Opioid Analgesic Adverse ReactionNCT04553536
Cardiovascular Protection Conservative Effects of Esketamine Versus µ-opioid Receptor Agonists in General Anesthesia
A study testing Esketamine, Sulfentanil or/and Remifentanil in people with Opioid Analgesic Adverse Reaction, run by Second Hospital of Shanxi Medical University at 1 site in China.
Trial summary
Pain is 'a double-edged sword', disturbing daily life of the sufferers and activating the intrinsic protective mechanisms. Transient receptor potential vanilloid 1 (TRPV1), play such role as 'a double agent', transmitting the pain signals and initiating the cardio-protective mechanism via release protective… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Opioid Analgesic Adverse Reaction
- What is being tested?
- Esketamine, Sulfentanil or/and Remifentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 1 siteChina
- Study dates
- 2 Nov 2020to 31 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients undergoing general anesthesia
Who cannot join
- Patients with diabetes and neuropathy
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zheng Guo
Taiyuan, Shanxi, 030001
Zheng Guo, MB，PhD, +863513365790, guozheng713@yahoo.com
Weijun Liang, MSc, +863513365790, weijun_liang@126.com
About this study
Official title: 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
Pain is 'a double-edged sword', disturbing daily life of the sufferers and activating the intrinsic protective mechanisms. Transient receptor potential vanilloid 1 (TRPV1), play such role as 'a double agent', transmitting the pain signals and initiating the cardio-protective mechanism via release protective neuropeptides.
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. We design this study to investigate the potential adverse effect of anesthesia with opioid as the main analgesic.
Read the detailed description
We hypothesize that over-analgesia using opioids significantly suppresses the activity of TRPV1/CGRP and SP 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.
- Conditions
- Opioid Analgesic Adverse Reaction
- Being tested
- Esketamine, Sulfentanil or/and Remifentanil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esketamine, Sulfentanil or/and RemifentanilDrug
Also called Propofol, Atracurium Besilate or Cisatracurium besylate or Rocuronium Bromide
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.
| Study group | Role | What they receive |
|---|---|---|
| Opioid analgesics | Active comparator | Mu-opioid receptor agonists (remifentanil, sulfentanil) will be used as the only analgesic(s) in the surgery. Receives: Drug: Esketamine, Sulfentanil or/and Remifentanil |
| Ketamine | Experimental | Esketamine will be used as the only anagesic in the surgey. Receives: Drug: Esketamine, Sulfentanil or/and Remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perioperative adverse cardiac events
It includes intra- and post-operative adverse cardiac events.
Measured: 72 hours
Cardiac protection related molecules, including transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP) and substance P.
The molecules exist in myocardium participating in carioprotection.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2020
- Study start2 Nov 2020
- Primary completion30 Jun 2023
- Study completion31 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Analgesic Adverse ReactionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Hospital of Shanxi Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zheng Guo, Second Hospital of Shanxi Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04553536
- Sponsor's protocol ID
- ZGuo20200826
- Status last verified
- Jan 2024
- First submitted
- 3 Sep 2020
- Last updated
- 25 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04553536
- Acronym / sponsor ID
- ZGuo20200826
- Conditions
- Opioid Analgesic Adverse Reaction
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Second Hospital of Shanxi Medical UniversityUniversity, hospital or other
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 31 Jan 2024 (estimated)
- First posted
- 17 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pain is 'a double-edged sword', disturbing daily life of the sufferers and activating the intrinsic protective mechanisms. Transient receptor potential vanilloid 1 (TRPV1), play such role as 'a double agent', transmitting the pain signals and initiating the cardio-protective mechanism via release protective neuropeptides.
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. We design this study to investigate the potential adverse effect of anesthesia with opioid as the main analgesic.
Detailed description
We hypothesize that over-analgesia using opioids significantly suppresses the activity of TRPV1/CGRP and SP 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Opioid analgesics | Active comparator | Drug: Esketamine, Sulfentanil or/and RemifentanilMu-opioid receptor agonists (remifentanil, sulfentanil) will be used as the only analgesic(s) in the surgery. |
| Ketamine | Experimental | Drug: Esketamine, Sulfentanil or/and RemifentanilEsketamine will be used as the only anagesic in the surgey. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Patients undergoing general anesthesia
Key exclusion criteria (1 listed)
- Patients with diabetes and neuropathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esketamine, Sulfentanil or/and RemifentanilAlso: Propofol, Atracurium Besilate or Cisatracurium besylate or Rocuronium BromideThe 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. | Drug | Ketamine, Opioid analgesics |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Esketamine, Sulfentanil or/and Remifentanil in people with Opioid Analgesic Adverse Reaction, run by Second Hospital of Shanxi Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perioperative adverse cardiac events (time frame: 72 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2024.