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

NCT ID: NCT03005860

Last Updated: 2023-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-01

Study Completion Date

2020-12-31

Brief Summary

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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

Detailed Description

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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

Conditions

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Female Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Fluoromethyl hexafluoroisopropyl ether

Intervention Type DRUG

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.

Fentanyl Citrate

Intervention Type DRUG

Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.

Atracurium Besylate

Intervention Type DRUG

Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement

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.

Group Type EXPERIMENTAL

2,6-Diisopropylphenol

Intervention Type DRUG

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.

Fentanyl Citrate

Intervention Type DRUG

Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.

Atracurium Besylate

Intervention Type DRUG

Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Fentanyl Citrate

Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.

Intervention Type DRUG

Atracurium Besylate

Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement

Intervention Type DRUG

Other Intervention Names

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Fresofol 1%, Fresenius Kabi Sevoflurane Verfen 100mcg/2ml, Verve Atrapure 25mg/2.5ml, Samarth Life Sciences Pvt. Ltd.

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Tata Memorial Centre

OTHER

Sponsor Role lead

Responsible Party

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Dr. J. V. Divatia

Professor and Head, Department Of Anaesthesia, Critical Care and Pain

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shubhada Chiplunkar

Role: STUDY_CHAIR

Tata Memorial Centre

Rajan Badwe

Role: STUDY_CHAIR

Tata Memorial Centre

Anuja Bidkar

Role: STUDY_CHAIR

Tata Memorial Centre

Reshma Ambulkar

Role: STUDY_CHAIR

Tata Memorial Centre

Raghu Thota

Role: STUDY_CHAIR

Tata Memorial Centre

Vani Parmar

Role: STUDY_CHAIR

Tata Memorial Centre

Locations

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Tata Memorial Centre

Mumbai, Maharashtra, India

Site Status

Countries

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India

References

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Dikshit RP, Yeole BB, Nagrani R, Dhillon P, Badwe R, Bray F. Increase in breast cancer incidence among older women in Mumbai: 30-year trends and predictions to 2025. Cancer Epidemiol. 2012 Aug;36(4):e215-20. doi: 10.1016/j.canep.2012.03.009. Epub 2012 Apr 20.

Reference Type RESULT
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Weigelt B, Peterse JL, van 't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005 Aug;5(8):591-602. doi: 10.1038/nrc1670.

Reference Type RESULT
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Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004 Aug;21(2):137-48. doi: 10.1016/j.immuni.2004.07.017.

Reference Type RESULT
PMID: 15308095 (View on PubMed)

Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012 Mar 15;130(6):1237-50. doi: 10.1002/ijc.26448. Epub 2011 Nov 9.

Reference Type RESULT
PMID: 21935924 (View on PubMed)

Tsuchiya Y, Sawada S, Yoshioka I, Ohashi Y, Matsuo M, Harimaya Y, Tsukada K, Saiki I. Increased surgical stress promotes tumor metastasis. Surgery. 2003 May;133(5):547-55. doi: 10.1067/msy.2003.141.

Reference Type RESULT
PMID: 12773983 (View on PubMed)

Boomsma MF, Garssen B, Slot E, Berbee M, Berkhof J, Meezenbroek Ede J, Slieker W, Visser A, Meijer S, Beelen RH. Breast cancer surgery-induced immunomodulation. J Surg Oncol. 2010 Nov 1;102(6):640-8. doi: 10.1002/jso.21662.

Reference Type RESULT
PMID: 20677220 (View on PubMed)

Camara O, Kavallaris A, Noschel H, Rengsberger M, Jorke C, Pachmann K. Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells. World J Surg Oncol. 2006 Sep 26;4:67. doi: 10.1186/1477-7819-4-67.

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Divatia JV, Ambulkar R. Anesthesia and cancer recurrence: What is the evidence? J Anaesthesiol Clin Pharmacol. 2014 Apr;30(2):147-50. doi: 10.4103/0970-9185.129990. No abstract available.

Reference Type RESULT
PMID: 24803747 (View on PubMed)

Heaney A, Buggy DJ. Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis? Br J Anaesth. 2012 Dec;109 Suppl 1:i17-i28. doi: 10.1093/bja/aes421.

Reference Type RESULT
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Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003 Nov;97(5):1331-1339. doi: 10.1213/01.ANE.0000082995.44040.07.

Reference Type RESULT
PMID: 14570648 (View on PubMed)

Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y, Nakamura H. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett. 2002 Oct 28;184(2):165-70. doi: 10.1016/s0304-3835(02)00210-0.

Reference Type RESULT
PMID: 12127688 (View on PubMed)

Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor beta in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010 Nov;113(5):1118-25. doi: 10.1097/ALN.0b013e3181f79a69.

Reference Type RESULT
PMID: 20930611 (View on PubMed)

Xu YJ, Chen WK, Zhu Y, Wang SL, Miao CH. Effect of thoracic epidural anaesthesia on serum vascular endothelial growth factor C and cytokines in patients undergoing anaesthesia and surgery for colon cancer. Br J Anaesth. 2014 Jul;113 Suppl 1:i49-55. doi: 10.1093/bja/aeu148. Epub 2014 Jun 25.

Reference Type RESULT
PMID: 24966150 (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 RESULT
PMID: 26556730 (View on PubMed)

Gisterek I, Matkowski R, Kozlak J, Dus D, Lacko A, Szelachowska J, Kornafel J. Evaluation of prognostic value of VEGF-C and VEGF-D in breast cancer--10 years follow-up analysis. Anticancer Res. 2007 Jul-Aug;27(4C):2797-802.

Reference Type RESULT
PMID: 17695450 (View on PubMed)

Other Identifiers

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PN 219

Identifier Type: -

Identifier Source: org_study_id