A Phase 4 interventional study of propofol and sevoflurane in Solid Tumor, Carcinoma and Malignancy, sponsored by Hong Kong Children's Hospital. Recruiting at 1 site in Hong Kong. Open to participants aged 6 Months to 18 Years. Per ClinicalTrials.gov, last updated 2022-03-16.
Sponsored by Hong Kong Children's Hospital · Phase 4, Interventional, and Treatment
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.
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.
Patients will also followed up for 3 years for tumor recurrence and disease survival.
Exclusion Criteria:
patients in this group will receive inhalation anaesthesia with sevoflurane at Minimal Alveolar Concentration 0.7-1.3 as the main anaesthetic to achieve Bispectral Index 40-60. Other anaesthetic management will be standardised.
Drug: sevoflurane
patients in this group will receive intravenous propofol using Target Controlled Infusion 'Paedfusor' model 2-5 as the main anaesthetic to achieve Bispectral Index 40-60. Other anaesthetic management will be standardised.
Drug: propofol
intravenous propofol using Target Controlled Infusion 'Paedfusor' model 2-5 as the main anaesthetic to achieve Bispectral Index 40-60
Also known as: Diprivan
sevoflurane at Minimal Alveolar Concentration 0.7-1.3 as the main anaesthetic to achieve Bispectral Index 40-60.
Also known as: ultane, sevorane
difference in Hypoxia Inducible Factor-1 gene expression
pg/mL
Time frame: intraoperative to postoperative 24 hours
difference in levels of Interleukin-6
pg/mL
Time frame: intraoperative to postoperative 24 hours
difference in levels of Tumor Necrosis Factor-alpha
pg/mL
Time frame: intraoperative to postoperative 24 hours
difference in levels of high sensitivity C reaction protein
mg/L
Time frame: intraoperative to postoperative 24 hours
difference in levels of DNA damage (Comet Assay)
%T (percent tail)
Time frame: intraoperative to postoperative 24 hours
difference in levels of Glutathione Peroxidase
μg/mL
Time frame: intraoperative to postoperative 24 hours
difference in levels of Superoxide dismutase
units/ml
Time frame: intraoperative to postoperative 24 hours
difference in levels of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)
ng/mL
Time frame: intraoperative to postoperative 24 hours
difference in levels of 8-oxo-7,8-dihydroguanosine (8-oxoGuo)
ng/mL
Time frame: intraoperative to postoperative 24 hours
difference in the quantity of circulating tumor cells (CTC)
cells/100 µL
Time frame: intraoperative to postoperative 24 hours
cancer free survival at 1 and 3 years
percent
Time frame: intraoperative to postoperative 24 hours
Plan to share: No
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Hong Kong Children's Hospital