| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10053325 |
| E.1.2 | Term | Smoking cessation therapy |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
- Assess the feasibility of conducting a multicentre prospective trial involving smoking cessation treatment, pre-planned and scheduled surgery and collection of data on surgical site infections and other post-operative complications.
- Generate data on rates of surgical site infections and other post-operative complications in patients undergoing elective orthopaedic, plastic, general and vascular surgery.
- Assess the practicality and utility of three separate instruments in recording data on surgical site infection and in assessing and grading surgical site infections and of a further instrument in grading other post-operative complications.
- Assess the efficacy of Varenicline and smoking cessation advice to enable cessation of smoking for the 7 day period preceding hospital admission in patients undergoing elective surgery.
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| E.2.2 | Secondary objectives of the trial |
- Assess the efficacy of Varenicline and smoking cessation advice to enable smoking cessation at other time points in patients scheduled for elective surgery.
- Assess the efficacy of Varenicline and smoking cessation advice to enable patients to reduce the number of cigarettes or cigarillos they smoke by >50% in the 7 days preceding hospital admission compared with baseline.
- Assess the efficacy of Varenicline and smoking cessation advice to enable smoking reduction at other time points in patients scheduled for elective surgery.
- Assess the safety and tolerability of a 12-week course of Varenicline in patients scheduled for elective surgery.
- Enable exploratory analyses of the influence of smoking cessation on post- operative outcomes; in particular to evaluate the optimal timing of smoking cessation prior to surgery in relation to wound healing.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have evidence of a personally signed and dated informed consent document indicating that the subject (or legally acceptable representative) has understanding of all aspects of the study.
2. Male or female cigarette or cigarillo smokers aged 18 or over who are motivated to stop smoking before surgery.
3. Subjects must have smoked an average of at least 10 cigarettes or cigarillos per day during the past year, with no period of abstinence greater than 3 months in the past year. (Subjects who only smoke cigars and/or pipes are not eligible.)
4. Subjects must have smoked an average of at least 10 cigarettes or cigarillos per day over the month prior to the screening visit.
5. Subjects must be due to undergo planned elective surgery: orthopaedic (eg, elective hip or knee joint replacement) or plastic surgery (eg, abdominoplasty) or general surgery (eg, cholecystecomy, partial thyroidectomy, hernia repair) or vascular surgery (eg, carotid endarterectomy). Surgery should be scheduled to start at 8 weeks +/-10 days after the start of study drug treatment.
6. Subjects where the elective surgery is expected to produce a scar at least 3 cms long (or if there is more than one scar, the combined length of the scars is expected to be at least 3 cms long).
7. Subjects willing to return to hospital between 1-3 days post-surgery and between 6-10 days post-surgery for assessment of wound healing (or the expected period of hospitalisation covers these time periods).
8. If female, be not of childbearing potential (ie, surgically sterile or postmenopausal for at least two years), or be non-pregnant and using an acceptable method of birth control (such as implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner) for a least one month prior to the screening visit if necessary, and for the duration of the study period. Subject must also agree not to breastfeed for the duration of the study period.
9. Subjects must be likely to comply with the protocol, scheduled visits, laboratory tests and medication regimen. |
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| E.4 | Principal exclusion criteria |
1. Subjects for whom the planned surgical procedure is anticipated to cause marked suppression of gastro-intestinal activity lasting greater than 24 hours.
2. Subjects who have an uncontrolled, unstable clinically significant medical condition (eg, renal, hepatic, endocrine, respiratory, cardiovascular, haematologic, immunologic, cerebrovascular disease, or malignancy), which, in the opinion of the investigator, may render them unsuitable for the study and/or interfere with the interpretation of safety or efficacy evaluations. Diabetic subjects may be included in the study if their condition is stable and they satisfy anaesthetic criteria. Patients with renal impairment may be included in the study if the impairment is not severe.
3. Subjects currently suffering with depression, or who have been diagnosed with depression or treated with an anti-depressant for their depression within the past 12 months. Subjects should be excluded if their score at the screening or baseline administration of the Patient Health Questionnaire (PHQ-9) is ≥5, or if they have a score of >0 on item 9 regarding suicidal ideation or behaviour.
4. Subjects with any history of suicidal ideation or suicidal behaviour as assessedby the Columbia Suicide-Severity Rating Scale (C-SSRS; Baseline Version) in the past 12 months, or at the time of the Baseline Visit.
5. Subjects with a past or present history of psychosis; subjects who have experienced anxiety disorders (including anxiety attacks) and bipolar disorder over the past 12 months or who are receiving treatment for these disorders.
6. Subjects with newly diagnosed or uncontrolled hypertension (eg, systolic blood pressure > 150 mmHg or diastolic blood pressure > 95 mmHg at screening/baseline) requiring new treatment or changes in treatment to bring blood pressure under control.
7. Subjects with evidence or history of serious or life-threatening allergic reactions to drugs (for example anaphylaxis or Stevens-Johnson syndrome).
8. Subjects with a history of drug (except nicotine) or alcohol abuse or dependence within the past 12 months.
9. Subjects receiving concomitant treatment with another investigational drug within 30 days of the study baseline visit or with plans to take another investigational drug within 30 days of study completion.
10. Subjects who are receiving or have received any other pharmacotherapy for smoking cessation (eg, bupropion or nicotine replacement therapy) or have started significant nondrug therapy (eg, hypnotherapy or acupuncture) for smoking cessation within the last 4 weeks.
11. Subjects who do not agree to completely abstain from using noncigarette/ cigarillo tobacco products (including, for example, pipe tobacco, cigars, snuff, nicotine replacement therapy, etc.) during study participation.
12. Subjects who donate blood or blood components while receiving study drug or within 1 month of the completion of the study treatment.13. Subjects unable and/or unlikely to comprehend and follow the study protocol, including subjects unable and/or unwilling to participate in the non-treatment follow up.
14. Subjects who in the investigator’s opinion will be unlikely to commit to the study.
15. Subjects with any other contraindication listed in the SmPC including hypersensitivity to Varenicline or to any of the excipients. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
- Percentage of subjects who complete 12-weeks of Varenicline therapy, undergo surgery in the pre-specified period of 8 weeks ±10 days after start of Varenicline treatment, and who have evaluations of wound infections during the pre-specified time windows (1-3 and 6-10 days after surgery).
- Incidence of surgical sites diagnosed with infection (1992 CDC definition).
- Incidence of surgical site infections where there is microbiological confirmation of bacterial infection.
- Grading of wound healing and severity of surgical site infections (Southampton Wound Assessment scales).
- Grading of wound healing by ASEPSIS.
- Incidence and severity of post-operative complications classified according to the system developed by Dindo, Demartines and Clavien.
- 7 day point prevalence (PP) for abstinence prior to hospital admission.
- Proportion of subjects who succeed in reducing their cigarette consumption by at least 50% in 7 days preceding hospital admission compared with baseline.
- 7-day point prevalence (PP) for abstinence from cigarette smoking and other nicotine use at the end of treatment (Week 12). Subjects will be classified as responders if they are able to maintain complete abstinence from cigarette smoking and other nicotine use for the last week of planned treatment confirmed with end- xpiratory exhaled CO measurements <10 ppm.
- 7 day point prevalence (PP) for abstinence in the week preceding the study visits at week 26.
- Proportion of subjects who succeed in reducing their cigarette consumption by at least 50% in the 7 days preceding weeks 12 and 26 compared with baseline.
- Type, severity, seriousness, and relatedness to Varenicline treatment of all reported adverse events. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 3 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 17 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 17 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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