Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001065381
Ethics application status
Approved
Date submitted
5/07/2017
Date registered
21/07/2017
Date last updated
26/05/2022
Date data sharing statement initially provided
25/06/2019
Date results provided
15/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Volatile Anaesthesia and Perioperative Outcomes Related to Cancer (VAPOR-C): A Feasibility Study
Scientific title
Volatile Anaesthesia and Perioperative Outcomes Related to Cancer (VAPOR-C): A Feasibility Study
Secondary ID [1] 292351 0
None
Universal Trial Number (UTN)
U1111-1198-8426
Trial acronym
VAPOR-C Feasibiity
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cancer 303910 0
Condition category
Condition code
Cancer 303276 303276 0 0
Any cancer
Anaesthesiology 303277 303277 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Adult patients scheduled for elective major cancer surgery (breast, lung, prostate, melanoma, colorectal, other), expecting to last 2 or more hours and anticipated to require a minimum of one day in-hospital stay after surgery will be screened for eligibility. Recruited patients will be block randomised by cancer type to receive either volatile anaesthesia or propofol anaesthesia. . Clinicians will deliver propofol via weight-based technique (mg/kg/hour) or via target controlled infusion models (TCI; µg/ml effect or plasma concentration) or titrate volatile anaesthesia at a minimum alveolar concentration (MAC) to attain BIS values in the range of 40-60. FiO2 will be maintained at 40% following induction and the admixture with air titrated to maintain SpO2 >95%.

The volatile anaesthetics to be used in this study are Sevoflurane, Isoflurane and Desflurane. They are all volatile anaesthetics approved for clinical use in Australia and used routinely for induction and maintenance of anaesthesia. Volatile anaesthetic dose is titrated by the treating anaesthetist in response to level of sedation, heart rate, respiratory rate, blood pressure and Bispectoral index monitoring, using a vaporiser connected to an anaesthetic circuit.

Anaesthetists are trained to use both intravenous and inhaled anaesthetic techniques. The decision to use one technique over another is based on multitude of patient, anaesthetic and surgical factors. These include, but are not limited to: patient preference, allergy or contraindication to an agent, history of severe postoperative nausea and vomiting, medical status of patient at time of surgery, availability of equipment to perform TIVA, preference of treating anaesthetist, type, duration and location of surgery. The treating anaesthetist makes an educated decision on which anaesthetic to use for every patient guided by his or her experience and specialist anaesthetic training.
Intervention code [1] 298539 0
Treatment: Drugs
Comparator / control treatment
Propofol is an intravenously administered anaesthetic drug approved for clinical use in Australia and used routinely for induction and maintenance of anaesthesia. Initial bolus of 2-4mg/kg is used for induction followed by maintenance infusion.

Most often, a target controlled infusion pump (TCI) is used to deliver the maintenance infusion using a pre-programmed pharmacokinetic algorithm. If a TCI pump is not available, the infusion is titrated to clinical effect by the treating anaesthetist, and is usually administered in the range of 8-12mg/kg/hr.
Control group
Active

Outcomes
Primary outcome [1] 302662 0
To measure the ability to recruit eligible patients into the study. Criteria: The study protocol will be assessed as feasible if a recruitment rate of at least 75% is achieved.
Timepoint [1] 302662 0
Primary endpoint will be measured at 6 months, or once all patients have been recruited, which ever occurs first.
Primary outcome [2] 302663 0
To measure the ability to successfully deliver each of the two anaesthetic techniques (volatile-based general anaesthesia and TIVA-based anaesthesia) according to the research protocol.
Criteria: The study protocol will be assessed as feasible if a successful delivery rate of at least 90% is achieved.
'Successful delivery' is defined as delivery of the anaesthetic as per treatment arm for the entire operation, without limitation by correct equipment, or perioperative event indicating change from one anaesthetic technique to the other'.
Timepoint [2] 302663 0
Primary endpoint will be measured at 6 months, or once all patients have been recruited, which ever occurs first.
Secondary outcome [1] 336705 0
To measure the ability to capture the emerging key performance indicator ‘ Return to Intended Oncologic Therapy (RIOT; i.e. planned date for postoperative adjuvant therapy).
Criteria: All patient records will be screened for details of planned postoperative oncological therapy and planned date of commencement. the following outcomes will be measured:
• Percentage RIOT achieved on time

