Effects of TIVA Versus Inhalational Anaesthesia on Circulating Tumour Cells in Hepatocellular Carcinoma Patients
Effects of Mode of Anaesthesia on Circulating Tumour Cells in Patients Undergoing Inhalational Versus Total Intravenous Anaesthesia for Hepatocellular Carcinoma Surgery : A Randomised Controlled Trial
1 other identifier
interventional
220
1 country
1
Brief Summary
More than 80% of patients with cancer will be exposed to anaesthesia at some point in their treatment. There is increasing evidence that perioperative events, including the type of anaesthesia drugs utilised, have an impact on cancer recurrence and metastases. Although potentially and theoretically curative, surgical resection, manipulation and trauma may disseminate tumour cells and reduce immunity. There have been a number of suggestions as to why cancer may be, paradoxically, worsened by surgery and what methods may be used to mitigate this. One of these is propofol based total intravenous anaesthesia (TIVA), whereby the traditional inhalational anaesthetic drugs are avoided. Commonly used inhalational drugs, such as sevoflurane and desflurane, are pro-inflammatory. Propofol, however, has anti-inflammatory and anti-oxidative properties, induces apoptosis and has specific inhibitory effects on tumour cell growth in vitro. Laboratory investigations, animal models, retrospective clinical studies and initial clinical research are producing evidence that inhalational anaesthesia facilitates tumour recurrence and metastasis, whilst TIVA can prolong survival. This randomised, controlled trial will look at the effects on DNA damage and biomarkers of immunity and inflammation of inhalational anaesthesia versus TIVA in patients undergoing surgery for hepatocellular carcinoma, a common tumour in the Southern Chinese population, for whom surgery is potentially-curative. It will focus on subjects undergoing open and laparoscopic hepatectomy and investigate changes in biomarkers of inflammation, immunity and gene expression from the patients' blood samples taken before, during and after surgery. Patients will also be followed-up for cancer recurrence, morbidity and five-year mortality. Results could represent a breakthrough in knowledge of how anaesthetic agents impact the results of cancer surgery, and have important implications for a more disease- sensitive approach to improving management and outcomes in these patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Mar 2020
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 4, 2020
CompletedFirst Submitted
Initial submission to the registry
September 21, 2020
CompletedFirst Posted
Study publicly available on registry
October 26, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2024
CompletedMarch 31, 2023
February 1, 2023
3.9 years
September 21, 2020
March 28, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
HIF-1 gene expression
the detection of a two-fold difference between the pre-operative blood sample and 24-hour post-operative blood sample in HIF-1 gene expression in the SEVO group, and a less than two-fold difference in the same samples of the TIVA group
24 hour
Secondary Outcomes (9)
Change in number of recurrence
2 year
Level of Gene expression
Pre-operative, Intra-operative, Immediately post-operative and 24 hours post-surgery
Level of DNA damage
Pre-operative, Intra-operative, Immediately post-operative and 24 hours post-surgery
Level of C-reactive protein
Pre-operative, Intra-operative, Immediately post-operative and 24 hours post-surgery
Level of Glutathione Peroxidase
Pre-operative, Intra-operative, Immediately post-operative and 24 hours post-surgery
- +4 more secondary outcomes
Study Arms (2)
SEVO Group
ACTIVE COMPARATORPatients in SEVO group will be anaesthetized by inhalational anaesthesia using sevoflurane.
TIVA group
EXPERIMENTALThe patients in TIVA group will be anaesthetized using total intravenous propofol.
Interventions
Monitoring and other anaesthetic procedures including the management of hypertension and hypotension will be the same as SEVO group. Induction and maintenance of general anaesthesia will be conducted using total intravenous infusion of propofol. Sevoflurane will not be used, and oxygen and air would be given to provide a FiO2 of 30-50%. Target controlled infusion (TCI) with a modified Marsh effect site model (Fresenius Kabi) will be used for induction and maintenance of general anaesthesia and titrated to effect. The usual effect site concentration is 1.5-3 mcg.ml-1 and BIS monitoring will also be used to produce a value of between 40-60. As with patients in the SEVO group, remifentanil will be infused at a rate of between 0.1-0.3 mcg.kg.min-1.
Propofol 1.5-3mg/kg, remifentanil 1mcg/kg, and rocuronium 0.6-1mg/kg or atracurium 0.5mg/kg will be used intravenously for induction of general anaesthesia. Intubation would be performed after induction of general anaesthesia. General anaesthesia monitoring will be used. Sevoflurane, air and oxygen will be used for maintenance of general anaesthesia. FiO2 will be kept between 35-50%. BIS monitoring will be applied and level of anaesthetia will be titrated to maintain a BIS value of between 40-60. Intravenous remifentanil infusion between 0.1-0.2 mcg/kg/min will be given and this will be titrated to provide optimal haemodynamic parameters.
Eligibility Criteria
You may qualify if:
- All patients aged 18-80 years old with primary hepatocellular carcinoma presenting for elective open hepatectomy surgery in Queen Mary Hospital, Hong Kong, will be invited to join this randomised, controlled trial.
You may not qualify if:
- Pre-operative factors
- Contraindication to general anaesthesia
- Autoimmune / Chronic inflammatory diseases e.g. Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis(RA) etc.
- Chemotherapy in the past year
- Steroid therapy
- Surgery for tumour removal in the past year
- patients post liver transplantation Intra-operative factors
- Regional Anaesthesia
- Administration of:
- Nitrous oxide
- Inhalational agents (with the exception of sevoflurane)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
HKU Li Ka Shing Faculty of Medicine
Hong Kong, Guangdong, 999077, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael G. Irwin, M.B. Ch.B
The University of Hong Kong
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Purpose
- HEALTH SERVICES RESEARCH
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 21, 2020
First Posted
October 26, 2020
Study Start
March 4, 2020
Primary Completion
January 31, 2024
Study Completion
March 31, 2024
Last Updated
March 31, 2023
Record last verified: 2023-02
Data Sharing
- IPD Sharing
- Will not share