<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03005860</url>
  </required_header>
  <id_info>
    <org_study_id>PN 219</org_study_id>
    <nct_id>NCT03005860</nct_id>
  </id_info>
  <brief_title>Effect of TIVA Propofol vs Sevoflurane Anaesthetic on Serum Biomarkers and on PBMCs in Breast Cancer Surgery</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tata Memorial Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tata Memorial Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Surgery, perioperative stress, anaesthetics and analgesics may modulate the&#xD;
      immunosurveillance mechanisms and overwhelm host defences that normally maintain a balance&#xD;
      between immunity &amp; carcinogenesis. This may lead to escape of cancer cells and tilt the&#xD;
      scales toward a more protumorigenic microenvironment. Volatile agents, in particular, have&#xD;
      been shown to exhibit profound immunosuppressive effects. In comparison, propofol has a&#xD;
      favorable profile and inhibits cancer cell activity. Determining &quot;cancer-protective&quot; role of&#xD;
      TIVA with propofol presents an exciting window of opportunity that has potential to improve&#xD;
      outcomes in cancer patients undergoing resection surgery&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For the current study, consenting patients planned for upfront surgery, will be randomly&#xD;
      allocated to 2 groups- 20 patients each group: Propofol TCI-based Total Intravenous&#xD;
      Anesthesia group (Propofol group) and Sevoflurane group (Sevoflurane group), according to&#xD;
      computer generated randomization number.&#xD;
&#xD;
      Patients will be monitored routinely with ECG, non invasive blood pressure, and a pulse-&#xD;
      oximetery (SPO2), every 5 min. An intravenous access will be established with 20- 22 G&#xD;
      cannula. A perioperative antibiotic prophylaxis will be given to all patients. None of the&#xD;
      patients will receive any premedication.&#xD;
&#xD;
      After preoxygenation with 100% O2 for 3 min: group specific separate interventions will be&#xD;
      performed.&#xD;
&#xD;
      Patient will be ventilated with TV of 6-8ml/kg,respiratory rate will be adjusted to maintain&#xD;
      end-tidal CO2 value between 40 - 45 mmHg. Crystalloids will be used for hydration (4-6&#xD;
      ml/kg/h), and intraoperative volume deficits will be replaced by additional administration of&#xD;
      a solution according to clinical needs. For TIVA group, the depth of anaesthesia will be&#xD;
      monitored using Bispectral Index, with target BIS value between 40 and 60. For Sevoflurane&#xD;
      group, the depth of anaesthesia will be monitored using MAC, with target MAC value between&#xD;
      0.8 and 1. Half hour before conclusion of surgery, all patients will receive 0.1mg/kg of&#xD;
      ondansetron as prophylaxis for PONV. At the end of surgery, muscle relaxation will be&#xD;
      reversed by glycopyrrolate (10mcg/kg) and neostigmine (50mcg/kg).&#xD;
&#xD;
      Patients in both groups will receive intra-venous non-steroidal anti-inflammatory drug&#xD;
      1-1.5mg/kg diclofenac + Paracetamol 1gm just before conclusion of surgery for postoperative&#xD;
      analgesia. Postoperative pain &amp; PONV will be managed as per institutional protocols.&#xD;
&#xD;
      ASSAY Peripheral blood (5ml) will be collected from patients in EDTA vaccutainer and (5ml) in&#xD;
      another vaccutainer containing clot activator. The sample will be collected at following time&#xD;
      points.&#xD;
&#xD;
        1. before anaesthesia (Tpre)&#xD;
&#xD;
        2. after removal of tumor intraoperative (Ti)&#xD;
&#xD;
        3. 2 h after surgery (T2h) , and&#xD;
&#xD;
        4. (T24h) 24 hours after surgery&#xD;
&#xD;
      Estimation of serum cytokines : by sandwich ELISA and by cytokine bead array (CBA) method.&#xD;
&#xD;
      Expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T&#xD;
      cells, γδT cells, NK cells and B cells) by flow cytometry&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>February 2017</start_date>
  <completion_date type="Anticipated">February 2018</completion_date>
  <primary_completion_date type="Anticipated">January 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in baseline levels versus 24 hour postoperative levels (Tpre vs T24h ) of serum HIF-1a and VEGF-C in both groups.</measure>
    <time_frame>Baseline levels versus 24 hour postoperative levels (Tpre vs T24h )</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in levels of serum biomarkers HIF-1a &amp; VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups.</measure>
    <time_frame>after removal of tumor intraoperative (Ti) and 24 hours after surgery (T24h)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Female Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Fluoromethyl hexafluoroisopropyl ether</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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 &amp; 1.0.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2,6 diisopropylphenol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>2,6-Diisopropylphenol</intervention_name>
    <description>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.</description>
    <arm_group_label>2,6 diisopropylphenol</arm_group_label>
    <other_name>Fresofol 1%, Fresenius Kabi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluoromethyl hexafluoroisopropyl ether</intervention_name>
    <description>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.</description>
    <arm_group_label>Fluoromethyl hexafluoroisopropyl ether</arm_group_label>
    <other_name>Sevoflurane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl Citrate</intervention_name>
    <description>Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.</description>
    <arm_group_label>2,6 diisopropylphenol</arm_group_label>
    <arm_group_label>Fluoromethyl hexafluoroisopropyl ether</arm_group_label>
    <other_name>Verfen 100mcg/2ml, Verve</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atracurium Besylate</intervention_name>
    <description>Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement</description>
    <arm_group_label>2,6 diisopropylphenol</arm_group_label>
    <arm_group_label>Fluoromethyl hexafluoroisopropyl ether</arm_group_label>
    <other_name>Atrapure 25mg/2.5ml, Samarth Life Sciences Pvt. Ltd.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women with histopathologically (biopsy/FNAC) proven breast carcinoma with Resectable&#xD;
             disease (T 1-4, N 0-1, M 0) [Stage I-III].&#xD;
&#xD;
          2. Willing for upfront modified radical mastectomy.&#xD;
&#xD;
          3. ASA Physical Status 1-2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. use of morphine or on steroid therapy upto 3 months before surgery;&#xD;
