Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: the VAPOR-C Trial
- Conditions
- Non Small Cell Lung CancerColonic CancerRectal Cancer
- Interventions
- Registration Number
- NCT04316013
- Lead Sponsor
- Peter MacCallum Cancer Centre, Australia
- Brief Summary
VAPOR-C is a randomised study of the impact of IV versus inhaled anaesthesia (propofol versus sevoflurane) and lidocaine versus no lidocaine on duration of disease free survival inpatients with either colorectal or non small cell lung cancer.
- Detailed Description
VAPOR-C is a pragmatic, event-driven, randomised controlled trial, with a single blind 2x2 factorial design for sevoflurane/propofol and for intravenous lidocaine infusion / no lidocaine infusion.
This trial is designed to test for superiority in disease free survival (DFS) of propofol (total intravenous anaesthesia -TIVA) over sevoflurane (inhalational volatile anaesthesia) and intravenous lidocaine over no lidocaine in patients undergoing surgery for colorectal or non small cell lung cancer (NSCLC). The combination of two cancer types will help address the need to demonstrate the effects of anaesthetic technique across cancers to inform generalisable anaesthesia guidelines. Both NSCLC and colorectal cancer are important for this study due to high incidence rate, many longer-term survivors, and importantly the high risk of local or distant recurrence despite complete surgical resection. In addition, the study will collect additional data in a nested cohort related to the exploratory objectives.
The study aims to recruit 3,500 patients in Australia, New Zealand, Canada, United States and Europe.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 254
- Male or female patients aged 18 years or older at screening
- Has provided written informed consent for the trial
- Patient with American Joint committee on Cancer (AJCC) 8th edition Stage I-III colorectal cancer or Stage I-IIIa NSCLC, as confirmed by histological or cytological diagnosis. In cases where a histological diagnosis is not possible, suspected diagnosis through imaging techniques is acceptable.
- Patient has an American Society of Anaesthesiologists (ASA) score of 1 to 3
- Scheduled to receive elective, surgical resection with curative intent
- Surgery expected to last ≥2 hours and expected to require ≥2 nights hospital stay
- Able to comply with protocol requirements and follow-up procedures
- Confirmed or suspected allergy to propofol, sevoflurane or intravenous lidocaine
- Patient with significant liver disease (with elevated International Normalised Ratio (INR) or bilirubin and/or low albumin; i.e. Childs-Pugh Score >Class A;
- Patient at personal or familial risk of malignant hyperthermia or porphyria
- Patient with a history of other malignancies within the past 5 years. However, patients with malignancies managed with curative therapy and considered to be at low risk of recurrence such as treated skin basal cell carcinoma, squamous cell carcinoma, malignant melanoma ≤1.0mm without ulceration, localised thyroid cancer, cervical carcinoma in situ or prior malignancies with high likelihood of cure (e.g. low grade prostate and breast cancer) may be included in the study
- Patient has distant metastases
- Patient with an actual body weight less than 45kg
- Patients taking the following drugs that are moderate-strong inhibitors of the CYP1A2 and CYP3A4 metabolic pathways within 72 hours prior to surgery: Antibiotics - 'mycin' class: Clarithromycin, Telithromycin, Azithromycin, Erythromycin Antibiotics - 'floxacin' class Ciprofloxacin (exception: can be used preoperatively within a bowel prep regime), Norfloxacin, Levofloxacin, Sparfloxacin Antibiotics - other: Chloramphenicol, Isoniazid Antifungals: Fluconazole, Itraconazole, Ketoconazole, Posaconazole, Voriconazole Antiretrovirals: Atazanavir; Darunavir; Indinavir; Lopinavir; Nelfinavir; Ombitasvir, Paritaprevir, Ritonavir and Saquinavir. Antidepressants/ADHD: Fluvoxamine, Enoxacine. Calcium-channel blockers: Diltiazem, Verapamil Monoclonal Antibodies: Ceritinib, Idelalisib, Lonafarnib, Tucatinib. Other strong cytochrome P450 3A4 inhibitors: Cimetidine, Cobicistat; grapefruit juice, Mifepristone, Nefazodone.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description B Sevoflurane Sevoflurane A Sevoflurane Sevoflurane + intravenous lidocaine A Lidocaine IV Sevoflurane + intravenous lidocaine C Propofol Propofol TIVA + intravenous lidocaine C Lidocaine IV Propofol TIVA + intravenous lidocaine D Propofol Propofol TIVA
- Primary Outcome Measures
Name Time Method Comparison of disease free survival (DFS) with lidocaine compared with no lidocaine Until 3 years from participant index surgery date The study will collect endpoint data for each participant on time of disease progression. This will be used to compare disease free survival across arms.
Comparison of disease free survival (DFS) with propofol-TIVA versus sevoflurane Until 3 years from participant index surgery date The study will collect endpoint data for each participant on time of disease progression. This will be used to compare disease free survival across arms.
- Secondary Outcome Measures
Name Time Method Comparison of overall survival (OS) with propofol-TIVA versus sevoflurane Until 3 years from participant index surgery date The study will collect endpoint data for each participant on survival status. This will be used to compare overall survival across arms.
