Varenicline In-Patient Study (VIP)
|First Received Date ICMJE||August 3, 2011|
|Last Updated Date||October 31, 2014|
|Start Date ICMJE||August 2011|
|Primary Completion Date||October 2014 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Quit rate (those who have quit smoking and have not smoked in the 7 days prior to the assessment date) for those in the varenicline group versus the placebo group [ Time Frame: 4 weeks after beginning study ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01413516 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Varenicline In-Patient Study|
|Official Title ICMJE||A Two-Part Pilot Study of Dosing, Safety and Efficacy of Varenicline Initiated During an Acute Smoke-free Hospitalization and Continued Post-Hospitalization|
This Investigator Initiated Research Award (IIR Award #WS981308) is a two-part pilot study that aims to examine acceptability and feasibility of varenicline use during an acute (72-hr) smoke-free hospitalization (Part 1) and 4-weeks post-hospitalization (Part 2). The sample, 40 women and 40 men, will be hospitalized patients smoking at least 10 cigarettes/day prior to hospitalization. Intention to quit smoking will not be required for study participation. Using a double-blinded, placebo-controlled, randomized design, participants will receive varenicline (0.5 mg BID as tolerated) or placebo during their hospitalization (Part 1) and will continue their study medication (placebo or active drug) for 4 weeks post-hospitalization (Part 2). Abstinence status will be examined at 4 weeks post-hospitalization.
At the study end, the investigators will provide a letter to the study participant for his/her outpatient primary care provider that details their current smoking status and provides information on cessation medication options, including varenicline. It will be up to the primary care provider to manage the patients' treatment of tobacco dependence following study close. Of note, two-thirds of health insurance plans now cover the cost of varenicline so the cost to participants is likely to be minimal. Since participants will be recruited from Stanford Hospital, the investigators anticipate nearly all will have an appointment to see their primary care physician 4 to 5 weeks post-hospital discharge. Additionally, the investigators will refer participants to the state's toll-free quitline, whereby patients on Medi-Cal can obtain free cessation medication.
The sample, 6 women and 11 men, are hospitalized patients recruited from the medical units at Stanford Hospital and Clinics who report smoking at least 10 cigarettes per day prior to hospitalization, have confirmed tobacco use by cotinine testing (saliva sample), and an expected hospitalization of at least a day duration from the date of study enrollment. Intention to quit smoking is not required for study participation.
Fortunately, varenicline does not have any significant known drug-by- drug interactions. Varenicline does not impact cytochrome P450. Varenicline is primarily cleared via the kidneys. Study exclusion criteria are: dementia; Alzheimer's Disease; delirium; drug and/or alcohol dependence; suicidal ideation; end-stage renal disease (i.e., on dialysis); hypertensive crisis; stroke; MI with severe cardiac damage; pregnancy or breastfeeding; non-English speaking; complete homelessness; or currently engaged in tobacco treatment.
Study staff check patients' medical records as well as consult with clinical staff prior to approach for study enrollment to determine eligibility and discuss any safety concerns the clinical team may have. In consulting with cardiologist and study physician, Dr. Neal Benowitz, we have concluded that we are excluding only patients who are currently hospitalized for MI and who have had severe cardiac damage as a result of the MI. Per Dr. Benowitz, those with stable cardiovascular disease diagnoses can still safely enroll in the study. Furthermore, the FDA has indicated in the same release that varenicline has been found effective in helping patients with cardiovascular disease quit smoking. In cases of severe renal impairment (estimated creatinine clearance <30 mL/min), medical staff will consult with participants' physician to assess the appropriateness for study enrollment. Furthermore patients with a history of stroke, brain aneurysms and masses, or other cognitive disorders including seizure disorders, Parkinson's, Huntington's disease, meningitis, or brain masses and/or a neurological disorder or cognitive condition (except for dementia; Alzheimer's Disease) may still be enrolled in the study. However patients who have been admitted because of an acute exacerbation of symptoms or problems related to those disorders or who are being admitted for diagnostic workups for, or beginning treatment of those disorders are excluded.
Part 1 is conducted at Stanford Hospital and Clinics. This proposal, which is to provide motivational/behavioral counseling with all smokers, including those not yet ready to quit, surpasses current standard care practice.
