A Pilot Study Of Smoking Cessation Treatment Including Varenicline In Patients Scheduled For Planned Surgery

Study Overview
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Brief Summary
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It is possible to offer smoking cessation treatment including varenicline to patients scheduled for elective surgery. This study will evaluate whether or not this will enable some patients to quit smoking for up to 4 weeks prior to surgery and in turn, whether this may lead to reductions in post-operative complication such as wound infections.

Detailed Description
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Recruitment to this study was terminated (on February 23, 2010) earlier than originally planned because recruitment was much slower than expected and therefore the study has already achieved its main objective of assessing the feasibility of conducting a larger study of similar design to investigate the efficacy of smoking cessation therapy in a pre-surgical setting. The decision to end recruitment to the trial was not based on any safety concerns.

Official Title
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A Multicenter, Open Label Study To Investigate The Feasibility And Efficacy Of A Smoking Cessation Program With Varenicline In Patients Undergoing Elective Surgery

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Varenicline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smokers motivated to stop smoking scheduled for elective surgery Exclusion Criteria: Current or recent depression Current or recent suicidal ideation Uncontrolled or unstable clinically significant medical condition

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Smoking cessation tratment including varenicline<br> | Drug: Varenicline<br>* Varenicline film coated tablets - escalating dose with maximum dose of 1mg bd<br>* Other names: Champix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Fully Compliant Participants | Compliance defined as completed 12 weeks of varenicline therapy, underwent surgery 8 weeks +-10 days after start of varenicline treatment, and had evaluations of wound infection 1 to 3 days and 6 to 10 days after surgery. | Baseline through Week 12 | 
| Number of Participants With Surgical Site Infection Post-surgery Days 1 to 3: Center for Disease Control (CDC) Definition | Surgical site infections (SSIs) assessed by 1992 CDC definition; divided into incisional and organ/space SSIs. Incisional space SSIs further classified as involving only skin and subcutaneous tissue (superficial incisional) or involving deep soft tissues (fascial and muscle layers) of the incision (deep incisional ). Organ/space SSIs involve any part of the anatomy (organs or spaces) other than incision opened or manipulated during operative procedure. None = did not have a surgical site infection. Category 0 = no surgical wound complications. Not done = not assessed. | Post-surgery Days 1-3 | 
| Number of Participants With Surgical Site Infection Post-surgery Days 6 to 10: Center for Disease Control (CDC) Definition | Surgical site infections (SSIs) assessed by 1992 CDC definition; divided into incisional and organ/space SSIs. Incisional space SSIs further classified as involving only skin and subcutaneous tissue (superficial incisional) or involving deep soft tissues (fascial and muscle layers) of the incision (deep incisional ). Organ/space SSIs involve any part of the anatomy (organs or spaces) other than incision opened or manipulated during operative procedure. None = did not have a surgical site infection. Category 0 = no surgical wound complications. Not done = not assessed. | Post-surgery Days 6-10 | 
| Number of Participants With Surgical Site Infection at Week 12: Center for Disease Control (CDC) Definition | Surgical site infections (SSIs) assessed by 1992 CDC definition; divided into incisional and organ/space SSIs. Incisional space SSIs further classified as involving only skin and subcutaneous tissue (superficial incisional) or involving deep soft tissues (fascial and muscle layers) of the incision (deep incisional ). Organ/space SSIs involve any part of the anatomy (organs or spaces) other than incision opened or manipulated during operative procedure. None = did not have a surgical site infection. Category 0 = no surgical wound complications. Not done = not assessed. | Week 12 | 
| Number of Participants With Surgical Site Infection at Week 26: Center for Disease Control (CDC) Definition | Surgical site infections (SSIs) assessed by 1992 CDC definition; divided into incisional and organ/space SSIs. Incisional space SSIs further classified as involving only skin and subcutaneous tissue (superficial incisional) or involving deep soft tissues (fascial and muscle layers) of the incision (deep incisional ). Organ/space SSIs involve any part of the anatomy (organs or spaces) other than incision opened or manipulated during operative procedure. None = did not have a surgical site infection. Category 0 = no surgical wound complications. Not done = not assessed. | Week 26 | 