&#xD;
          2. history of substance abuse or cognitive dysfunction;&#xD;
&#xD;
          3. endocrine disorders- diabetes, hypothyroid;&#xD;
&#xD;
          4. history of HIV, Hep-B or Hep-C infections;&#xD;
&#xD;
          5. Contraindication to analgesics or anaesthetic drugs;&#xD;
&#xD;
          6. Pregnant &amp; lactating women&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shubhada Chiplunkar</last_name>
    <role>Study Chair</role>
    <affiliation>Tata Memorial Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rajan Badwe</last_name>
    <role>Study Chair</role>
    <affiliation>Tata Memorial Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anuja Bidkar</last_name>
    <role>Study Chair</role>
    <affiliation>Tata Memorial Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Reshma Ambulkar</last_name>
    <role>Study Chair</role>
    <affiliation>Tata Memorial Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Raghu Thota</last_name>
    <role>Study Chair</role>
    <affiliation>Tata Memorial Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vani Parmar</last_name>
    <role>Study Chair</role>
    <affiliation>Tata Memorial Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jigeeshu Divatia, MD Anes.</last_name>
    <phone>2224146937</phone>
    <email>jdivatia@yahoo.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Tata Memorial Centre</name>
      <address>
        <city>Mumbai</city>
        <state>Maharashtra</state>
        <zip>400012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <results_reference>
    <citation>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.</citation>
    <PMID>22521561</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>16056258</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>15308095</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>21935924</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>12773983</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>20677220</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>17002789</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>24803747</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>23242747</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>14570648</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>12127688</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>20930611</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>24966150</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>26556730</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>17695450</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>December 26, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>January 12, 2017</last_update_submitted>
  <last_update_submitted_qc>January 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 16, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tata Memorial Centre</investigator_affiliation>
    <investigator_full_name>Dr. J. V. Divatia</investigator_full_name>
    <investigator_title>Professor and Head, Department Of Anaesthesia, Critical Care and Pain</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Propofol</mesh_term>
    <mesh_term>Sevoflurane</mesh_term>
    <mesh_term>Atracurium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03005860
org study id: PN 219
nct id: NCT03005860
lead sponsor: 
has dmc: Yes
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
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: 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 )
description: 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.
measure: 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)
measure: 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.
description: 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)
measure: 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.
arm group label: Fluoromethyl hexafluoroisopropyl ether
arm group type: Active Comparator
description: 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.
arm group label: 2,6 diisopropylphenol
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: 2,6-Diisopropylphenol
description: 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.
arm group label: 2,6 diisopropylphenol
other name: Fresofol 1%, Fresenius Kabi
intervention type: Drug
intervention name: Fluoromethyl hexafluoroisopropyl ether
description: 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.
arm group label: Fluoromethyl hexafluoroisopropyl ether
other name: Sevoflurane
intervention type: Drug
intervention name: Fentanyl Citrate
description: Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.
arm group label: 2,6 diisopropylphenol
arm group label: Fluoromethyl hexafluoroisopropyl ether
other name: Verfen 100mcg/2ml, Verve
intervention type: Drug
intervention name: Atracurium Besylate
description: Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement
arm group label: 2,6 diisopropylphenol
arm group label: Fluoromethyl hexafluoroisopropyl ether
other name: Atrapure 25mg/2.5ml, Samarth Life Sciences Pvt. Ltd.
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shubhada Chiplunkar
role: Study Chair
affiliation: Tata Memorial Centre
last name: Rajan Badwe
role: Study Chair
affiliation: Tata Memorial Centre
last name: Anuja Bidkar
role: Study Chair
affiliation: Tata Memorial Centre
last name: Reshma Ambulkar
role: Study Chair
affiliation: Tata Memorial Centre
last name: Raghu Thota
role: Study Chair
affiliation: Tata Memorial Centre
last name: Vani Parmar
role: Study Chair
affiliation: Tata Memorial Centre
last name: Jigeeshu Divatia, MD Anes.
phone: 2224146937
email: jdivatia@yahoo.com
facility: 
country: India
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PMID: 12773983
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PMID: 20677220
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PMID: 17002789
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PMID: 24803747
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PMID: 23242747
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PMID: 14570648
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PMID: 12127688
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PMID: 20930611
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PMID: 24966150
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PMID: 26556730
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PMID: 17695450
responsible party type: Principal Investigator
investigator affiliation: Tata Memorial Centre
investigator full name: Dr. J. V. Divatia
investigator title: Professor and Head, Department Of Anaesthesia, Critical Care and Pain
mesh term: Breast Neoplasms
mesh term: Fentanyl
mesh term: Propofol
mesh term: Sevoflurane
mesh term: Atracurium
sharing ipd: No