Patients identified as current smokers on the nursing intake form, completed with all new admissions, are recruited for the study. Using a double blinded, placebo controlled, randomized design, participants receive varenicline (0.5 mg BID as tolerated) or placebo during their hospitalization. As detailed in the study consent form, dose escalation will proceed as 0.5 mg BID as tolerated and increased to 1 mg twice daily to get the participants up to a therapeutic dose efficiently in a smoke-free clinical setting. If patients are discharged within 24 hours then we follow the standard dosing protocol rather than testing the accelerated dosing. Side effects are assessed daily by study staff who consult with clinical pharmacists on the unit to determine if the dose should be titrated more slowly or if the side effects can be clinically managed. In the Onken 2006 JAMA study that compared 0.5 mg BID nontitrated and titrated and 1.0 mg BID nontitrated and titrated in an outpatient setting, the main difference by dose and titration groups was in the incidence of nausea but the difference was significant only in the 1 mg BID conditions. The incidence of nausea between the 0.5 mg twice-daily nontitrated group (22.6%) and 0.5 mg twice-daily titrated varenicline group (16.3%) were not significantly different from placebo (14.9%). Further, the discontinuation rate due to nausea was low (< 5% of subjects in each treatment group). Measured vital signs and results of clinical laboratory tests and ECGs demonstrated no clinically meaningful differences between varenicline and placebo in the Onken study. Titration of varenicline is based on tolerance, not pharmacology. The half-life is 24 hours. At Stanford, the study drug is dispensed by the hospital research pharmacy overseen by Marty Hamilton, PharmD who administers the placebo/active medication as appropriate.
To support medication compliance and abstinence post hospitalization, participants receive a stage tailored cessation manual and 30 min clinician delivered medication and stage tailored cessation counseling.
Part I examines: (1) feasibility of the accelerated dosing schedule, (2) frequency and severity of adverse effects, and (3) efficacy in managing nicotine withdrawal symptoms. Primary repeated measures include established assessments of thoughts on smoking and smoking-related behavior, nicotine withdrawal, craving and urge, and sleep quality; heart rate; and adverse effects assessed by structured checklist with ratings of mild, moderate, or severe graded per FDA Common Toxicity Criteria.
Additionally, we measure and evaluate two important biomarkers. First, we examine simultaneous measurement of plasma, saliva and urine varenicline levels during hospitalization to validate saliva and urine as noninvasive methods of monitoring compliance with varenicline for future studies. Plasma, saliva, and urine are collected for use in this study only and is not to be used or tested for future studies. Secondly, smokers tend to regulate their nicotine intake, which has led investigators to study the rate of nicotine metabolism as a potential predictor of response to smoking cessation treatment. The ratio of the nicotine metabolites trans 3' hydroxycotinine (3 HC) to cotinine, which can be measured in smokers' blood, saliva or urine, is highly correlated with nicotine clearance, and has been shown to be a useful biomarker for predicting smoking cessation in response to pharmacotherapy (6). The proposed trial would be the first to test the 3 HC to cotinine ratio as a moderator of treatment outcome in a study of varenicline and in a sample that includes unmotivated to quit smokers and those with co occurring medical and psychiatric and/or substance abuse disorders.
Given that some inpatients manage to make it outside to smoke regardless of the medical center policy we collect expired breath samples by CO monitor daily during hospitalization.
Part 2 examines (1) participant compliance with a 4 week course of medication (placebo or active drug) continuing post hospitalization; (2) nicotine withdrawal symptoms post hospitalization; and (3) lapse, relapse and abstinence rates. Follow up assessments are held at 1 week (by phone) and 4 weeks (in person) post hospital discharge. The 1 week call assesses any tobacco use since leaving the hospital and documents time to first cigarette and ratings of cigarette enjoyment among those who report smoking. The 4 week follow up repeats the measures from Part I. A urine varenicline level is collected to determine medication compliance and is compared to a traditional pill count. Additionally, we assess lapses, relapses, and smoking status by self report, confirmed with CO and urinary cotinine. Figure 1 summarizes the study design. If a participant self- reports a return to smoking post-hospitalization during the 1 or 4 week follow-up, and a sample from a blood draw completed within 24 hours of admission for smokers who smoke less than 20 cigarettes per day or within 48 hours of admission for smokers who smoke 20 or more cigarettes per day has not been collected, we also ask the participant to schedule a time within the study period to come in and complete this draw with our nurse practitioner or with CTSI.
