Propofol vs Sevo for Paediatric Tumor Surgery

NCT ID: NCT04475705

Last Updated: 2022-03-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-11
• Study Completion Date: 2028-07-31

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.

Conditions

Solid Tumor; Carcinoma; Malignancy; Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Sevoflurane group

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.

Group Type: ACTIVE_COMPARATOR

sevoflurane

Intervention Type: DRUG

sevoflurane at Minimal Alveolar Concentration 0.7-1.3 as the main anaesthetic to achieve Bispectral Index 40-60.

propofol group

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.

Group Type: ACTIVE_COMPARATOR

propofol

Intervention Type: DRUG

intravenous propofol using Target Controlled Infusion 'Paedfusor' model 2-5 as the main anaesthetic to achieve Bispectral Index 40-60

Interventions

propofol

intravenous propofol using Target Controlled Infusion 'Paedfusor' model 2-5 as the main anaesthetic to achieve Bispectral Index 40-60

Intervention Type: DRUG

sevoflurane

sevoflurane at Minimal Alveolar Concentration 0.7-1.3 as the main anaesthetic to achieve Bispectral Index 40-60.

Intervention Type: DRUG

Other Intervention Names

Diprivan; ultane, sevorane

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: collaborator

Hong Kong Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sau Man Lee, MBBS

Role: PRINCIPAL_INVESTIGATOR

Hong Kong Children's Hospital

Locations

Hong Kong Children's Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Sau Man Lee, MBBS

Role: CONTACT

lsm335@gmail.com

+85257413327

Vivian Yuen, MBBS

Role: CONTACT

yuenmyv@ha.org.hk

+85235133752

Facility Contacts

Rowena Lee

Role: primary

lsm335@ha.org.hk

+85257413327

Vivian Yuen

Role: backup

yuenmyv@ha.org.hk

+85257413131

References

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Reference Type: BACKGROUND

PMID: 24803747 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 23242747 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 20889943 (View on PubMed)

Wigmore TJ, Mohammed K, Jhanji S. Long-term Survival for Patients Undergoing Volatile versus IV Anesthesia for Cancer Surgery: A Retrospective Analysis. Anesthesiology. 2016 Jan;124(1):69-79. doi: 10.1097/ALN.0000000000000936.

Reference Type: BACKGROUND

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Other Identifiers

HKCH-REC-2020-013

Identifier Type: -

Identifier Source: org_study_id