Days alive and at home with propofol-TIVA versus sevoflurane 30 days post surgery Data will be collected at thirty days post surgery regarding date of discharge from hospital and survival status. This is then used to calculate number of days alive and at home (i.e. out of hospital) and compare across arms.
Overall survival with intravenous lidocaine versus no lidocaine Until 3 years from participant index surgery date The study will collect endpoint data for each participant on survival status. This will be used to compare overall survival across arms.
Days alive and at home with intravenous lidocaine versus no lidocaine 30 days post surgery Data will be collected at thirty days post surgery regarding date of discharge from hospital and survival status. This is then used to calculate number of days alive and at home (i.e. out of hospital) and compare across arms.
Comparison of post-operative complications with intravenous lidocaine versus no lidocaine 5 days post surgery or at discharge if earlier Short term postoperative morbidity assessed by the Post Operative Morbidity Scale (POMS) with Clavien-Dindo severity grading.
POMS is an 18-item tool that addresses nine domains of morbidity relevant to the post-surgical patient . The severity in each POMS domain will then be graded according to the Clavien-Dindo Classification on the basis of treatment applied to correct each respective complication , and captures complications within 5 grades.Safety profile of propofol-TIVA versus sevoflurane during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission Toxicities measured using CTCAE V 5 .0
Concomitant medication use with propofol-TIVA versus sevoflurane 5 days post anaesthesia From 2 weeks prior to surgery up to Day 5 post-surgery administration of relevant medications will be recorded
Comparison of post-operative complications with propofol-TIVA versus sevoflurane 5 days post surgery or at discharge if earlier Short term postoperative morbidity assessed by the Post Operative Morbidity Scale (POMS) with Clavien-Dindo severity grading.
POMS is an 18-item tool that addresses nine domains of morbidity relevant to the post-surgical patient . The severity in each POMS domain will then be graded according to the Clavien-Dindo Classification on the basis of treatment applied to correct each respective complication , and captures complications within 5 grades.Comparison of chronic post surgical pain with propofol-TIVA versus sevoflurane At 90 days and 12 months post surgery Pain measured using the Brief Pain Inventory Short Form. Patient reported pain on a scale of 0 to 10 where 0 is no pain and 10 is worst pain.
Pain measured using the Neuropathic Pain Questionnaire. Patient reported neuropathic pain on a scale of 0 to 100 where 0 is no pain and 100 is worst pain.Safety Profile intravenous lidocaine versus no lidocaine during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission Toxicities measured using CTCAE V 5 .0
Comparison of chronic post surgical pain with intravenous lidocaine versus no lidocaine At 90 days and 12 months post surgery Pain measured using the Brief Pain Inventory Short Form. Patient reported pain on a scale of 0 to 10 where 0 is no pain and 10 is worst pain.
Pain measured using the Neuropathic Pain Questionnaire. Patient reported neuropathic pain on a scale of 0 to 100 where 0 is no pain and 100 is worst pain.Health utility with propofol-TIVA versus sevoflurane At 30 days, 90 days and every 12 months post surgery up to 3 years The EQ-5D-5L is a standardised instrument for use as a measure of health outcome and is applicable to a wide range of health conditions and treatments. This five item scale covers the following dimensions (5D): mobility, self-care, usual activities, pain/discomfort and anxiety/depression, with each dimension having five levels (5L). The use of the EQ-5D-5L will enable utility valuations to be estimated for health states experienced.
Concomitant medications use with intravenous lidocaine versus no lidocaine 5 days post anaesthesia From 2 weeks prior to surgery up to Day 5 post-surgery administration of relevant medications will be recorded
Health utility with intravenous lidocaine versus no lidocaine At 30 days, 90 days and every 12 months post surgery up to 3 years The EQ-5D-5L is a standardised instrument for use as a measure of health outcome and is applicable to a wide range of health conditions and treatments. This five item scale covers the following dimensions (5D): mobility, self-care, usual activities, pain/discomfort and anxiety/depression, with each dimension having five levels (5L). The use of the EQ-5D-5L will enable utility valuations to be estimated for health states experienced
Trial Locations
- Locations (27)
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
The University of Texas MD Anderson Cancer Centre
🇺🇸Houston, Texas, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Mackay Base Hospital
🇦🇺Mackay, Queensland, Australia
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
RedCliffe Hospital
🇦🇺Redcliffe, Queensland, Australia
Rockhampton Hospital
🇦🇺Rockhampton, Queensland, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Ballarat Base Hospital
🇦🇺Ballarat Central, Victoria, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Northern Hospital
🇦🇺Epping, Victoria, Australia
St Vincent's Hospital, Melbourne
🇦🇺Fitzroy, Victoria, Australia
Western Health Footscray Hospital
🇦🇺Footscray, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Goulburn Valley Health
🇦🇺Shepparton, Victoria, Australia
Northeast Health, Wangaratta
🇦🇺Wangaratta, Victoria, Australia
North Shore Hospital
🇳🇿Auckland, New Zealand
Auckland City Hospital
🇳🇿Auckland, New Zealand