Figure 1. Study Protocol
Part 1: Hospitalization
Study Day 1:
• Repeat measures of nicotine withdrawal, craving, sleep quality, heart rate, adverse events and obtain CO.
Study Day 3 (for participants who are still hospitalized:
Part 2: Post hospitalization
1 week Post Hospitalization: Phone Contact
During the eligibility screening process, in addition to a screener form with items based on our inclusion and exclusion criteria, we also use the DAST Questionnaire, the AUDIT Alcohol Questionnaire, and Beck Depression Inventory (BDI) item 9. These three questionnaires help us to rule out patients with illegal substances or alcohol dependence and those with suicidal ideation respectively.
Primary repeated measures include: established assessments of stage of change, nicotine withdrawal (WSC), craving and urge (QSU-Brief and CES), and sleep quality; heart rate; adverse effects assessed by structured checklist with ratings of mild, moderate, or severe graded per FDA Common Toxicity Criteria; and current medications.
Descriptive measures include the Taste and Sensation Survey; assessments of physical and mental health functioning (SF-12, CESD); the Fagerstrom Test of Nicotine Dependence (FTND); a smoking history questionnaire that we use in all of our smoking studies that assesses age first started smoking, years of smoking, and prior quit attempts.
We also ask participants to complete two questionnaires (at baseline and at the 1 month follow-up) asking about exposure to onscreen smoking to assess both aspects of exposure to smoking in movies on relapse among the people in this study.
At enrollment each subject gets a different list of 49 movies selected at random from the top grossing films of the last 5 years, plus "Handsome JacK', a title for a movie that does not exist, as a control. This will determine which films participants had seen from the 500 top-grossing movies (PG, PG-13, and R rated) released between 2007 and 2011.
Following the Beach method, the number of smoking (or other tobacco) occurrences in each film (obtained from the www.scenesmoking.orgdatabase) is added up to get a measure of total exposure of historical to onscreen smoking for each participant .
At 1 month followup, each subject would be given a similar list of all films but it will be 20 titles selected from movies that were among the top 10 in theaters or on video in the month since the baseline visit. This list is generated weekly using data from www.scenesmoking and the total number of occurrences seen in recent films will be computed.
A contact form collects information for tracking participants with home and cell phone numbers, mail and e-mail addresses, usage of Facebook, and information on up to two physician contacts and three alternative sources of contacts, and also asks for the best 4 ways to contact the participant. Study staff also e-mail study participants from our Facebook account using the e-mail account they provided.
Part 2 and follow-up assessments will take place at the research staff offices at the Stanford Prevention Research Center, or with the consent of the participant, at participant's outpatient medical offices, residences, and community sites.
Data collection is carefully monitored including the administration time required to assess participant burden. Each measure is summarized and tabulated as appropriate with attention paid to unusual or out of range values. The two conditions are compared on the key measures using the appropriate statistical test. While the purpose of the study is not to conduct a definitive comparison of the conditions, such quantitative analyses provide useful information for the next phase of research.
Plasma, urine, and saliva samples collected throughout this study is only used for this study and is not banked for future studies.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Condition ICMJE||Smoking Cessation|
|Study Arm (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||October 2014|
|Primary Completion Date||October 2014 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
- Study exclusion criteria are: dementia or other brain injury precluding ability to participate; Alzheimer's Disease; Parkinson's Disease; Huntington's Disease; meningitis; seizure disorder of a sustained nature; delirium; brain surgery; drug and/or alcohol dependence; suicidal ideation; end-stage renal disease (i.e., on dialysis); hypertensive crisis; stroke; myocardial infarction (MI) with severe cardiac damage; pregnancy or breastfeeding; non-English speaking; complete homelessness; or currently engaged in tobacco treatment. Study staff will consult with clinical staff prior to approach for study enrollment. In cases of severe renal impairment (estimated creatinine clearance <30 mL/min), medical staff will consult with participants' physician to assess the appropriateness for study enrollment.
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01413516|
|Other Study ID Numbers ICMJE||VIP|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Judith Prochaska, Stanford University|
|Study Sponsor ICMJE||Stanford University|
|Information Provided By||Stanford University|
|Verification Date||October 2014|
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