| Number of Participants With Surgical Site Infections With Microbiological Confirmation of Bacterial Infection | Microbiological confirmation defined as organisms isolated from an aseptically obtained culture of fluid or tissues from the superficial incision. | Post-surgery Days 1-3, Post-surgery Days 6-10, Week 12, Week 26 | 
| Number of Participants With Grade of Wound Healing and Severity of Surgical Site Infections Post-surgery Days 1 to 3: Southampton Wound Assessment Scale | Grade 0 = normal healing (NH); Grade I = NH with (w) mild bruising (br) or haematoma (a: some br, b: considerable br, c: mild erythema); Grade II= erythema plus other signs of inflammation (a: at 1 point, b: around sutures, c: along wnd, d: around wnd); Grade III= clear or haemoserous discharge (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm, c: large volume, D: prolonged > 3 days); Grade IV= pus (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm; Grade V=deep or severe wnd infection (w or without tissue breakdown; haematoma requiring aspiration). Not done = not assessed. | Post-surgery Days 1-3 | 
| Number of Participants With Grade of Wound Healing and Severity of Surgical Site Infections Post-surgery Days 6 to 10: Southampton Wound Assessment Scale | Grade 0 = normal healing (NH); Grade I = NH with (w) mild bruising (br) or haematoma (a: some br, b: considerable br, c: mild erythema); Grade II= erythema plus other signs of inflammation (a: at 1 point, b: around sutures, c: along wnd, d: around wnd); Grade III= clear or haemoserous discharge (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm, c: large volume, D: prolonged > 3 days); Grade IV= pus (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm; Grade V=deep or severe wnd infection (w or without tissue breakdown; haematoma requiring aspiration). Not done = not assessed. | Post-surgery Days 6-10 | 
| Number of Participants With Grade of Wound Healing and Severity of Surgical Site Infections at Week 12: Southampton Wound Assessment Scale | Grade 0 = normal healing (NH); Grade I = NH with (w) mild bruising (br) or haematoma (a: some br, b: considerable br, c: mild erythema); Grade II= erythema plus other signs of inflammation (a: at 1 point, b: around sutures, c: along wnd, d: around wnd); Grade III= clear or haemoserous discharge (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm, c: large volume, D: prolonged > 3 days); Grade IV= pus (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm; Grade V=deep or severe wnd infection (w or without tissue breakdown; haematoma requiring aspiration). Not done = not assessed. | Week 12 | 
| Number of Participants With Grade of Wound Healing and Severity of Surgical Site Infections at Week 26: Southampton Wound Assessment Scale | Grade 0 = normal healing (NH); Grade I = NH with (w) mild bruising (br) or haematoma (a: some br, b: considerable br, c: mild erythema); Grade II= erythema plus other signs of inflammation (a: at 1 point, b: around sutures, c: along wnd, d: around wnd); Grade III= clear or haemoserous discharge (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm, c: large volume, D: prolonged > 3 days); Grade IV= pus (a: at 1 point only ≤ 2 cm, b: along wnd > 2 cm; Grade V=deep or severe wnd infection (w or without tissue breakdown; haematoma requiring aspiration). Not done = not assessed. | Week 26 | 
| Wound Healing Grade by ASEPSIS Criteria: Post-surgery Days 1 to 3 | Wound grading scale of wound characteristics assessed by portion of wound infected and point scale for daily wound inspection. Infections categorized by ASEPSIS score as satisfactory healing (0-10), disturbance of healing (11-20), minor wound infection (21-30), moderate wound infection (31-40), and severe wound infection (>40). Surgical site complication defined as total score >10; wound infection defined as total score >20. Not done = not assessed. | Post-surgery Days 1-3 | 
| Wound Healing Grade by ASEPSIS Criteria: Post-surgery Days 6 to 10 | Wound grading scale of wound characteristics assessed by portion of wound infected and point scale for daily wound inspection. Infections categorized by ASEPSIS score as satisfactory healing (0-10), disturbance of healing (11-20), minor wound infection (21-30), moderate wound infection (31-40), and severe wound infection (>40). Surgical site complication defined as total score >10; wound infection defined as total score >20. Not done = not assessed. | Post-surgery Days 6-10 | 
