Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: The VAPOR-C Trial
Study Details
Study Description
Brief Summary
VAPOR-C is a randomised study of the impact of IV versus inhaled anaesthesia (propofol versus sevoflurane) and lidocaine versus placebo on duration of disease free survival inpatients with either colorectal or non small cell lung cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
VAPOR-C is a pragmatic, event-driven, randomised controlled trial, with a blinded 2x2 factorial design for sevoflurane/propofol and for intravenous lidocaine/placebo administration.
This trial is designed to test for superiority in disease free survival (DFS) of propofol (total intravenous anaehesia -TIVA) over sevoflurane (inhalational volatile anaesthesia) and intravenous lidocaine over placebo 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 5,736 patients in Australia, New Zealand, Canada, United States and Europe.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: A Sevoflurane + intravenous lidocaine |
Drug: Sevoflurane
Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice
Drug: Lidocaine Iv
1.5mg/kg loading dose over 20 minutes, followed by an infusion of 2mg/kg/hr up to 4 hours and 1.5mg/kg/hour thereafter. Bolus and maintenance dosages of lidocaine will be per adjusted body weight (aBW), to a maximum of 100 kg, actual body weight to be used in patients less than 60kg.
|
| Active Comparator: B Sevoflurane + placebo |
Drug: Sevoflurane
Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice
Other: Placebo
Normal saline
|
| Active Comparator: C Propofol TIVA + intravenous lidocaine |
Drug: Propofol
Intravenous anaesthetic used for induction and maintenance of anaesthesia
Drug: Lidocaine Iv
1.5mg/kg loading dose over 20 minutes, followed by an infusion of 2mg/kg/hr up to 4 hours and 1.5mg/kg/hour thereafter. Bolus and maintenance dosages of lidocaine will be per adjusted body weight (aBW), to a maximum of 100 kg, actual body weight to be used in patients less than 60kg.
|
| Active Comparator: D Propofol TIVA + placebo |
Drug: Propofol
Intravenous anaesthetic used for induction and maintenance of anaesthesia
Other: Placebo
Normal saline
|
Outcome Measures
Primary Outcome Measures
- Comparison of disease free survival (DFS) with propofol-TIVA (DFS) versus sevoflurane [Until 957 endpoint events are reached, estimated at 4 years from study start]
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 lidocaine compared with placebo [Until 957 endpoint events are reached, estimated at 4 years from study start]
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
- Comparison of overall survival (OS) with propofol-TIVA versus sevoflurane [Until 957 endpoint events are reached, estimated at 4 years from study start]
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 placebo [Until 957 endpoint events are reached, estimated at 4 years from study start]
The study will collect endpoint data for each participant on survival status. This will be used to compare overall survival across arms.
- Chronic post surgical pain with intravenous lidocaine versus placebo [90 days 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.
- Chronic post surgical pain with intravenous lidocaine versus placebo [90 days post surgery]
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.
- Days alive and at home with intravenous lidocaine versus placebo [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 propofol-TIVA versus sevoflurane [30 days post surgery]
Short term postoperative morbidity assessed by the Post Operative Morbidity Scale (POMS) with Clavien-Dindo severity grading and Comprehensive Complication Index (CCI) . 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. Assessment of overall morbidity will be captured by the (CCI) , a validated metric for postoperative morbidity ranging from 0 (no complication) to 100 (death) that is designed to differentiate patients having multiple complications from patients having single complications of the same Clavien-Dindo grade. Major organ-specific postoperative complications within 30 days after surgery will be captured, using the recommended definitions published in the consensus statements.
- Comparison of post-operative complications with intravenous lidocaine versus placebo [30 days post surgery]
Short term postoperative morbidity will be assessed by the Post Operative Morbidity Scale (POMS) with Clavien-Dindo severity grading and Comprehensive Complication Index (CCI) . The 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. Assessment of overall morbidity will be captured by the (CCI) , a validated metric for postoperative morbidity ranging from 0 (no complication) to 100 (death) that is designed to differentiate patients having multiple complications from patients having single complications of the same Clavien-Dindo grade. Major organ-specific postoperative complications within 30 days after surgery will be captured, using the recommended definitions published in the consensus statements.
- Comparison of functional capacity with propofol-TIVA versus sevoflurane [90 days post surgery]
Measured by the Duke Activity Status Index (DASI) The DASI is a self-administered questionnaire that measures a patient's functional capacity. Each question has an individual score for YES and a zero score for NO. The sum of the YES replies is entered into a formula to get a rough estimate of a patient's peak oxygen uptake. The higher the sum of YES answers the better higher the oxygen uptake value.
- Comparison of functional capacity with intravenous lidocaine versus placebo [90 days post surgery]
Measured by the Duke Activity Status Index (DASI) The DASI is a self-administered questionnaire that measures a patient's functional capacity. Each question has an individual score for YES and a zero score for NO. The sum of the YES replies is entered into a formula to get a rough estimate of a patient's peak oxygen uptake. The higher the sum of YES answers the better higher the oxygen uptake value.
