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CTRI Number  CTRI/2017/08/009548 [Registered on: 30/08/2017] Trial Registered Prospectively
Last Modified On: 14/12/2018
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   How does a sleeping medicine influence the blood particles during knee surgery  
Scientific Title of Study   To study the effect of dexmedetomidine on Ischemia-reperfusion injury after tourniquet release in patients undergoing total knee arthroplasty 
Trial Acronym  None  
Secondary IDs if Any  
Secondary ID  Identifier 
Nil  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Vanita Ahuja 
Designation  Associate Professor  
Affiliation  Department of Anaesthesia and Intensive care 
Address  GMCH Sector 32 Chandigarh
GMCH Sector 32
Chandigarh
CHANDIGARH
160030
India 
Phone  09646121649  
Fax    
Email  vanitaanupam@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Vanita Ahuja 
Designation  Associate Professor  
Affiliation  Department of Anaesthesia and Intensive care 
Address  GMCH Sector 32 Chandigarh
GMCH Sector 32
Chandigarh
CHANDIGARH
160030
India 
Phone  09646121649  
Fax    
Email  vanitaanupam@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Vanita Ahuja 
Designation  Associate Professor  
Affiliation  Department of Anaesthesia and Intensive care 
Address  GMCH Sector 32 Chandigarh
GMCH Sector 32
Chandigarh
CHANDIGARH
160030
India 
Phone  09646121649  
Fax    
Email  vanitaanupam@gmail.com  
 
Source of Monetary or Material Support  
Department of Anaesthesia and Intensive care GMCH Sector 32 Chandigarh  
 
Primary Sponsor  
Name  Department of Anaesthesia and Intensive care 
Address  GMCH Sector 32 Chandigarh 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Vanita Ahuja  Department of Anaesthesia and Intensive Care   Government Medical College and Hospital Sector 32 Chandigarh
Chandigarh
CHANDIGARH 
09646121649

vanitaanupam@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee (GMCH Chandigarh)   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: O||Medical and Surgical, Undergoing knee replacement surgery ,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  GA with propofol   GA with propofol and saline infusion  
Comparator Agent  GA with sevoflurane   GA with sevoflurane and saline infusion  
Intervention  Intravenous dexmedetomidine bolus and GA with propofol  GA with propofol and dexmedetomidine infusion  
Comparator Agent  Intravenous dexmedetomidine bolus and GA with sevoflurane   GA with sevoflurane and dexmedtomidine infusion  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Both 
Details  American Society of Anaesthesiologists physical status I and II
 
 
ExclusionCriteria 
Details  Patients with significant cardiorespiratory, hepatic, renal, haematological and neurological dysfunction

Patients on beta blockers, anticonvulsants, or any other centrally acting medications

Anticipated difficult airway

Pregnancy and lactation

Patient allergic to the study drug

Alcohol or substance abuse
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
malondialdehyde levels   baseline
1 minute pior to tourniquet deflation
5 minute and 30 minutes after tourniquet deflation 
 
Secondary Outcome  
Outcome  TimePoints 
Total anti oxidant status
Arterial blood gas analysis
Total tramadol consumption
Sevoflurane consumption
Haemodynamics  
baseline
1 minute pior to tourniquet deflation
5 minute and 30 minutes after tourniquet deflation  
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Post Marketing Surveillance 
Date of First Enrollment (India)   01/12/2017 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="6"
Days="15" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   Not yet  
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   Role of tourniquet application in lower limb surgery has dual benefits. It not only provides a bloodless filed to the surgeon but is an essential component of patient blood management strategies.1 During limb surgery, re-establishment of blood flow tourniquet deflation causes transient increase in end-tidal carbon dioxide and decrease in mean arterial blood pressure, temperature, and central venous oxygen tension. This also induces a paradoxical extension of ischaemic damages mediated by oxygen free radicals, known as the Ischaemia-reperfusion injury (IRI).2   IRI causes the release of free oxygen radicals initiate the production of malondialdehyde (MDA), through the lipid peroxidation of cellular membranes. Following lipid peroxidation, the antioxidant enzyme system is activated against reactive oxygen species (ROS) and attempts to protect cells from oxidative damage. There is a balance between the scavenging capacity of antioxidant 

enzymes and ROS.3 Because of this balance, the total antioxidant capacity (TAC) measurement is a sensitive indicator of the overall protective effects of the antioxidants.5-7

Currently, the preventive role of ischaemic preconditioning (IPC) is being considered in patients scheduled for total knee arthroplasties (TKA). The authors evaluated twenty patients scheduled for TKA and randomized them as IPC versus placebo. The muscle biopsies of patients in IPC group demonstrated a protective genomic response and increased oxidative stress defense mechanism as compared to placebo.8 However, IPC may not be possible in all the extremity surgeries.

