Effect of TIVA Propofol vs Sevoflurane Anaesthetic on Serum Biomarkers and on PBMCs in Breast Cancer Surgery

December 15, 2023 updated by: Dr. J. V. Divatia, Tata Memorial Centre

A Prospective, Randomized, Controlled Trial to Compare the Effect of TIVA Propofol vs Sevoflurane Anaesthetic on Serumserum Biomarkers and on PBMCs in Patients Undergoing Breast Cancer Resection Surgery

Surgery, perioperative stress, anaesthetics and analgesics may modulate the immunosurveillance mechanisms and overwhelm host defences that normally maintain a balance between immunity & carcinogenesis. This may lead to escape of cancer cells and tilt the scales toward a more protumorigenic microenvironment. Volatile agents, in particular, have been shown to exhibit profound immunosuppressive effects. In comparison, propofol has a favorable profile and inhibits cancer cell activity. Determining "cancer-protective" role of TIVA with propofol presents an exciting window of opportunity that has potential to improve outcomes in cancer patients undergoing resection surgery

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

For the current study, consenting patients planned for upfront surgery, will be randomly allocated to 2 groups- 20 patients each group: Propofol TCI-based Total Intravenous Anesthesia group (Propofol group) and Sevoflurane group (Sevoflurane group), according to computer generated randomization number.

Patients will be monitored routinely with ECG, non invasive blood pressure, and a pulse- oximetery (SPO2), every 5 min. An intravenous access will be established with 20- 22 G cannula. A perioperative antibiotic prophylaxis will be given to all patients. None of the patients will receive any premedication.

After preoxygenation with 100% O2 for 3 min: group specific separate interventions will be performed.

Patient will be ventilated with TV of 6-8ml/kg,respiratory rate will be adjusted to maintain end-tidal CO2 value between 40 - 45 mmHg. Crystalloids will be used for hydration (4-6 ml/kg/h), and intraoperative volume deficits will be replaced by additional administration of a solution according to clinical needs. For TIVA group, the depth of anaesthesia will be monitored using Bispectral Index, with target BIS value between 40 and 60. For Sevoflurane group, the depth of anaesthesia will be monitored using MAC, with target MAC value between 0.8 and 1. Half hour before conclusion of surgery, all patients will receive 0.1mg/kg of ondansetron as prophylaxis for PONV. At the end of surgery, muscle relaxation will be reversed by glycopyrrolate (10mcg/kg) and neostigmine (50mcg/kg).

Patients in both groups will receive intra-venous non-steroidal anti-inflammatory drug 1-1.5mg/kg diclofenac + Paracetamol 1gm just before conclusion of surgery for postoperative analgesia. Postoperative pain & PONV will be managed as per institutional protocols.

ASSAY Peripheral blood (5ml) will be collected from patients in EDTA vaccutainer and (5ml) in another vaccutainer containing clot activator. The sample will be collected at following time points.

  1. before anaesthesia (Tpre)
  2. after removal of tumor intraoperative (Ti)
  3. 2 h after surgery (T2h) , and
  4. (T24h) 24 hours after surgery

Estimation of serum cytokines : by sandwich ELISA and by cytokine bead array (CBA) method.

Expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, γδT cells, NK cells and B cells) by flow cytometry

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • India
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Tata Memorial Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Women with histopathologically (biopsy/FNAC) proven breast carcinoma with Resectable disease (T 1-4, N 0-1, M 0) [Stage I-III].
  2. Willing for upfront modified radical mastectomy.
  3. ASA Physical Status 1-2

Exclusion Criteria:

