rate) and dispense medication.
   2. After discharge: There will be weekly visits until week 5, and visits at weeks 7, 9 and 12. Post-hospitalization visits will include tobacco use assessment, mental health assessment, adverse-events assessment, smoking cessation counseling and varenicline or nicotine patch delivery up to following visit. A psychiatrist will be responsible for assessing adverse-events and mental health. A psychologist will be responsible for delivering smoking cessation counseling tailored to each participant's needs according to the manualized curriculum and assessing tobacco use, withdrawal, suicide ideation/behavior, Global Clinical Impression, anxiety and depression. Counseling and mental health assessment will be conducted by the same professional whenever possible. A nurse will be responsible for measuring the end-expiratory exhaled CO, record body weight, vital signs (blood pressure and heart rate) and dispense medication. Whenever participant does not attend a study visit, counseling and Nicotine Use Inventory (NUI) will be delivered by telephone.
3. Non-treatment phase: This will include a telephone visit at week 14 and a face-to-face visit at week 16. Telephone visit will be made by the psychologist and it will include tobacco use assessment and smoking cessation counseling. A psychiatrist will be responsible for assessing adverse-events and mental health at week 16 visit and a psychologist will assess tobacco use, withdrawal, suicide ideation/behavior, Global Clinical Impression, anxiety and depression, and deliver smoking cessation counseling. Counseling and mental health assessment will be conducted by the same professional whenever possible. Also at this point,an End-of-study questionnaire will be completed. A nurse will be responsible for measuring the end-expiratory exhaled CO, record body weight and vital signs (blood pressure and heart rate). Whenever participant does not attend a study visit, NUI will be delivered by telephone. In case of early termination at any point of the study, an End-of-study questionnaire will be also completed.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 65 years old, inclusive.
2. Good understanding of protocol to informed consent.
3. Hospitalized for a mental health condition at one of the three acute psychiatric facilities who participate in this study.
4. Having at least a psychiatric disorder according to DSM-5.
5. Living in Barcelona city or in the metropolitan area.
6. Not being at high risk of self-injury or suicidal behavior, in the opinion of the Investigator.
7. Smoking an average of at least 10 cigarettes per day during the year before hospital admission.
8. 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.
9. Able to comply with schedule visits, treatment plan and study procedures.
10. 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.

Exclusion Criteria:

1. History of suicide attempt in the previous year.
2. Not agree to abstain from cannabis.
3. Taking bupropion.
4. Recent (less than two months) myocardial infarction.
5. 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.
6. Severe renal insufficiency.
7. Pregnancy or lactation.
8. Other severe acute or chronic medical or psychiatric condition that would make the subject inappropriate for entry into this study.

Primary outcomes:
measure: Assessment of effectiveness: smoking abstinence rates
timeFrame: Between week 9 and week 16
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Randomization day
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 1
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 2
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 3
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 4
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 5
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 6
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 7
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 8
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 9
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 10
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 11
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 12
measure: Assessment of safety: incidence of emergent "severe" neuropsychiatric event
timeFrame: Week 13
measure: Psychiatric Evaluation done by a psychiatrist
timeFrame: 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.
measure: Clinical Global Impression of Severity (baseline)
timeFrame: It is assessed in the randomization day (day 1)
measure: Clinical Global Impression of Improvement
timeFrame: During hospitalization, from week 1 to week 4, and on the post-discharge weeks 5, 7, 9, 12 and 16.
measure: The Hospital Anxiety and Depression Scale (HADS)
timeFrame: From the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.
measure: Columbia Suicide-Severity Rating Scale (C-SSRS)
timeFrame: 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.
measure: Measurement of Nicotine Use Inventory (NUI)
timeFrame: 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.
measure: Minessota Nicotine Withdrawal Scale (MNWS)
timeFrame: From the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.
measure: Fagerström test for Cigarette Dependence (FTCD)
timeFrame: It is assessed in the randomization day (day 1)
measure: End-expiratory exhaled carbon monoxid (exhaled CO)
timeFrame: From the randomization day, weekly during hospitalization (week 1 to week 4) and on the post-discharge weeks 5, 7, 9, 12 and 16.
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Galatea Clinic
city: Barcelona
country: Spain
facility: Sant Rafael Hospital
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Research
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
Study officials:
affiliation: Vall d'Hebron Institute of Research, Galatea Clinic
name: Eugeni Bruguera, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Galatea Clinic
name: Dolores Braquehais, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sant Rafael Hospital
name: Naia Sáez-Francàs, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Sant Pau
name: Cristina Pinet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vall d'Hebron Institute of Research, Galatea Clinic
name: Gemma Nieva, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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: 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.