Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cardiovascular Protection Conservative Effects of Esketamine Versus µ-opioid Receptor Agonists in General Anesthesia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04553536
Recruitment Status : Recruiting
First Posted : September 17, 2020
Last Update Posted : March 17, 2021
Sponsor:
Information provided by (Responsible Party):
Zheng Guo, Second Hospital of Shanxi Medical University

Tracking Information
First Submitted Date  ICMJE September 3, 2020
First Posted Date  ICMJE September 17, 2020
Last Update Posted Date March 17, 2021
Actual Study Start Date  ICMJE November 2, 2020
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2020)
  • Perioperative adverse cardiac events [ Time Frame: 72 hours ]
    It includes intra- and post-operative adverse cardiac events.
  • Cardiac protection related molecules, including transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP) and substance P. [ Time Frame: 24 hours ]
    The molecules exist in myocardium participating in carioprotection.
Original Primary Outcome Measures  ICMJE
 (submitted: September 11, 2020)
  • Perioperative adverse cardiac events [ Time Frame: 72 hours ]
    It includes intra- and post-operative adverse cardiac events.
  • Cardiac protection related molecules, including transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP) and substance P. [ Time Frame: 24h ]
    The molecules exist in myocardium participating in carioprotection.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiovascular Protection Conservative Effects of Esketamine Versus µ-opioid Receptor Agonists in General Anesthesia
Official Title  ICMJE Perioperative Cardiovascular Protection Conservative Effects of Esketamine Versus µ-opioid Receptor Agonists in Total Intravenous General Anesthesia: Study Protocol for a Randomized Controlled Pilot Trial
Brief Summary

Pain has two sides. The 'bad pain' refers to the adverse impact of pain on humans, which disturbs daily life of the sufferers. Evidence indicates that in the transduction and transmission of the painful signals some molecules may retrogradely moving to the tissues where the pain was initiated, to provide protection to the cells and the organ being insulted by the nociceptive stimulation. Transient receptor potential vanilloid 1 (TRPV1), as a nociceptor, promotes the release of calcitonin gene-related peptide (CGRP) and substance P (SP) in the small diameter primary sensory neurons, mediating the pain signals from nociceptor to the spinal dorsal horn, sending the pain signals to the central nervous system. In the same time, the neuropeptides are released from the peripheral nerve terminals of the innervating neurons, where the harmful stimulation occurred, including the heart and vasculature. CGRP and SP play important roles in cardio-protection and homeostasis of systemic hemodynamics via the neurogenic mechanism. All the beneficial effects initiated by pain is mentioned as 'good pain' by physiologists.

Surgery-related pain is mostly so severe and disturbing that must be medically treated. Unfortunately, the beneficial aspect of pain is commonly ignored in daily clinical practice. Does it matter to the patients' outcomes? We don't know yet! What we have been seeing is the shocking outcomes of patients underwent surgery, which shows about 0.8% and 7% of mortalities in the period of 48 hours and 30 days after surgery, respectively (https://www.rcplondon.ac.uk/projects/outputs/national-hip-fracture-database-annual-report-2016; Injury. 2017; 48(10): 2180-2183). What causes the disaster? Piles of evidence demonstrate that deep anesthesia or deep sedation is related to the high mortality of the patients (Anesthesiology. 2012; 116:1195-1203; Crit Care. 2014; 18(4):R156 ). What about the effect of analgesia, especially the over-analgesia, on the patients' outcome in and after surgery? Opioids are the most commonly used drugs in the treatment of moderate and sever pain including intra- and postoperative pain. The µ-opioid receptor agonists induce analgesic effect via inhibition of the transduction and the transmission of pain signals, by suppression of the release of CGRP and SP from the nerve terminals. The protective effects on cardiovascular system mediated by CGRP and SP can be inhibited, if the same effect is produced by the action of opioids in the peripheral nerve terminals innervating the heart and the vasculature. Our previous research shows that intrathecal administration of morphine or epidural administration of ropivacaine (1%, in 20 μL) significantly attenuates the increases of CGRP and its coding mRNA in ventricular myocardium and the innervating dorsal root ganglion neurons following occlusion of coronary artery in experimental animals. Based on the evidence, we hypothesize that over-analgesia using opioids significantly suppresses the activity of TRPV1/CGRP、SP mechanism and reduces the amount of CGRP and SP released, which results in an effective de-protection of the cardiovascular system. The severer myocardial damage under some insulting circumstances and eventful systemic hemodynamics is likely occurring upon some surgical/pathological/pharmacological insults in the intra- and postoperative periods.

This parallel, randomized controlled trial will be conducted in eleven centers in Shanxi province, China, which is designed to investigate the perioperative incidence of adverse cardiovascular events and alteration of cardiac troponin I (cTnI) in the patients (one thousand patients, ASA Physical Status 1-II, older than 16 years, regardless of the gender) undergoing surgery under total intravenous general anesthesia with conventional µ-opioid agonists or Esketamine, as the major analgesic. Clinically appropriate anesthesia depth or BIS readings will be used for judgement of anesthetic depth. Conventional monitoring parameters, including blood pressures, heart rate, SpO2 and ECG, will be recorded and analyzed. Blood samples will be collected at 30 min before induction of anesthesia, at the end of surgery and 24 h after the surgery. The association of the perioperative adverse cardiovascular events and the alterations of the levels of serum TRPV1, CGRP, SP and cTnI in the patients underwent general anesthesia using different analgesics (µ-opioid agonists vs Esketamine) will be evaluated. Postoperative outcome, including the functions of the brain and cardiovascular system, is also going to be traced for 1 year postoperatively.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
Condition  ICMJE Opioid Analgesic Adverse Reaction
Intervention  ICMJE Drug: Esketamine, Sulfentanil or/and Remifentanil
The esketamine or the opioids will be intravenously injected or infused to the patients with propofol and one of the muscle relaxants to induce and maitain general anesthesia.
Other Name: Propofol, Atracurium Besilate or Cisatracurium besylate or Rocuronium Bromide
Study Arms  ICMJE
  • Active Comparator: Opioid analgesics
    Mu-opioid receptor agonists (remifentanil, sulfentanil) will be used as the only analgesic(s) in the surgery.
    Intervention: Drug: Esketamine, Sulfentanil or/and Remifentanil
  • Experimental: Ketamine
    Esketamine will be used as the only anagesic in the surgey.
    Intervention: Drug: Esketamine, Sulfentanil or/and Remifentanil
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2020)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2022
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients undergoing general anesthesia

Exclusion Criteria:

  • Patients with diabetes and neuropathy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04553536
Other Study ID Numbers  ICMJE ZGuo20200826
Has Data Monitoring Committee Not Provided
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 Not Provided
Responsible Party Zheng Guo, Second Hospital of Shanxi Medical University
Study Sponsor  ICMJE Second Hospital of Shanxi Medical University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Second Hospital of Shanxi Medical University
Verification Date March 2021

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