  1. use of morphine or on steroid therapy upto 3 months before surgery;
  2. history of substance abuse or cognitive dysfunction;
  3. endocrine disorders- diabetes, hypothyroid;
  4. history of HIV, Hep-B or Hep-C infections;
  5. Contraindication to analgesics or anaesthetic drugs;
  6. Pregnant & lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Fluoromethyl hexafluoroisopropyl ether
In Sevoflurane group, anaesthesia will be induced with Thiopental 5 - 7mg/kg, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with sevoflurane 2-2.2 % to maintain a target MAC value between 0.8 & 1.0.
Drug: Fluoromethyl hexafluoroisopropyl ether
In Sevoflurane group, anesthesia will be induced with 5 - 7mg/kg thiopental, maintenance with O2 with air 50:50%, sevoflurane 2-2.5 %, Further fentanyl, in increments of 1 mcg/kg - and atracurium 0.15 mg/kg, will be given as indicated by the clinical signs and hemodynamic changes.
Other Names:
  • Sevoflurane
Drug: Fentanyl Citrate
Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.
Other Names:
  • Verfen 100mcg/2ml, Verve
Drug: Atracurium Besylate
Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement
Other Names:
  • Atrapure 25mg/2.5ml, Samarth Life Sciences Pvt. Ltd.
Experimental: 2,6 diisopropylphenol
In Propofol group, anesthesia will be will be induced with Propofol TCI [target controlled infusion pump - Injectomat® TIVA Agilia (Fresenius Kabi)] using Schneider model to achieve target site concentration of 4-6mcg/ml, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with TCI propofol at 3 - 6 mcg/ml as effect site concentration to maintain BIS 40-60.
Drug: Fentanyl Citrate
Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.
Other Names:
  • Verfen 100mcg/2ml, Verve
Drug: Atracurium Besylate
Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement
Other Names:
  • Atrapure 25mg/2.5ml, Samarth Life Sciences Pvt. Ltd.
Drug: 2,6-Diisopropylphenol
In Propofol group, anesthesia will be induced with Propofol TCI using Schneider model to achieve a target site concentration of 4 - 6 mcg/ml. Propofol TCI to achieve BIS (Bispectral Index) between 40-60.
Other Names:
  • Fresofol 1%, Fresenius Kabi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in baseline levels versus 24 hour postoperative levels (Tpre vs T24h ) of serum HIF-1a and VEGF-C in both groups.
Time Frame: Baseline levels versus 24 hour postoperative levels (Tpre vs T24h )
The primary objective of this study is to compare the potential effects of inhalation anesthetic (Sevoflurane) with intravenous anesthetic agent (Propofol) on preoperative levels versus 24hour postoperative levels (Tpre vs T24h ) of serum Hypoxia Inducible Factor-1 alpha (HIF-1a) and Vascular Endothelial Growth Factor -C (VEGF-C) in patients with breast cancer undergoing resection surgery.
Baseline levels versus 24 hour postoperative levels (Tpre vs T24h )

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in levels of serum biomarkers TGF-β, IL-17 IFN-g, TNF-a, IL-6 and MMP-2 at the four time points in both groups.
Time Frame: preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.
Transforming Growth Factor -beta (TGF-β), Interleukin - 17 (IL-17), Inferferon - gamma (IFN-g), Tumor Necrosis Factor - alpha (TNF-a), Interleukin - 6 (IL-6), Matrix Metalloproteinase - 2 (MMP-2)
preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.
Change in levels of serum biomarkers HIF-1a & VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups.
Time Frame: after removal of tumor intraoperative (Ti) and 24 hours after surgery (T24h)
Change in levels of serum biomarkers HIF-1a & VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups
after removal of tumor intraoperative (Ti) and 24 hours after surgery (T24h)
Measure expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, γδT cells, NK cells and B cells peripheral blood lymphocytes at four time points
Time Frame: preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.
Measure expression of various lymphocyte
preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Centre

Investigators

  • Study Chair: Shubhada Chiplunkar, Tata Memorial Centre
  • Study Chair: Rajan Badwe, Tata Memorial Centre
  • Study Chair: Anuja Bidkar, Tata Memorial Centre
  • Study Chair: Reshma Ambulkar, Tata Memorial Centre
  • Study Chair: Raghu Thota, Tata Memorial Centre
  • Study Chair: Vani Parmar, Tata Memorial Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2017

Primary Completion (Estimated)

October 1, 2020

Study Completion (Estimated)

December 1, 2020

Study Registration Dates

First Submitted

December 20, 2016

First Submitted That Met QC Criteria

December 26, 2016

First Posted (Estimated)

December 29, 2016

Study Record Updates

Last Update Posted (Estimated)

December 21, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PN 219

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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