Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: The VAPOR-C Trial
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04316013 |
|
Recruitment Status :
Recruiting
First Posted : March 20, 2020
Last Update Posted : March 23, 2023
|
Sponsor:
Peter MacCallum Cancer Centre, Australia
Collaborators:
National Health and Medical Research Council, Australia
Australian and New Zealand College of Anaesthetists
Victorian Comprehensive Cancer Centre
Information provided by (Responsible Party):
Peter MacCallum Cancer Centre, Australia
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Colonic Cancer Rectal Cancer Non Small Cell Lung Cancer | Drug: Sevoflurane Drug: Propofol Drug: Lidocaine IV | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 3500 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This is an event-driven, international multicentre, randomised controlled trial with a 2x2 factorial design. Patients with stage I-III colorectal cancer or stage I-IIIa NSCLC are eligible and will be randomised in the ratio of 1:1:1:1 using permuted block randomisation with stratification by cancer type (Colon, Rectal or NSCLC), and by site to receive either 1) sevoflurane maintenance anaesthesia and lidocaine infusion or 2) sevoflurane maintenance anaesthesia; or 3), propofol maintenance anaesthesia and lidocaine infusion or 4), propofol maintenance anaesthesia . |
| Masking: | Single (Participant) |
| Masking Description: | The propofol-TIVA/sevoflurane element of each arm will have a single blind (patient blinded), as the administering anesthesiologist cannot be blinded to allocation. The lidocaine infusion or no lidocaine infusion element of each ARM will be blinded to the patient . The anaesthetic team and research team caring for the patient will not be blinded to the lidocaine infusion/no lidocaine infusion element of the randomisation ARM |
| Primary Purpose: | Other |
| Official Title: | Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: The VAPOR-C Trial |
| Actual Study Start Date : | July 31, 2020 |
| Estimated Primary Completion Date : | December 2027 |
| Estimated Study Completion Date : | June 2028 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
| 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 actual body weight and capped at a maximum of 100 kg. |
|
Active Comparator: B
Sevoflurane
|
Drug: Sevoflurane
Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice |
|
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 actual body weight and capped at a maximum of 100 kg. |
|
Active Comparator: D
Propofol TIVA
|
Drug: Propofol
Intravenous anaesthetic used for induction and maintenance of anaesthesia |
Primary Outcome Measures :
- Comparison of disease free survival (DFS) with propofol-TIVA versus sevoflurane [ Time Frame: 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 lidocaine compared with no lidocaine [ Time Frame: 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 :
- Comparison of overall survival (OS) with propofol-TIVA versus sevoflurane [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 post-operative complications with intravenous lidocaine versus no lidocaine [ Time Frame: 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 [ Time Frame: 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.
- Comparison of chronic post surgical pain with intravenous lidocaine versus no lidocaine [ Time Frame: 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 of propofol-TIVA versus sevoflurane [ Time Frame: 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 no lidocaine [ Time Frame: 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 [ Time Frame: 5 days post anaesthesia ]From 2 weeks prior to surgery up to Day 5 post-surgery administration of relevant medications will be recorded
- Concomitant medications use with intravenous lidocaine versus no lidocaine [ Time Frame: 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 propofol-TIVA versus sevoflurane [ Time Frame: 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.
- Health utility with intravenous lidocaine versus no lidocaine [ Time Frame: 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
Other Outcome Measures:
- Comparison of return to intended oncological treatment (RIOT) with propofol-TIVA versus sevoflurane [ Time Frame: At 90 days and 12 months post surgery ]Data will be collected post surgery regarding post treatment adjuvant therapy given according to plan. A comparison will be made between number of participants receiving post surgery oncological treatment as planned 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 no lidocaine [ Time Frame: At 90 days and 12 months post surgery ]Data will be collected post surgery regarding post treatment adjuvant therapy given according to plan. A comparison will be made between number of participants receiving post surgery oncological treatment as planned and the number of patients deviating from the plan in each arm of the study.
- Correlative blood studies [ Time Frame: Preop, Day 1, 3 and 5 (if still an inpatient) and at recurrence ]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.
- Correlative breath biopsy studies [ Time Frame: Preop, Day 1, 3 and 5 (if still an inpatient) and at recurrence ]To characterise the effect of anaesthetic agents on perioperative inflammatory changes will measure Targeted Volatile Organic Compounds of the eicosanoid pathway by sampling patients breath (breath biopsy) to monitor inflammatory changes within the pulmonary compartment.
- MINS Substudy [ Time Frame: Day 0 to day 30 ]
At sites who agree to participate:
Blood Specimens and 12-Lead ECG - 12 Lead ECGS will be done and blood specimens collected to measure Troponin levels at baseline, Day 1 and Day 2 post op.
Assessment of the predefined diagnostic criteria for MINS and perioperative myocardial infarction on Day 5 or Discharge if earlier Assessment of predefined diagnostic criteria for MINS and myocardial infarction at 30 days post op.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04316013
Contacts
| Contact: Bernhard Riedel, MB.ChB | +61385597663 | bernhard.riedel@petermac.org | |
| Contact: Kim Coleman, MN | +61385598318 | Kimberley.Coleman@petermac.org |
Locations
Show 27 study locations
Sponsors and Collaborators
Peter MacCallum Cancer Centre, Australia
National Health and Medical Research Council, Australia
Australian and New Zealand College of Anaesthetists
Victorian Comprehensive Cancer Centre
Investigators
| Principal Investigator: | Bernhard Riedel, MB.ChB | Peter MacCallum Cancer Centre, Australia |
| Responsible Party: | Peter MacCallum Cancer Centre, Australia |
| ClinicalTrials.gov Identifier: | NCT04316013 |
| Other Study ID Numbers: |
18/044 |
| First Posted: | March 20, 2020 Key Record Dates |
| Last Update Posted: | March 23, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
|
Colonic Neoplasms Neoplasms by Site Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Colonic Diseases Lidocaine Propofol Sevoflurane Anesthetics, Local |
Anesthetics Central Nervous System Depressants Physiological Effects of Drugs Sensory System Agents Peripheral Nervous System Agents Anti-Arrhythmia Agents Voltage-Gated Sodium Channel Blockers Sodium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Hypnotics and Sedatives Anesthetics, Intravenous Anesthetics, General Platelet Aggregation Inhibitors Anesthetics, Inhalation |