Varenicline Versus Cytisine for Smoking Cessation in Primary Care Setting

• ClinicalTrials.gov Identifier: NCT04015414
• Recruitment Status: Completed
• First Posted: July 11, 2019
• Last Update Posted: November 3, 2022
• Sponsor: University of Zagreb
• Collaborators: University of Ljubljana School of Medicine, Slovenia; University of Zagreb School of Medicine; Harvard Medical School (HMS and HSDM)
• Information provided by (Responsible Party): Stjepan Oreskovic, University of Zagreb

Study Description

Brief Summary:

The overall goals of this study are to 1) assess awareness of interest in the use of pharmacotherapy for smoking cessation in Croatia and Slovenia, countries in Central Europe with very high smoking prevalence, and 2) investigate whether cytisine is at least as feasible and effective as varenicline in helping smokers to quit in a real-life setting: family medicine practices in Croatia and Slovenia. The investigators propose to survey patients from 40 primary care practices (20 in Croatia and 20 in Slovenia) to assess desire to quit smoking and awareness and interest in pharmacotherapy. Additionally, 380 patients with interest in quitting smoking will be randomly assigned to use varenicline or cytisine to help quit smoking.

The investigators hypothesize that cytisine is at least as feasible and effective as varenicline in helping smokers from primary care practices in Croatia and Slovenia to quit smoking.

Condition or disease	Intervention/treatment	Phase
Smoking Cessation	Drug: Varenicline; Drug: Cytisine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 352 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Varenicline Versus Cytisine for Smoking Cessation in the Primary Care Setting in Croatia and Slovenia - a Randomized Controlled Trial
• Actual Study Start Date: July 14, 2020
• Actual Primary Completion Date: September 15, 2022
• Actual Study Completion Date: November 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Varenicline (Champix); Varenicline treatment will start one week prior to the patient's target quit date at 0.5 mg/day for days 1-3, 0.5 mg twice daily for days 4-7. On the target quit date (day 8), the dose will be increased to 1 mg twice daily and maintained for day 8-week 12. Patients will receive weekly calls during the first 4 weeks and at weeks 8, 12, and 24 to inquire about medication adherence and smoking status, motivate the patient to take the medication, encourage them not to smoke, and ask about possible side effects or other issues.	Drug: Varenicline; 191 patients will receive varenicline for 12 weeks and regular phone calls with brief counseling Tabex: 188 patients will receive cytisine for 25 days and regular phone calls with brief counseling; Other Name: Champix
Active Comparator: Cytisine (Tabex); Patients will be asked to reduce their smoking during the first 4 days of treatment with aim to quit on the 5th day (target quit date). Cytisine treatment will follow standard manufacturer's dosing protocol of one tablet every 2 hours through the waking day (up to 6 tablets per day) for days 1-3, one tablet every 2.5 hours (up to 5 tablets per day) for days 4-12, one tablet every 3 hours (up to 4 tablets per day) for days 13-16, one tablet every 4-5 hours (3 tablets per day) for days 17-20, and one tablet every 6 hours (2 tablets per day) for days 21-25.	Drug: Cytisine; 185 patients will receive cytisine for 25 days and regular phone calls with brief counseling; Other Name: Tabex

Outcome Measures

Primary Outcome Measures :

1. Seven day abstinence from tobacco [ Time Frame: 12-weeks following target quit date ]
   Proportion of patients in the varenicline and cytisine groups who self-report seven-day abstinence from tobacco.

Secondary Outcome Measures :

1. Seven day abstinence from tobacco country and practice [ Time Frame: 4-weeks following target quit date ]
   Proportion of patients in the varenicline and cytisine groups who self-report seven-day abstinence from tobacco.
2. Seven day abstinence from tobacco [ Time Frame: 8-weeks following target quit date ]
   Proportion of patients in the varenicline and cytisine groups who self-report seven-day abstinence from tobacco.
3. Seven day abstinence from tobacco [ Time Frame: 24-weeks following target quit date ]
   Proportion of patients in the varenicline and cytisine groups who self-report seven-day abstinence from tobacco.
4. Seven day abstinence from tobacco [ Time Frame: 4, 8, 12, and 24 weeks following target quit date ]
   Repeated measures of proportion of patients in the varenicline and cytisine groups who self-report seven-day abstinence from tobacco
5. Continuous smoking cessation [ Time Frame: 4, 8, 12, and 24 weeks following target quit date ]
   Proportion of patients who self-report continuous smoking cessation in the varenicline and cytisine groups (5 cigarettes allowed)
6. Medication adherence [ Time Frame: 1, 2, 3, 4, 8, 12 weeks following target quit date ]
   Self report of adherence to assigned treatment protocol, including count of pills and stopping treatment (including reasons)
7. Side effects [ Time Frame: 4, 8, 12, and 24 weeks following target quit date ]
   Self-report of any unintended sign, symptom, or other health-related issue that occurs during treatment with varenicline or cytisine

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Receive care in one of forty family medicine practices in Croatia and Slovenia
• Aged 18 or older
• Current smokers
• Indicate a desire to stop smoking and to use pharmacotherapy.

Exclusion Criteria:

• Mental illness who cannot provide informed consent for the study
• Pregnant or breastfeeding.

Contacts and Locations

Locations

Croatia

University of Zagreb School of Medicine

Zagreb, Croatia, 10000

Slovenia

University of Ljubljana School of Medicine

Ljubljana, Slovenia, 1000

Sponsors and Collaborators

University of Zagreb

University of Ljubljana School of Medicine, Slovenia

University of Zagreb School of Medicine

Harvard Medical School (HMS and HSDM)

Investigators

• Principal Investigator: Stjepan Oreskovic, PhD; University of Zagreb School of Medicine
• Principal Investigator: Sanja Percac Lima, PhD, MD; Massachusetts General Hospital
• Study Chair: Hrvoje Tiljak, PhD; University of Zagreb School of Medicine
• Study Chair: Janez Rifel, PhD; University of Ljubljana School of Medicine
• Study Chair: Jeffrey M Ashbruner, PhD, MPH; Massachusetts General Hospital
• Study Chair: Zalika Klemenc Ketis, MD, PhD; University of Ljubljana School of Medicine
• Study Chair: Tin Oreskovic; IBM Chief Analytics Office, MIT-IBM AI Lab

More Information

• Responsible Party: Stjepan Oreskovic, Full Professor, University of Zagreb
• ClinicalTrials.gov Identifier: NCT04015414
• Other Study ID Numbers: GRAND / MEF Zagreb - LPPHR2018; WI231434 IIR ( Other Grant/Funding Number: Pfizer Inc., a Delaware corporation with an office of business at 235 East 42nd Street, New York, NY 10017 ("Pfizer" )
• First Posted: July 11, 2019
• Last Update Posted: November 3, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: After completion of the data collection and analysis

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs