Smoking CessationPhase 4COMBIVARNCT01538394
Clinical Trial to Evaluate the Efficacy of Smoking Cessation
A Phase 4 study testing Varenicline and Nicotine patches in people with Smoking Cessation, run by Josep Maria Ramon Torrell, PhD at 1 site in Spain.
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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Smoking Cessation
- What is being tested?
- Varenicline and Nicotine patches
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 322 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2012to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
About this study
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)
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).
Read the 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.
- Conditions
- Smoking Cessation
- Being tested
- Varenicline, Nicotine patches, Placebo (nicotine patches)
- Keywords
- smoking cessation, abstinence, clinical trial, varenicline, nicotine
- Medical subject headings
- Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VareniclineDrug
Also called champix
Nicotine patchesDrug
Also called Campix, Nicotinell
Placebo (nicotine patches)Drug
| Study group | Role | What they receive |
|---|---|---|
| Varenicline & nicotine patches | Experimental | 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. Receives: Drug: Varenicline; Drug: Nicotine patches |
| Varenicline & placebo patches | Placebo comparator | 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. Receives: Drug: Varenicline; Drug: Placebo (nicotine patches) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Participants will be followed for the duration of treatment, 12 weeks.
Secondary outcomes (1)
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.
Measured: Every two weeks from week 2 to 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2012 (estimated)
- Study startJan 2012
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 322 participants (actual)
Sponsor and investigators
- Lead sponsor
- Josep Maria Ramon Torrell, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Josep Maria Ramon Torrell, PhD, Hospital Universitari de Bellvitge
- Investigators
- JOSEP M RAMON TORRELL, PhD, Study director, Hospital Universitari de Bellvitge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01538394
- Sponsor's protocol ID
- VAR/01/011
- Acronym
- COMBIVAR
- Status last verified
- Oct 2013
- First submitted
- 14 Feb 2012
- Last updated
- 18 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.
PubMed 37142273Ramon JM, Morchon S, Baena A, Masuet-Aumatell C. Combining varenicline and nicotine patches: a randomized controlled trial study in smoking cessation. BMC Med. 2014 Oct 8;12:172. doi: 10.1186/s12916-014-0172-8.
PubMed 25296623
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01538394
- Acronym / sponsor ID
- COMBIVAR / VAR/01/011
- Conditions
- Smoking Cessation
- Keywords
- smoking cessation, abstinence, clinical trial, varenicline, nicotine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 322 participants (actual)
- Lead sponsor
- Josep Maria Ramon Torrell, PhDUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 24 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Varenicline & nicotine patches | Experimental | Drug: Varenicline, Drug: Nicotine patchesCombined 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. |
| Varenicline & placebo patches | Placebo comparator | Drug: Varenicline, Drug: Placebo (nicotine 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VareniclineAlso: champix | Drug | Varenicline & nicotine patches, Varenicline & placebo patches |
| Nicotine patchesAlso: Campix, Nicotinell | Drug | Varenicline & nicotine patches |
| Placebo (nicotine patches) | Drug | Varenicline & placebo patches |
Primary outcome
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.
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.
1 secondary outcome
i) Determine safety of combined therapy (VRN+nicotine patches) versus monotherapy (VRN+placebo patches)
Time frame: Every two weeks from week 2 to 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2013.
- Derived from this study: PubMed 37142273Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.
- Derived from this study: PubMed 25296623Ramon JM, Morchon S, Baena A, Masuet-Aumatell C. Combining varenicline and nicotine patches: a randomized controlled trial study in smoking cessation. BMC Med. 2014 Oct 8;12:172. doi: 10.1186/s12916-014-0172-8.
Related trials for Smoking Cessation
Enrolling by invitationObservational study
Using Smartwatches to Monitor Smoking in Real-life Situations
Smoking
Not yet recruitingObservational study
PROMETHEE: A Shared Interregional Tele-Tobacco Cessation Platform Embedded Within the IMPULSION Lung Cancer Screening Program
Smoking Cessation, Lung Cancer Screening
Not yet recruiting
Impacto 2.0: Mobile Smoking Cessation Across Texas
Cigarette Smoking, Smoking Cessation
Not yet recruiting
Smoking Cessation Program for Lao People With HIV
Smoking Cessation, HIV
RecruitingPhase 3
Studying NMDA and Sigma-1 in Smoking Cessation Treatment (SUMMIT)
Smoking Cessation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
JOSEP M RAMON TORRELL, PhD study director
Hospital Universitari de Bellvitge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Varenicline and Nicotine patches in people with Smoking Cessation, run by Josep Maria Ramon Torrell, PhD at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01538394, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2013.