Ignite Creation Date:
2024-05-06 @ 2:15 AM
Last Modification Date:
2024-10-26 @ 11:16 AM
Study NCT ID:
NCT02007798
Status:
UNKNOWN
Last Update Posted:
2014-01-14
First Post:
2013-12-06
Brief Title:
Small-dose Dexmedetomidine Effects on Recovery Profiles of Supratentorial Tumors Patients From General Anesthesia
Sponsor:
China Medical University China
Organization:
China Medical University China
Study Overview
Official Title:
Randomized Parallelled and Double-blinded Trial of Small-dose Dexmedetomidine Effects on Recovery Profiles of Supratentorial Tumors Patients From General Anesthesia
Status:
UNKNOWN
Status Verified Date:
2014-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
An excellent recovery profile is critical for neurosurgical anesthesia Rapid awakening smooth blood pressure and heart rate HR a higher degree of coordination painless or mild pain as well as better tolerance to endotracheal intubation can avoid can increased intracranial pressure elevated blood pressure and rapid HR caused by emergency choking suffocation and agitation and can reduce postoperative cerebral edema and the risk of bleeding In addition it is easy for surgeons to timely evaluate postoperative patients neurologic function based on the excellent recovery from anesthesia Up to now there are many methods and drugs to improve the quality of recovery period but each of them has some flaws Dexmedetomidine an emerging anesthetic adjuvant exhibits a stable hemodynamic recovery period and cannot affect evaluation of neurological function with both the sedative and analgesic effects We propose the following hypotheses 1 A small dose of dexmedetomidine can be intravenously injected into patients subjected to craniotomy under general anesthesia in order to improve the recovery profiles and reduce the incidence of emergence agitation 2 Dexmedetomidine can reduce postoperative pain
Detailed Description:
Study Arms
Enrollment There are totally 150 cases 50 cases in each group At least 120 cases complete the test
Randomized grouping Under the guidance of a drug administrator the different drug and control groups are randomly encoded Each code has a corresponding emergency envelope Blind codes are saved by the drug administrator
Interventions
Experimental Drugs Dexmedetomidine SFDA Approval No H20090248 200 ug2 ml provided by the Central Pharmacy of the First Affiliated Hospital of China Medical University and produced by Jiangsu Hengrui Medicine Co Ltd China
Normal saline 100 ml per bag provided by the the Central Pharmacy of the First Affiliated Hospital of China Medical University
Experimental Procedures
Background Information Dexmedetomidine is an α-adrenoceptor agonist and its chemical name is -4-S-1-23-dimethylphenyl ethyl-1H-imidazole hydrochloride Its structure and pharmacological activity are similar to clonidine Dexmedetomidine was developed by the Orion Pharma Finland Corporation and Abott USA and introduced to China in 2009 trade name Ai Beining Preclinical studies have shown that like clonidine dexmedetomidine is an agonist of α2-adrenergic receptors and exhibits effectiveness about 10 times more than clonidine Originally developed as an antihypertensive drug dexmedetomidine functions in lowering blood pressure and HR and is found to have a powerful anesthetic effect Up to now dexmedetomidine has been widely used in general anesthesia monitored anesthesia care MAC ICU sedation Dexmedetomidine is a sedative hypnotic analgesic anti-sympathetic medication and uniquely characterized as cooperative sedation and no respiratory depression
In the present study we compare the hemodynamic effects of different doses of dexmedetomidine via intraoperative infusion and explore the effects of dexmedetomidine on recovery profiles from general anesthesia and postoperative pain
Experimental Protocol
This study is a randomized double-blinded trial All the subjects are supratentorial brain tumors patients with ASA I II Within 24 hours before surgery preoperative visits are conducted to obtain signed informed consents The patients height weight blood pressure including SBP DBP and mean arterial pressure MAP HR oxygen saturation SpO2 are recorded as the baseline value BV
Patients are subjected to electrocardiograph monitoring including non-invasive blood pressure ECG and SpO2
Anesthesia is orderly induced by a combined infusion of propofol 2-25 mgkg sufentanil 03-05 ugkg and cis-atracurium 015-02 mgkg and the tracheal intubation is completed until the maximal muscle relaxant effect
Before surgery arterial and central venous catheterization is completed for continuous monitoring of the patients arterial pressure and central venous pressure CVP Intraoperative CVP is maintained at 4-6 cmH2O