To be calculated by 'number of patients who achieved RIOT by the date determined pre-operatively by treating oncology team' / ' total number of patients who achieved RIOT'.
Timepoint [1] 336705 0
Variable. Expected to be 6-8 weeks post-operatively.
Secondary outcome [2] 336911 0
• Percentage RIOT delayed
To be calculated by 'number of patients who achieved RIOT but WITH delay' / ' total number of patients who achieved RIOT'.
Delay is defined as an actual start date for postoperative chemo-radiotherapy DIFFERENT to planned start date as determined and recorded by treating oncology team.
Timepoint [2] 336911 0
Variable - expected time point 6-8 weeks post date of surgery
Secondary outcome [3] 336912 0
• Percentage RIOT failed.
Defined by 'number of patients that were planned for adjuvant chemotherapy but who DID NOT achieve RIOT / 'number of patients that were intended to have postoperative adjuvant therapy as determined by the treating oncology team
Timepoint [3] 336912 0
variable - average of 6-8 weeks post-date of surgery
Secondary outcome [4] 336913 0
• Reasons for delayed or failed RIOT
Descriptive data on reasons for failure to achieve RIOT (eg, death, sepsis, neutropaenia, organ impairment/failure, progression of disease, surgical complication)
-This outcome will be assessed by review of patient medical records
Timepoint [4] 336913 0
Variable. 6-8 post-date of surgery
Secondary outcome [5] 336914 0
To test the feasibility of using routine administrative cost data to determine differences in health system costs and government funding for the two study groups.
Timepoint [5] 336914 0
Secondary endpoint will be measured at 6 months, or once all patients have been recruited, which ever occurs first.
Secondary outcome [6] 336915 0
Days alive and out of hospital (DAOH) at 30 days post-surgery, which incorporates mortality and all hospitalizations into a single measure.
-outcome to be assessed by review of medical records
Timepoint [6] 336915 0
30 days post-surgery

Eligibility
Key inclusion criteria
1. Male or female
2. Age 18-80 years.
3. Elective surgery
4. Major cancer surgery expecting to last two or more hours, for:
Breast (mastectomy or segmentectomy PLUS sentinel node dissection),
Colorectal,
Lung,
Prostate,
Melanoma (excision of melanoma PLUS lymph node dissection AND/OR skin flap construction, or
Other major cancer surgeries (e.g. oesophagectomy, head and neck cancer, etc.)
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Palliative surgery for end-stage disease with no curative intent
2. Emergency surgery
3. Extensive co-morbid disease, i.e. ASA >4
4. Refusal or inability to provide valid informed consent
5. Risk of severe postoperative nausea and vomiting (PONV risk score >3)
6. Previous allergy or contraindication to either anaesthetic medication
7. Indication for gas induction of anaesthesia

