Clinical Trial to Evaluate the Efficacy of Smoking Cessation (COMBIVAR)
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).
Drug: Nicotine patches
Drug: Placebo (nicotine patches)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
|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)|
- 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. [ Time Frame: Participants will be followed for the duration of treatment, 12 weeks. ] [ Designated as safety issue: No ]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.
- i) Determine safety of combined therapy (VRN+nicotine patches) versus monotherapy (VRN+placebo patches) [ Time Frame: Every two weeks from week 2 to 12 ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||January 2012|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Varenicline & nicotine patches
Combined therapy by using Varenicline plus nicotine patches.The intervention-phase will comprise two fasses:
Other Name: champixDrug: Nicotine patches
Placebo Comparator: Varenicline & placebo patches
Monotherapy by using Varenicline plus placebo patches.The intervention-phase will comprise two fasses:
Other Name: champixDrug: Placebo (nicotine patches)
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.
|Hospital Universitari de Bellvitge|
|Hospitalet de Llobregat, Barcelona, Spain, 08907|
|Hospital Universitari de Bellvitge|
|L'hospitalet de Llobregat, Barcelona, Spain, 08907|
|Study Director:||JOSEP M RAMON TORRELL, PhD||Hospital Universitari de Bellvitge|