Anesthesia is maintained at a manner of inhalation anesthesia with 08-15 sevoflurane and continuous intravenous infusion of propofol and remifentanil respectively at a speed of 3-5 mgkgh and 001-002 mg kgh The drug dose is adjusted hemodynamically to maintain MAP values at a range of 60-90 mmHg
After craniectomy additional cis-atracurium 005-008 mgkg is added every 45-60 minutes by the end of dural suturing Sufentanil 015-02 ugkg is given intravenously instead of inhalation anesthesia and meanwhile 20 -30 dose of intravenous anesthesia is added After skin closure approximately 30 minutes before the end of surgery continuous infusion of propofol is terminated and remifentanil infusion is stopped after surgery Intraoperative dexamethasone 20 mg is routinely used for prevention of cerebral edema 10 mg is administered intravenously before surgery 10 mg and then an additional 10 mg injected after 2 hours or by the end of surgery
Infusion principles before anesthesia crystalloid solution is dropped at a speed of 8-10 mlkgh After the start of anesthesia the infusion speed is adjusted to 5mlkgh The dose of artificial colloids is less than 20 mlkg The infusion volume is adjusted based on the amount of fluid input and output
Experimental drugs are infused via the syringe pump approximately 1 hour before the end of surgery ie at the end of dural suturing at a speed of 2 mlmin ie 120 mlh
Criteria for extubation a recovery of spontaneous breathing b over 95 SpO2 c patients can complete the instructions eye opening to voice
Criteria for discharge from the Post Anesthesia Care Unit PACU a 1 RASS score -2 b in the case of oxygen inhalation via a nasal catheter at a flow rate of 3-5 Lmin SpO2 can maintain above 95 c the observation time after extubation is 30 minutes
Medical equipments used in surgery GE healthcare SolarTM8000Mi Patient Monitor GE healthcare Smart Anesthesia Multi-gas SAMTMSAM-80 Module multi-gas analyzer Drager Fabius GS JMS syringe pump SP-500
Medical equipments used in PACU GE healthcare B30 Patient Monitor NHI ventilator Newport Medical Instruments Inc USA
Medical equipments used in Neurosurgical intensive care unit NICU GE Dash 2500 Monitor GEM Premier 3000 blood gas analyzer
Adverse Events
All the adverse events occur after drug administration which may be unrelated to drug treatment
Observation and recording of adverse effects Careful inquiry and tracing is necessary for all the adverse events during the experiment including laboratory abnormalities All adverse events must be judged by their nature severity and correlation with drug treatment which should be strictly recorded in the case report form
Correlation assessment Correlations between adverse events and experimental medication are as follows definitely related probably related possibly related possibly unrelated certainly unrelated The incidence of adverse reactions is calculated based on three conditions described as definitely related probably related and possibly related Specific criteria are seen in Appendix 1
Severity assessment
Severity of adverse events is divided into three levels
Mild Treatment is usually not necessary for a transient increase in blood pressure and decrease in HR because the subject is under anesthesia
Moderate The bolus injection of atropine 03-1 mg is given for sinus bradycardia and escape rhythm If combination with hypotension the bolus injection of ephedrine 10-15 mg can be applied
Severe For sinus standstill cardiopulmonary resuscitation is applied if necessary
Treatment for adverse events during and after the experiment Outcomes of all adverse events should be followed and recorded The subject who withdraws from the experiment due to adverse events should be traced till the adverse events completed removed Researchers must determine whether an adverse event is related to experimental drugs and provide a basis to support this judgment
Serious adverse events Definition Adverse events occur during clinical trials that result in a series of serious consequences including hospitalization prolonging hospitalization disability affecting the ability to work endangering the life or death and congenital malformations
Reporting of the serious adverse events Serious adverse reactions should be reported to the team leader and sponsor within 24 hours and the serious adverse event table should be filled
Contacts Yue Yun 86 13889168717 Second Department of Anesthesiology First Affiliated Hospital of China Medical University China Urgent Unblinding Method When serious adverse reactions appear during the experiment if necessary the study director can open the emergency envelope to carry out urgent unblinding strategy and record the relevant causes and date in the case report form Whether the unblinded subjects withdraw from the experiment is decided by investigators and responsible party
Data management and Statistical Analyses
Statistical Description Completed case report forms are collected by the clinical inspector and submitted to the responsible party for data processing