| Wound Healing Grade by ASEPSIS Criteria at Week 12 | Wound grading scale of wound characteristics assessed by portion of wound infected and point scale for daily wound inspection. Infections categorized by ASEPSIS score as satisfactory healing (0-10), disturbance of healing (11-20), minor wound infection (21-30), moderate wound infection (31-40), and severe wound infection (>40). Surgical site complication defined as total score >10; wound infection defined as total score >20. Not done = not assessed. | Week 12 | 
| Wound Healing Grade by ASEPSIS Criteria at Week 26 | Wound grading scale of wound characteristics assessed by portion of wound infected and point scale for daily wound inspection. Infections categorized by ASEPSIS score as satisfactory healing (0-10), disturbance of healing (11-20), minor wound infection (21-30), moderate wound infection (31-40), and severe wound infection (>40). Surgical site complication defined as total score >10; wound infection defined as total score >20. Not done = not assessed. | Week 26 | 
| Number of Participants With 7 Day Point Prevalence (PP) for Smoking Abstinence Prior to Hospital Admission. | Responder defined as participant who answered No to question on Nicotine Use Inventory (NUI), Has the subject smoked any cigarettes or cigarillos or used any other nicotine containing products in the last 7 days? Additionally, responder status confirmed by measurement of end-expiratory exhaled carbon monoxide concentration <10 parts per million (ppm). | 7 days prior to hospital admission to day of hospital admission (after Week 8 of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants by Severity of Post-operative Complications: Dindo, Demartines and Clavien Classification System | Grade 0: no post-operative (post-op) complications (comp), Grade 1: any deviation from normal post-op course without need for pharmacological treatment (PT) other than allowed interventions (INT), or surgical, endoscopic or radiological INT; Grade II: required PT with drugs other than those allowed for grade I comp; Grade III required surgical, endoscopic or radiological INT, IIIa: not under general anaesthesia (GA), IIIb: under GA; Grade IV: life-threatening comp requiring IC/ICU management, IVa: single organ dysfunction (DSF), IVb: multiorgan DSF; Grade V: death. Not done = not assessed. | Baseline through Week 26 | 
| Percentage of Participants Who Succeed in Reducing Their Cigarette Consumption by at Least 50% in 7 Days Preceding Hospital Admission Compared With Baseline. |  | Baseline, Week 8 | 
| Number of Participants With 7-day Point Prevalence (PP) for Abstinence From Cigarette Smoking and Other Nicotine Use at the End of Treatment (Week 12) | Responder defined as participant who answered No to question on Nicotine Use Inventory (NUI), Has the subject smoked any cigarettes or cigarillos or used any other nicotine containing products in the last 7 days? Additionally, responder status confirmed by measurement of end-expiratory exhaled carbon monoxide concentration <10 parts per million (ppm). | Week 12 | 
| Number of Participants With 7 Day Point Prevalence (PP) for Abstinence in the Week Preceding Week 26 | Responder defined as participant who answered No to question on Nicotine Use Inventory (NUI), Has the subject smoked any cigarettes or cigarillos or used any other nicotine containing products in the last 7 days? Additionally, responder status confirmed by measurement of end-expiratory exhaled carbon monoxide concentration <10 parts per million (ppm). | Week 26 | 
| Percentage of Participants Who Reduced Their Cigarette Consumption by at Least 50% in the 7 Days Preceding Weeks 12 and 26 Compared With Baseline. |  | Baseline, Week 12, Week 26 | 
| Number of Participants With Treatment-Emergent Adverse Events by Type, Severity, Seriousness, and Relatedness to Varenicline | Treatment-emergent AE (TEAE): any untoward medical occurrence that occurred or worsened after beginning study treatment without regard to causal relationship. Treatment-related TEAE: investigator assessment of reasonable possibility that treatment caused or contributed to AE. Severe TEAE: interfered significantly with usual function. SAE: AE resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience (immediate risk of death), persistent or significant disability/incapacity, congenital anomaly, or deemed significant for any other reason. | Baseline through Week 26 (within 30 days of last dose) | 
| Number of Treatment Emergent Adverse Events by Severity | Mild: did not interfere with usual function; Moderate: interfered to some extent with usual function; Severe: interfered significantly with usual function. If the same participant in a given treatment had more than one occurrence in the same preferred term event category, only the most severe occurrence was taken. Missing baseline severities were imputed as mild. | Baseline through Week 26 (within 30 days of last dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, varenicline, elective surgery, wound infections, post-operative complications