Clinical Trial to Evaluate the Efficacy of Smoking Cessation (COMBIVAR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Josep Maria Ramon Torrell, PhD, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:
NCT01538394
First received: February 14, 2012
Last updated: October 17, 2013
Last verified: October 2013
  Purpose

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).


Condition Intervention Phase
Smoking Cessation
Drug: Varenicline
Drug: Nicotine patches
Drug: Placebo (nicotine patches)
Phase 4

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Hospital Universitari de Bellvitge:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 322
Study Start Date: January 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Varenicline & nicotine patches

Combined therapy by using Varenicline plus nicotine patches.The intervention-phase will comprise two fasses:

  • Pre-NRT: Patients take 1 week VRN impregnation (0.5mg/day during the first 3 days + 0.5mg twice daily for the next for days)
  • Treatment: starting at day 8 and during the next 11 weeks patients continue taking VRN 1mg twice daily plus placebo transdermal patches of 30cm2/24 hours per 8 weeks and then 20cm2/24 hours per 3 weeks.
Drug: Varenicline
Other Name: champix
Drug: Nicotine patches
Other Names:
  • Campix
  • Nicotinell
Placebo Comparator: Varenicline & placebo patches

Monotherapy by using Varenicline plus placebo patches.The intervention-phase will comprise two fasses:

  • Pre-NRT: Patients take 1 week VRN impregnation (0.5mg/day during the first 3 days + 0.5mg twice daily for the next for days)
  • Treatment: starting at day 8 and during the next 11 weeks patients continue taking VRN 1mg twice daily plus nicotine transdermal patches of 30cm2/24 hours per 8 weeks and then 20cm2/24 hours per 3 weeks.
Drug: Varenicline
Other Name: champix
Drug: Placebo (nicotine patches)

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01538394

Locations
Spain
Hospital Universitari de Bellvitge
Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Universitari de Bellvitge
L'hospitalet de Llobregat, Barcelona, Spain, 08907
Sponsors and Collaborators
Josep Maria Ramon Torrell, PhD
Investigators
Study Director: JOSEP M RAMON TORRELL, PhD Hospital Universitari de Bellvitge
  More Information

No publications provided

Responsible Party: Josep Maria Ramon Torrell, PhD, Josep Maria Ramon Torrell, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier: NCT01538394     History of Changes
Other Study ID Numbers: VAR/01/011
Study First Received: February 14, 2012
Last Updated: October 17, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Hospital Universitari de Bellvitge:
smoking cessation
abstinence
clinical trial
varenicline
nicotine

Additional relevant MeSH terms:
Nicotine
Varenicline
Autonomic Agents
Cholinergic Agents
Cholinergic Agonists
Ganglionic Stimulants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014