After confirmation the data from case report forms are locked into the database
There are 3 groups when unblinding for the first time Information description Count data are described using percentages and measurement data expressed as mean standard deviation Not normally distributed data are expressed as median and percentiles 25th-75th percentiles
Comparison of baseline data Intergroup count data are compared using chi-square test or Fishers exact test If measurement data normally distributed exhibit homogeneity of variance single-factor or multi-factor analysis of variance is applied If heterogeneity of variance is shown non-parametric test or approximate test eg Tamhnnes T2 test is employed For measurement data not normally distributed non-parametric Mann-Whitney U test or Kruskall-Wallis rank sum test is used Baseline balance and comparability in each group is examined
Comparison of Efficacy Analgesic and sedative effects between groups are compared using Kruskall-Wallis rank sum test For markedly effective pairwise comparison in data differences between are analyzed using Mann-Whitney U non-parametric test Considering the center or other factors CMH X2 test is employed for comparison of two-classification index and level indicators
Data Processing All statistical data are analyzed using SAS software for data processing Two-sided test is employed for statistical analysis and the corresponding P values are given For the Fishers exact test P value is calculated directly A value of P 005 is considered significant and P 001 considered highly significant
Unblinding for the second time is carried out by the end of statistical analysis and there are two experimental groups and one control group
Quality Assurance and Quality Control
Investigators In this clinical study there are two responsible parties and five principal investigators The clinical scheme is implemented strictly An inspector is appointed to monitor the clinical trial at any time
Quality Control of the measurement indexes The observation indexes are observed according to standard operating procedures and quality control procedures National legal units of measurements are employed for various test items The test report form must complete the Assay report card must have complete items including the date test items test results and their normal range
Ethical standards The study protocol case report forms informed consent should be approved by the Ethics Committee of the First Affiliated Hospital of China Medical University
Investigators or investigator-authorized officers will be responsible to explain the benefits and risks of participating in the clinical trial for each patient the patients legal representative or notary witnesses The written informed consent should be obtained prior to study entry before screening test and drug administration
All the patients or their legal representatives and personnel chairing the informed consent process sign their names and date to the informed consent The original file is saved by the investigators
Data retention The investigators should be responsible for the intact data intact have a fixed place to store the data which are locked for future viewing In accordance with the principles of GCP in China the data should be kept for at least 5 years
Enrollment There are totally 150 cases 50 cases in each group At least 120 cases complete the test
Randomized grouping Under the guidance of a drug administrator the different drug and control groups are randomly encoded Each code has a corresponding emergency envelope Blind codes are saved by the drug administrator
Interventions
Experimental Drugs Dexmedetomidine SFDA Approval No H20090248 200 ug2 ml provided by the Central Pharmacy of the First Affiliated Hospital of China Medical University and produced by Jiangsu Hengrui Medicine Co Ltd China
Normal saline 100 ml per bag provided by the the Central Pharmacy of the First Affiliated Hospital of China Medical University
Experimental Procedures
Background Information Dexmedetomidine is an α-adrenoceptor agonist and its chemical name is -4-S-1-23-dimethylphenyl ethyl-1H-imidazole hydrochloride Its structure and pharmacological activity are similar to clonidine Dexmedetomidine was developed by the Orion Pharma Finland Corporation and Abott USA and introduced to China in 2009 trade name Ai Beining Preclinical studies have shown that like clonidine dexmedetomidine is an agonist of α2-adrenergic receptors and exhibits effectiveness about 10 times more than clonidine Originally developed as an antihypertensive drug dexmedetomidine functions in lowering blood pressure and HR and is found to have a powerful anesthetic effect Up to now dexmedetomidine has been widely used in general anesthesia monitored anesthesia care MAC ICU sedation Dexmedetomidine is a sedative hypnotic analgesic anti-sympathetic medication and uniquely characterized as cooperative sedation and no respiratory depression