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be randomised by someone otherwise not involved in the study, to limit selection bias. Participants will be randomized via a central computer-generated randomization program with direct notification to the treating anaesthetist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1. Block randomisation by cancer type.
2. Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis
The feasibility study requires a total of 200 participants that meet inclusion and exclusion criteria to be recruited from the participating hospitals. If 75% of eligible patients are found to provide conformed consent (150/200), then the 95% CI of the true underlying informed consent rate is [68%, 81%]. Assuming 75 patients are recruited to each arm, then if a successful delivery rate of 91% is observed (68/75), then the 95% CI of the true underlying successful delivery rate is [82%, 96%], using and exact (Clopper-Pearson) method to measure the 95% confidence intervals. In this feasibility study, statistical analysis will be primarily descriptive and testing (if any) will be reported with caution. Descriptive statistics will consist of number and percentage for categorical variables. Mean and standard deviation (SD) or median and interquartile range (IQR) will be reported for continuous variables. The asymptotic [Wald] method based on the normal approximation for the two-sided 95% confidence interval for a single proportion will be used toobtain the confidence interval for the proportion of eligible patients who provided informed consent (primary aim 1) and the proportion of randomized patients for whom the anaesthetic procedure was completed successfully, for each procedure separately (primary aim 2). Successful delivery of anaesthetic technique will be defined as a patient undergoing surgery under assigned anaesthetic group, without crossover to other anaesthetic technique during the operation. Reasons for failure to successfully deliver anaesthetic technique may include lack ofaccess to TCI pump to deliver propofol anaesthetic, or crossover to other anaesthetic technique for medical reasons, as determined by treating anaesthetist. Initial estimates of cost-effectiveness will also be available to inform design of the VAPOR-C trial and provide an indication of the likely cost benefits.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/07/2017
Actual
1/08/2017
Date of last participant enrolment
Anticipated
30/09/2019
Actual
21/08/2019
Date of last data collection
Anticipated
1/01/2020
Actual
21/08/2020
Sample size
Target
200
Accrual to date
Final
169
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8484 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 8485 0
The Alfred - Prahran
Recruitment hospital [3] 8486 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 19001 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 16571 0
3000 - Melbourne
Recruitment postcode(s) [2] 16572 0
3004 - Prahran
Recruitment postcode(s) [3] 16573 0
3084 - Heidelberg
Recruitment postcode(s) [4] 33543 0
3050 - Parkville
Recruitment outside Australia
Country [1] 23564 0
United States of America
State/province [1] 23564 0
Texas

Funding & Sponsors
Funding source category [1] 296908 0
Charities/Societies/Foundations
Name [1] 296908 0
Australian and New Zealand College of Anaesthetists
Country [1] 296908 0
Australia
Funding source category [2] 296921 0
Other
Name [2] 296921 0
Melbourne Clinical and Translational Science Platform
Country [2] 296921 0
Australia
Funding source category [3] 296922 0
Hospital
Name [3] 296922 0
Department of Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre
Country [3] 296922 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre Office of Cancer Research
Address
Peter MacCallum Cancer Centre
305 Grattan St, Parkville, VIC, 3000
Country
Australia
Secondary sponsor category [1] 295926 0
None
Name [1] 295926 0
None
Address [1] 295926 0
N/A
Country [1] 295926 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298118 0
Peter MacCallum Cancer Centre Ethics Commitee
Ethics committee address [1] 298118 0
Ethics committee country [1] 298118 0
Australia
Date submitted for ethics approval [1] 298118 0
22/12/2016
Approval date [1] 298118 0
26/04/2017
Ethics approval number [1] 298118 0
HREC/16/PMCC/171

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76054 0
Prof Bernhard Riedel
Address 76054 0
Department of Anaesthesia, Perioperative and Pain Medicine
Peter MacCallum Cancer Centre
305 Grattan St, Parkville, VIC, 3000
Country 76054 0
Australia
Phone 76054 0
+61 3 8559 7681
Fax 76054 0
Email 76054 0
[email protected]
Contact person for public queries
Name 76055 0
Sam McKeown
Address 76055 0
Department of Anaesthesia, Perioperative and Pain Medicine
Peter MacCallum Cancer Centre
305 Grattan St, Parkville, VIC, 3000
Country 76055 0
Australia
Phone 76055 0
+61 3 8559 5000
Fax 76055 0
Email 76055 0
[email protected]
Contact person for scientific queries
Name 76056 0
Bernhard Riedel
Address 76056 0
Department of Anaesthesia, Perioperative and Pain Medicine
Peter MacCallum Cancer Centre
305 Grattan St, Parkville, VIC, 3000
Country 76056 0
Australia
Phone 76056 0
+61 3 8559 7681
Fax 76056 0
Email 76056 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePerioperative events influence cancer recurrence risk after surgery.2018https://dx.doi.org/10.1038/nrclinonc.2017.194
Dimensions AIAnesthetics or anesthetic techniques and cancer surgical outcomes: A possible link2021https://doi.org/10.4097/kja.20679
N.B. These documents automatically identified may not have been verified by the study sponsor.