Literature describes, effective role of  a 2 receptor agonist in prevention of release of catecholamine but is inconclusive with regard to IRI effects. In an adult study, brachial plexus anesthesia via axillary approach was performed for upper-limb surgeries. In the dexmedetomidine group, a continuous infusion of dexmedetomidine (1 microg/kg for 10 minutes, followed by 0.5 mg kg-1 h-1  was used until the end of surgery, whereas the control group received an equivalent volume of saline. Venous blood samples were obtained before brachial plexus anesthesia, at 1 minute before tourniquet release, and 15 minutes after tourniquet release for biochemical analysis. Dexmedetomidine significantly attenuated plasma hypoxanthine production in the ischemia and plasma MDA production in the reperfusion periods. Blood creatine phosphokinase and uric acid levels were significantly lower in the dexmedetomidine group compared with those in the control group after reperfusion.14 Recently, Bostankolu and coworkers reported the effects of dexmedetomidine on tourniquet-induced IRI in lower extremity surgeries performed under GA with sevoflurane in adult patients. Dexmedetomidine infusion versus normal saline was infused at a rate of 0.1μg/kg/minute (-1) for 10 minutes prior to induction and then at 0.7μg/kg/hour(-1) until 10 minutes before the end of the operation. Baseline blood samples, at 1 minute before tourniquet release and at 5 and 20 minutes after tourniquet release (ATR) reported decreased MDA levels when compared with the basal values and returned to baseline values at 20 minutes after tourniquet release. Dexmedetomidine did not have an additional protective role during routine general anesthesia.15.

The present study will be a prospective, randomized, placebo controlled trial.

   Sample size calculation: In  a previous study investigating the tourniquet-induced IRI in lower-extremity operations and assuming that the use of dexmedetomidine would result in 20% reduction in plasma MDA, the present study will require a sample size of 20 patients per group to achieve a power of 80% and α error of 0.05.10 To compensate for possible dropouts, we will enroll 25 patients per group

After approval of the protocol by Institutional Ethics Committee and written informed consent, 100 patients of either sex scheduled to undergo elective TKA under epidural analgesia + GA will be enrolled.

Arterial line insertion and blood samples

Following induction of GA, an anaesthesiologist under strict asepsis will perform arterial line insertion with 20 G arterial cannula. A base line arterial sample of 1 ml will be taken for arterial blood gases (ABG) including lactate and serum sample of 3 ml for MDA. Repeat samples will be taken at 1 minute before tourniquet deflation, 5 minutes and 30 minutes following tourniquet deflation.

Group allocation of the patients

Using computer generated random number table, patients will then be randomly allocated to one of the following four groups. Allocation concealment will be done using coded sealed opaque envelopes and decoding will be done at the end of the study.

Group I: (n = 25) GA maintenance with propofol 3-5 mg kg-1  hr-1  to maintain an entropy value of 40-60 + IV dexmedetomidine 0.5 μg kg-1  bolus in 10 ml normal saline (NS) over 10 minutes, followed by infusion at the rate 0.5μg kg-1  hr-1 ( @10 ml hr-1 ) .

Group II: (n =25) GA maintenance with propofol 3-5 mg kg-1 hr-1 to maintain an entropy value of 40-60 + IV 10 ml NS bolus over 10 minutes, followed by infusion of NS  @10 ml hr-1.

Group III: (n =25) GA maintenance with sevoflurane 0.4-2% to maintain an entropy value of 40-60 + IV dexmedetomidine 0.5μg kg-1 bolus in 10 ml NS over 10 minutes, followed by infusion at the rate 0.5μg kg-1  hr-1 ( @ 10 ml hr-1 ).

Group IV: (n =25) GA maintenance with sevoflurane 0.4-2% to maintain an entropy value of 40-60 + IV 10 ml NS bolus over 10 minutes, followed by infusion of NS  @10 ml hr-1.

 

 
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