In the present study we compare the hemodynamic effects of different doses of dexmedetomidine via intraoperative infusion and explore the effects of dexmedetomidine on recovery profiles from general anesthesia and postoperative pain
Experimental Protocol
This study is a randomized double-blinded trial All the subjects are supratentorial brain tumors patients with ASA I II Within 24 hours before surgery preoperative visits are conducted to obtain signed informed consents The patients height weight blood pressure including SBP DBP and mean arterial pressure MAP HR oxygen saturation SpO2 are recorded as the baseline value BV
Patients are subjected to electrocardiograph monitoring including non-invasive blood pressure ECG and SpO2
Anesthesia is orderly induced by a combined infusion of propofol 2-25 mgkg sufentanil 03-05 ugkg and cis-atracurium 015-02 mgkg and the tracheal intubation is completed until the maximal muscle relaxant effect
Before surgery arterial and central venous catheterization is completed for continuous monitoring of the patients arterial pressure and central venous pressure CVP Intraoperative CVP is maintained at 4-6 cmH2O
Anesthesia is maintained at a manner of inhalation anesthesia with 08-15 sevoflurane and continuous intravenous infusion of propofol and remifentanil respectively at a speed of 3-5 mgkgh and 001-002 mg kgh The drug dose is adjusted hemodynamically to maintain MAP values at a range of 60-90 mmHg
After craniectomy additional cis-atracurium 005-008 mgkg is added every 45-60 minutes by the end of dural suturing Sufentanil 015-02 ugkg is given intravenously instead of inhalation anesthesia and meanwhile 20 -30 dose of intravenous anesthesia is added After skin closure approximately 30 minutes before the end of surgery continuous infusion of propofol is terminated and remifentanil infusion is stopped after surgery Intraoperative dexamethasone 20 mg is routinely used for prevention of cerebral edema 10 mg is administered intravenously before surgery 10 mg and then an additional 10 mg injected after 2 hours or by the end of surgery
Infusion principles before anesthesia crystalloid solution is dropped at a speed of 8-10 mlkgh After the start of anesthesia the infusion speed is adjusted to 5mlkgh The dose of artificial colloids is less than 20 mlkg The infusion volume is adjusted based on the amount of fluid input and output
Experimental drugs are infused via the syringe pump approximately 1 hour before the end of surgery ie at the end of dural suturing at a speed of 2 mlmin ie 120 mlh
Criteria for extubation a recovery of spontaneous breathing b over 95 SpO2 c patients can complete the instructions eye opening to voice
Criteria for discharge from the Post Anesthesia Care Unit PACU a 1 RASS score -2 b in the case of oxygen inhalation via a nasal catheter at a flow rate of 3-5 Lmin SpO2 can maintain above 95 c the observation time after extubation is 30 minutes
Medical equipments used in surgery GE healthcare SolarTM8000Mi Patient Monitor GE healthcare Smart Anesthesia Multi-gas SAMTMSAM-80 Module multi-gas analyzer Drager Fabius GS JMS syringe pump SP-500
Medical equipments used in PACU GE healthcare B30 Patient Monitor NHI ventilator Newport Medical Instruments Inc USA
Medical equipments used in Neurosurgical intensive care unit NICU GE Dash 2500 Monitor GEM Premier 3000 blood gas analyzer
Adverse Events
All the adverse events occur after drug administration which may be unrelated to drug treatment
Observation and recording of adverse effects Careful inquiry and tracing is necessary for all the adverse events during the experiment including laboratory abnormalities All adverse events must be judged by their nature severity and correlation with drug treatment which should be strictly recorded in the case report form
Correlation assessment Correlations between adverse events and experimental medication are as follows definitely related probably related possibly related possibly unrelated certainly unrelated The incidence of adverse reactions is calculated based on three conditions described as definitely related probably related and possibly related Specific criteria are seen in Appendix 1
Severity assessment
Severity of adverse events is divided into three levels
Mild Treatment is usually not necessary for a transient increase in blood pressure and decrease in HR because the subject is under anesthesia
Moderate The bolus injection of atropine 03-1 mg is given for sinus bradycardia and escape rhythm If combination with hypotension the bolus injection of ephedrine 10-15 mg can be applied
Severe For sinus standstill cardiopulmonary resuscitation is applied if necessary
