Clinical Trial to Evaluate the Efficacy of Smoking Cessation

Smoking Cessation Clinical Trial

— COMBIVAR  

Official title:

Randomized Double-blind Trial of Two Parallel Groups Design to Evaluate the Efficacy of Smoking Cessation With Combined (Varenicline Plus Nicotine Patches) Versus Monotherapy (Varenicline Plus Placebo Patches)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01538394
• Other study ID #: VAR/01/011
• Status: Completed
• Phase: Phase 4
• First received: February 14, 2012
• Last updated: October 17, 2013
• Start date: January 2012
• Est. completion date: June 2013

Study information

• Verified date: October 2013
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy of smoking cessation by using varenicline as monotherapy (VRN + placebo patches) or combined therapy (VRN + nicotine patches).

Description:

Seven first-line pharmacotherapies are currently available and recommended by clinical practice guidelines for treating tobacco dependence, all of them have been proven to be effective for increasing tobacco abstinence rates when used as monotherapy. However, not all smokers are able to quit with monotherapy. Some smokers may benefit from combination therapy that includes the simultaneous use of different nicotine replacement therapies (NRTs) or medications with different mechanisms of action (e.g. NRT and bupropion). Combination therapy with different drugs may provide a therapeutic advantage by increasing serum nicotine concentrations, and may capitalize on synergy obtained from two different mechanisms of action. This is why controversy exists regarding this approach as the cost effectiveness of this approach has not been clearly demonstrated neither if the genetic profile determine different treatment responses.

Data from a varenicline pharmacokinetic study have documented that among smokers not instructed to quit and who continued smoking during treatment , varenicline was associated with a 60-80 % of reduction of number of cigarettes and, on the other hand, with a diminution of plasmatic nicotine and cotinine concentrations. (See some studies and trials in the Background Information).

This , led to hypotheses that : a) varenicline not saturate completely all acetylcholinergic receptors with a incomplete response and ; b) varenicline replace incompletely the dopaminergic effect of smoking, with continuous craving. The investigators considered that some smokers may need NRT in addition to varenicline to reduce withdrawal and cravings to smoke.

Finally, available data suggests that combination therapy may increase abstinence rates compared with monotherapy [OR: 2.4 (2.1- 2.7)] without a significant increase of adverse events. So the periodicity, regimen/dose, and periods of combined treatment may be considered as safe as the monotherapy even in an off-label indication.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 322
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Aged 18 to 65 years old

• Smoking 20 or more cigarettes per day

• Wants to stop smoking(seeking treatment)

• No period of smoking abstinence longer than 3 months in the past year

• Be able to give informed consent to participate

• Complete the study questionnaires

• Female smokers will be eligible providing they are not breastfeeding, pregnant (negative pregnancy test) or at risk of becoming pregnant

Exclusion Criteria:

• Previous use of nicotine transdermal patches or varenicline (VRN) in the last 6 months

• Cigar, pipe and oral tobacco users who do not smoke 20 or more cigarettes per day

• Those who meet the criteria contra-indicating nicotine patches or VRN use, as described in the Summaries Product Characteristics

• Those with previous severe adverse reactions to nicotine patch or to VRN

• Those currently taking either medication for smoking cessation that they are unwilling to stop or taking medication with a known influence on smoking cessation that they should not stop (e.g. nortriptyline for depression)

• Those who are non-Spanish neither Catalan speakers

• Those deemed unsuitable for the study by their smoking cessation physicians; -- Unstable diseases within the previous 6 months

• Diagnoses of or treatment for major depression last 6 months or psychotic disorder; or drug or alcohol dependence within the previous 12 months

• Skin disorders that cause a difficulty of nicotine absorption by patches as Psoriases as well as general dermatitis

• Clinically significant renal or hepatic impairment or dysfunction

• Pregnant or breast-feeding women

• women who do not use neither want to use any effective anticonceptive method.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver)

Related Conditions & MeSH terms

• Smoking Cessation

Intervention

Drug:
• Varenicline

• Nicotine patches

• Placebo (nicotine patches)

Locations

Country	Name	City	State
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitari de Bellvitge	L'hospitalet de Llobregat	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Josep Maria Ramon Torrell, PhD

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the efficacy of combined therapy (VRN+nicotine patches) versus monotherapy (VRN+placebo patches) in smoking cessation assessed as continuous abstinence rate (CAR) from week 2 to week 12.	The primary endpoint will be the continuous abstinence rate (CAR) from week 2 (w2) to week 12 (w12) measured objectively during the treatment phase by the CO exhaled.	Participants will be followed for the duration of treatment, 12 weeks.	No
Secondary	i) Determine safety of combined therapy (VRN+nicotine patches) versus monotherapy (VRN+placebo patches)	The secondary endpoints will be related to efficacy [continued abstinence rate (CAR) from week 2 to week 52, (CAR) from week 2 to week 6, (CAR) from week 2 to week 24, (CAR) from week 2 to week 36; point abstinence rate (PAR) at week 6, PAR at week 12, PAR at week 24, PAR at week 36, PAR at week 52], safety and cravings appearances.	Every two weeks from week 2 to 12	Yes