Clinical trial NCT04475705: Propofol vs Sevo for Paediatric Tumor Surgery
Official title: The Effects of Propofol Based Intravenous vs Sevoflurane Inhalation Anaesthesia on Inflammation and Circulating Tumor Cells in Paediatric Tumor Surgery - a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Solid Tumor
Carcinoma
Malignancy
Cancer
Keywords: propofol
sevoflurane
cancer surgery
circulating tumor cells
paediatric
Lead sponsor: Hong Kong Children's Hospital
Sponsor class: OTHER
Collaborators: name: The University of Hong Kong
First posted: 2020-07-17
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single blind controlled trial
Primary purpose: TREATMENT

Brief summary: Background:

Retrospective studies and meta-analyses have shown a reduction in 5-year survival following inhalational based compared to propofol based total intravenous (TIVA) anaesthesia for cancer surgery. To date there have been no prospective trials published which evaluate the effect of anaesthetic technique on circulating tumour cells (CTC), oxidative stress, and recurrence rate following cancer surgery. Children with cancer often require surgery for tumour excision as well as for other diagnostic and therapeutic procedures. To date there has been no prospective randomized controlled trial evaluating the optimal anaesthetic technique for surgery on children with cancer.

Aim:

This is a pilot study in paediatric patients who require surgery for tumour excision. The aim is to investigate the effect of sevoflurane inhalational versus propofol intravenous anaesthesia on expression of hypoxia-inducible factor 1 (HIF-1), circulating tumour cells, DNA damage and biomarkers of immunity and inflammation in patients before and after tumour surgery. The patients will be followed up for up to 5 years for tumour recurrence after surgery.

Method:

This will be a single-blinded randomized controlled trial. One hundred children undergoing tumour excision surgery at the Hong Kong Children's Hospital will be recruited and randomized to receive TIVA or inhalational anaesthesia. Baseline, intraoperative and postoperative blood will be taken for tests of immunity and inflammatory markers, DNA damage and circulating tumour cells. Patients would be followed up to 3 years for tumour recurrence and survival.

Detailed description: Surgical resection is the main modality of treatment for many solid tumors. Despite successful tumor resection, some patients develop local recurrence or metastasis, causing morbidities and mortality. In recent years, there is growing interest in the pathophysiology of recurrence or metastasis. It is believed that the recurrence is caused by the liberation of circulating tumor cells during surgical manipulation of the tumors and the vascular invasive properties of the tumor cells. Perioperative events, such as surgical stress and anaesthesia may have immunomodulating effects, causing growth or inhibition of circulating tumor cells, which affect disease relapse. There is growing evidence that propofol is anti-inflammatory while sevoflurane is pro-inflammatory and their potential roles in cancer recurrence attract researchers' attention. In adults, there is increasing number of researches showing that propofol may improve patient outcomes in terms of disease survival, when compared to sevoflurane. However, such evidence in paediatric population is lacking. This study aims to compare the effects of propofol based intravenous anaesthesia with inhalation anaesthesia with sevoflurane on perioperative biomarkers of inflammation, circulating tumor cells and disease free survival in 3 years.

100 patients will be recruited for this single blinded randomised controlled trial. They will receive general anaesthesia in Hong Kong Children's Hospital for their primary tumor excision surgery. 50 patients will be randomised to sevoflurane group and 50 patients will be randomised to propofol group. They will receive standardised anaesthetic management in terms of death or anaesthesia, pain management, fluid or thermoregulation management. Sevoflurane group subjects will receive inhalational sevoflurane as main anaesthetic, while propofol group subjects will receive intravenous propofol. These patients will have 4 blood tests collected for analysis for biomarkers of inflammation, DNA damage, oxidative stress and circulating tumor cells.

* baseline: once patients have intravenous access established
* intraoperative: when the tumor is deemed resected by surgeons
* immediately postop: after wound closure
* 24 hours postop Early postoperative period follow up will look for wound recovery, sepsis, and time to start chemotherapy and need for second look operation for wound complication.

Patients will also followed up for 3 years for tumor recurrence and disease survival.

Eligibility criteria: Inclusion Criteria:

* patients coming for elective primary solid tumor resection for curative intent in Hong Kong Children's Hospital
* AND patients \> 5kg
* AND patients within age limit

Exclusion Criteria:

* Autoimmune / Chronic inflammatory diseases e.g. Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) etc.
* Current Steroid therapy
* Surgery for tumour removal in the past year
* Allergy to Propofol
* intraoperative use of nitrous oxide
* Patient susceptible to Malignant Hyperthermia
* Patients / parents / legal guardians showing preference in anaesthetic techniques during recruitment process

Primary outcomes:
measure: difference in Hypoxia Inducible Factor-1 gene expression
timeFrame: intraoperative to postoperative 24 hours
Secondary outcomes:
measure: difference in levels of Interleukin-6
timeFrame: intraoperative to postoperative 24 hours
measure: difference in levels of Tumor Necrosis Factor-alpha
timeFrame: intraoperative to postoperative 24 hours
measure: difference in levels of high sensitivity C reaction protein
timeFrame: intraoperative to postoperative 24 hours
measure: difference in levels of DNA damage (Comet Assay)
timeFrame: intraoperative to postoperative 24 hours
measure: difference in levels of Glutathione Peroxidase
timeFrame: intraoperative to postoperative 24 hours
measure: difference in levels of Superoxide dismutase
timeFrame: intraoperative to postoperative 24 hours
measure: difference in levels of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)
timeFrame: intraoperative to postoperative 24 hours
measure: difference in levels of 8-oxo-7,8-dihydroguanosine (8-oxoGuo)
timeFrame: intraoperative to postoperative 24 hours
measure: difference in the quantity of circulating tumor cells (CTC)
timeFrame: intraoperative to postoperative 24 hours
measure: cancer free survival at 1 and 3 years
timeFrame: intraoperative to postoperative 24 hours
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Hong Kong Children's Hospital
Study officials:
affiliation: Hong Kong Children's Hospital
name: Sau Man Lee, MBBS
role: PRINCIPAL_INVESTIGATOR
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