Treatment for adverse events during and after the experiment Outcomes of all adverse events should be followed and recorded The subject who withdraws from the experiment due to adverse events should be traced till the adverse events completed removed Researchers must determine whether an adverse event is related to experimental drugs and provide a basis to support this judgment
Serious adverse events Definition Adverse events occur during clinical trials that result in a series of serious consequences including hospitalization prolonging hospitalization disability affecting the ability to work endangering the life or death and congenital malformations
Reporting of the serious adverse events Serious adverse reactions should be reported to the team leader and sponsor within 24 hours and the serious adverse event table should be filled
Contacts Yue Yun 86 13889168717 Second Department of Anesthesiology First Affiliated Hospital of China Medical University China Urgent Unblinding Method When serious adverse reactions appear during the experiment if necessary the study director can open the emergency envelope to carry out urgent unblinding strategy and record the relevant causes and date in the case report form Whether the unblinded subjects withdraw from the experiment is decided by investigators and responsible party
Data management and Statistical Analyses
Statistical Description Completed case report forms are collected by the clinical inspector and submitted to the responsible party for data processing
After confirmation the data from case report forms are locked into the database
There are 3 groups when unblinding for the first time Information description Count data are described using percentages and measurement data expressed as mean standard deviation Not normally distributed data are expressed as median and percentiles 25th-75th percentiles
Comparison of baseline data Intergroup count data are compared using chi-square test or Fishers exact test If measurement data normally distributed exhibit homogeneity of variance single-factor or multi-factor analysis of variance is applied If heterogeneity of variance is shown non-parametric test or approximate test eg Tamhnnes T2 test is employed For measurement data not normally distributed non-parametric Mann-Whitney U test or Kruskall-Wallis rank sum test is used Baseline balance and comparability in each group is examined
Comparison of Efficacy Analgesic and sedative effects between groups are compared using Kruskall-Wallis rank sum test For markedly effective pairwise comparison in data differences between are analyzed using Mann-Whitney U non-parametric test Considering the center or other factors CMH X2 test is employed for comparison of two-classification index and level indicators
Data Processing All statistical data are analyzed using SAS software for data processing Two-sided test is employed for statistical analysis and the corresponding P values are given For the Fishers exact test P value is calculated directly A value of P 005 is considered significant and P 001 considered highly significant
Unblinding for the second time is carried out by the end of statistical analysis and there are two experimental groups and one control group
Quality Assurance and Quality Control
Investigators In this clinical study there are two responsible parties and five principal investigators The clinical scheme is implemented strictly An inspector is appointed to monitor the clinical trial at any time
Quality Control of the measurement indexes The observation indexes are observed according to standard operating procedures and quality control procedures National legal units of measurements are employed for various test items The test report form must complete the Assay report card must have complete items including the date test items test results and their normal range
Ethical standards The study protocol case report forms informed consent should be approved by the Ethics Committee of the First Affiliated Hospital of China Medical University
Investigators or investigator-authorized officers will be responsible to explain the benefits and risks of participating in the clinical trial for each patient the patients legal representative or notary witnesses The written informed consent should be obtained prior to study entry before screening test and drug administration
All the patients or their legal representatives and personnel chairing the informed consent process sign their names and date to the informed consent The original file is saved by the investigators
Data retention The investigators should be responsible for the intact data intact have a fixed place to store the data which are locked for future viewing In accordance with the principles of GCP in China the data should be kept for at least 5 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None