Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: the VAPOR-C Trial

Phase 3TerminatedNCT04316013

Peter MacCallum Cancer Centre, Australia254 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Enrollment

254

Conditions

Colonic Cancer Rectal Cancer Non Small Cell Lung Cancer

Interventions

SevofluraneDRUG

Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice

PropofolDRUG

Intravenous anaesthetic used for induction and maintenance of anaesthesia

Lidocaine IVDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female patients aged 18 years or older at screening 2. Has provided written informed consent for the trial 3. 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. 4. Patient has an American Society of Anaesthesiologists (ASA) score of 1 to 3 5. Scheduled to receive elective, surgical resection with curative intent 6. Surgery expected to last ≥2 hours and expected to require ≥2 nights hospital stay 7. Able to comply with protocol requirements and follow-up procedures Exclusion Criteria: 1. Confirmed or suspected allergy to propofol, sevoflurane or intravenous lidocaine 2. Patient with significant liver disease (with elevated International Normalised Ratio (INR) or bilirubin and/or low albumin; i.e. Childs-Pugh Score \>Class A; 3. Patient at personal or familial risk of malignant hyperthermia or porphyria 4. 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 5. Patient has distant metastases 6. Patient with an actual body weight less than 45kg 7. 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.

Locations (27)

Cleveland Clinic

Outcomes

Primary Outcomes

Comparison of disease free survival (DFS) with propofol-TIVA versus sevoflurane

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.

Time frame: Until 3 years from participant index surgery date

Comparison of disease free survival (DFS) with lidocaine compared with no lidocaine

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.

Time frame: Until 3 years from participant index surgery date

Secondary Outcomes

Comparison of overall survival (OS) with propofol-TIVA versus sevoflurane

The study will collect endpoint data for each participant on survival status. This will be used to compare overall survival across arms.

Time frame: Until 3 years from participant index surgery date

Days alive and at home with propofol-TIVA versus sevoflurane

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.

Time frame: 30 days post surgery

Overall survival with intravenous lidocaine versus no lidocaine

The study will collect endpoint data for each participant on survival status. This will be used to compare overall survival across arms.

Time frame: Until 3 years from participant index surgery date

Days alive and at home with intravenous lidocaine versus no lidocaine

Data from ClinicalTrials.gov

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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

Prince of Wales Hospital

Randwick, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Mackay Base Hospital

Mackay, Queensland, Australia

RedCliffe Hospital

Redcliffe, Queensland, Australia

Rockhampton Hospital

Rockhampton, Queensland, Australia

...and 17 more locations

Time frame: 30 days post surgery

Comparison of post-operative complications with propofol-TIVA versus sevoflurane

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.

Time frame: 5 days post surgery or at discharge if earlier

Comparison of post-operative complications with intravenous lidocaine versus no lidocaine

Time frame: 5 days post surgery or at discharge if earlier

Comparison of chronic post surgical pain with propofol-TIVA versus sevoflurane

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.

Time frame: At 90 days and 12 months post surgery

Comparison of chronic post surgical pain with intravenous lidocaine versus no lidocaine

Time frame: At 90 days and 12 months post surgery

Safety profile of propofol-TIVA versus sevoflurane

Toxicities measured using CTCAE V 5 .0

Time frame: during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission

Safety Profile intravenous lidocaine versus no lidocaine

Toxicities measured using CTCAE V 5 .0

Time frame: during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission

Concomitant medication use with propofol-TIVA versus sevoflurane

From 2 weeks prior to surgery up to Day 5 post-surgery administration of relevant medications will be recorded

Time frame: 5 days post anaesthesia

Concomitant medications use with intravenous lidocaine versus no lidocaine

From 2 weeks prior to surgery up to Day 5 post-surgery administration of relevant medications will be recorded

Time frame: 5 days post anaesthesia

Health utility with propofol-TIVA versus sevoflurane

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.

Time frame: At 30 days, 90 days and every 12 months post surgery up to 3 years

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