- Comparison of clinical frailty with propofol-TIVA versus sevoflurane [90 days post surgery]
Measured by the Clinical Frailty Scale (CFS). The CFS is a global score ranging from 1 (very fit) to 9 (terminally ill) to reflect the following domains: disability for basic and instrumental activities of daily living, mobility, activity, energy, and disease-related symptoms.
- Comparison of clinical frailty with intravenous lidocaine versus placebo [90 days post surgery]
Measured by the Clinical Frailty Scale (CFS). The CFS is a global score ranging from 1 (very fit) to 9 (terminally ill) to reflect the following domains: disability for basic and instrumental activities of daily living, mobility, activity, energy, and disease-related symptoms.
- Comparison of acute postoperative pain propofol-TIVA versus sevoflurane [Days 1 - 3 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.
- Comparison of acute postoperative pain intravenous lidocaine versus placebo [Days 1 - 3 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.
- 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.
- Comparison of chronic post surgical pain with propofol-TIVA versus sevoflurane [At 90 days and 12 months post surgery]
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.
- Comparison of chronic post surgical pain with intravenous lidocaine versus placebo [At 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.
- Comparison of chronic post surgical pain with intravenous lidocaine versus placebo [At 12 months post surgery]
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 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
- Safety Profile intravenous lidocaine versus placebo [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]
- Concomitant medications use with intravenous lidocaine versus placebo [5 days post anaesthesia]
- Health utility with propofol-TIVA versus sevoflurane [Through study completion, estimated to be 4 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.
- Health utility with intravenous lidocaine versus placebo [Through study completion, estimated to be 4 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
Other Outcome Measures
- Comparison of return to intended oncological treatment (RIOT) with propofol-TIVA versus sevoflurane [8 to 12 weeks post surgery]
Oncological treatment plan post surgery will be collected prior to surgery and data will be collected post surgery regarding return to this intended plan. A comparison will be made between number of participants receiving post surgery oncological treatment as planned pre-surgery and the number of patients deviating from the plan in each arm of the study.
- Comparison of return to intended oncological treatment (RIOT) with intravenous lidocaine versus placebo [8 to 12 weeks post surgery]
Oncological treatment plan post surgery will be collected prior to surgery and data will be collected post surgery regarding return to this intended plan. A comparison will be made between number of participants receiving post surgery oncological treatment as planned pre-surgery and the number of patients deviating from the plan in each arm of the study.
- Correlative studies [Through study completion, estimated to be 4 years]
Inflammatory markers - Neutrophil to lymphocyte ratio (NLR), Platelet to lymphocyte ratio (PLR), C-reactive protein (CRP) Circulating tumour deoxyribonucleic acid (ctDNA), DNA/RNA, Circulating tumour cells (CTCs), immune profile using flow cytometry and plasma for cytokines These are exploratory transnational research outcomes levels of these biomarkers will be measured over the course of the study and analysed for correlation the study outcomes.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
-
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
-
Patient has an albumin level < 25 g/L
-
Patient has overt clinical heart failure
-
Patients taking the following drugs within 72 hours prior to surgery:
Antibiotics: Clarithromycin, Telithromycin, Azithromycin, Erythromycin, Ciprofloxacin, Norfloxacin, Levofloxacin, Sparfloxacin, Isoniazid, Roxithromycin, Chloramphenicol Antidepressants: Fluvoxamine Calcium-channel blockers: Diltiazem, Nifedipine, Verapamil
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The University of Texas MD Anderson Cancer Centre | Houston | Texas | United States | 77030 |
| 2 | Royal Prince Alfred Hospital | Camperdown | New South Wales | Australia | 2050 |
| 3 | Prince of Wales Hospital | Randwick | New South Wales | Australia | 2031 |
| 4 | Royal Brisbane and Women's Hospital | Herston | Queensland | Australia | 4029 |
| 5 | Gold Coast University Hospital | Southport | Queensland | Australia | 4215 |
| 6 | Princess Alexandra Hospital | Woolloongabba | Queensland | Australia | 4102 |
| 7 | Ballarat Base Hospital | Ballarat Central | Victoria | Australia | 3350 |
| 8 | Box Hill Hospital | Box Hill | Victoria | Australia | 3128 |
| 9 | Footscray Hospital | Footscray | Victoria | Australia | 3011 |
| 10 | Austin Health | Heidelberg | Victoria | Australia | 3084 |
| 11 | Peter MacCallum Cancer Centre | Melbourne | Victoria | Australia | 3000 |
| 12 | The Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
| 13 | Goulburn Valley Health | Shepparton | Victoria | Australia | 3630 |
| 14 | Fiona Stanley Hospital | Murdoch | Western Australia | Australia | 6150 |
| 15 | St John of God Subiaco Hospital | Subiaco | Western Australia | Australia | 6008 |
Sponsors and Collaborators
- Peter MacCallum Cancer Centre, Australia
- National Health & Medical Research Council of Australia (NH&MRC)
- The Australian and New Zealand College of Anaesthetists (ANZCA)
- Victorian Comprehensive Cancer Centre
Investigators
- Principal Investigator: Bernhard Riedel, MB.ChB, Peter MacCallum Cancer Centre, Australia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 18/044