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Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery.

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ClinicalTrials.gov Identifier: NCT03772054
Recruitment Status : Completed
First Posted : December 11, 2018
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
Felipe Andrés Maldonado Caniulao, University of Chile

Tracking Information
First Submitted Date  ICMJE December 9, 2018
First Posted Date  ICMJE December 11, 2018
Last Update Posted Date December 12, 2019
Actual Study Start Date  ICMJE December 20, 2018
Actual Primary Completion Date December 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2018)
Syndecan-1 levels [ Time Frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR ]
Differences in the concentration of syndecan-1 in blood serum during and after surgery
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2018)
  • Heparan sulfate levels [ Time Frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR ]
    Differences in the concentration of heparan sulfate in blood serum during and after surgery
  • Thrombomodulin [ Time Frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR ]
    Differences in the concentration of thrombomodulin in blood serum during and after surgery
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery.
Official Title  ICMJE Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery. A Randomized Controlled Trial
Brief Summary Endothelial damage has been reported after ischemia-reperfusion events. This can be characterized by measurements of glycocalyx and endothelial components that are released to blood after the insult. Sevoflurane and inhaled anesthetic commonly used for surgery have shown protective endothelial effects in animal and in-vitro models. Knee-ligament surgery with the use of a femoral tourniquet generates a transient ischemia-reperfusion (IR) state after the tourniquet is released. This research aims to compare the effect of sevoflurane and propofol in the release of glycocalyx and endothelial biomarkers after IR in this surgical scenario.
Detailed Description

To study the anesthetics effect on the endothelial damage induced by Ischemia-reperfusion (IR) in knee-ligament surgery, we will perform a randomized controlled clinical trial comparing the concentrations of syndecan-1 and heparan sulfate, both markers of superficial glycocalyx shedding and the concentration of thrombomodulin, a marker of endothelial cell damage, in serum of patients under hypnosis with sevoflurane or propofol after a spinal anesthesia.

After ethical review board approval and patients consent, 16 subjects (8 per group) scheduled for Knee-ligament replacement will be randomly allocated in one of the two parallel arms of the study. All patients will enter the operating room and after standard ASA monitorization and placement of an intravenous line (IV), a spinal anesthesia will be performed under midazolam sedation. After analgesia and motor block establishment, an intravenous or inhalation hypnosis induction will be performed (according to the study arm allocation). The airway will be secured by a laryngeal mask placement and the surgery will be started. A femoral tourniquet will be installed and inflated by surgeon indication at 100-120 mmHg over patient systolic blood pressure. Blood samples to measure endothelial damage biomarkers will be taken in five different moments to follow concentration changes before and after the IR insult. Fluid and drugs administration will be standardized.

Venous blood samples will be collected at the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR. After obtaining all samples, serum syndecan-1, heparan sulfate, and thrombomodulin will be measured by a researcher blinded to patient allocation using commercial available Elisa kits. The concentration of each biomarker at each sample time will be compared.

A sample size calculation was performed based on a few clinical reports to detect a 25% reduction in the mean concentration of syndecan-1 in the sevoflurane group with an alpha of 0,05 and a power of 80%. Then 16 patients (8 patients per arm) will be enrolled for a two-sides test analysis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
Blood samples will be codified by the principal investigator. Laboratory team will receive all samples for biomarkers measures. Results will be analyzed by the principal investigator.
Primary Purpose: Prevention
Condition  ICMJE Ischemia Reperfusion Injury
Intervention  ICMJE
  • Drug: Sevoflurane
    Inhalation anesthetic agent
  • Drug: Propofol
    Intravenous anesthetic agent
Study Arms  ICMJE
  • Active Comparator: Propofol
    After spinal anesthesia, patients in this arm will receive an intravenous target controlled infusion to site effect (TCI/Ce) infusion of propofol to achieve hypnosis guided to a bispectral index (BIS) level of 40-60 during surgery.
    Intervention: Drug: Propofol
  • Experimental: Sevoflurane
    After spinal anesthesia, patients in this arm will receive an inhalation induction with sevoflurane to achieve hypnosis guided to 0.7-0.9 minimum alveolar concentration (MAC) during surgery.
    Intervention: Drug: Sevoflurane
Publications * Maldonado F, Morales D, Gutiérrez R, Barahona M, Cerda O, Cáceres M. Effect of sevoflurane and propofol on tourniquet-induced endothelial damage: a pilot randomized controlled trial for knee-ligament surgery. BMC Anesthesiol. 2020 May 20;20(1):121. doi: 10.1186/s12871-020-01030-w.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 9, 2018)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 11, 2019
Actual Primary Completion Date December 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • American Society of Anesthesiologists Classification (ASA Class) I and II
  • Elective knee ligament surgery
  • Use of a femoral tourniquet

Exclusion Criteria:

  • Allergies to egg or soya
  • Previous history of critical events during surgery and perioperative period
  • Patients at risk of hyperthermia malignant
  • Patients with 3 or more predictor of difficult airway management
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03772054
Other Study ID Numbers  ICMJE 903/17
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Felipe Andrés Maldonado Caniulao, University of Chile
Study Sponsor  ICMJE University of Chile
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Felipe Maldonado, M.D., M.Sc. Hospital Clìnico de la Universidad de Chile.
PRS Account University of Chile
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP