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CTRI Number  CTRI/2020/12/030150 [Registered on: 31/12/2020] Trial Registered Prospectively
Last Modified On: 30/12/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Surgical/Anesthesia 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Comparative study of Combination of dexmedetomidine with bupivacaine,lidobupivacaine and ropivacaine 
Scientific Title of Study   Comparative study of the effects of dexmedetomidine added as adjuvant to bupivacaine,levobupivacaine and ropivacaine in brachial plexus blocks: a prospective randomised triple blind study 
Trial Acronym  BLRBB 
Secondary IDs if Any  
Secondary ID  Identifier 
Nil  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ramanareddy MV 
Designation  Associate Professor 
Affiliation  Gayatri Vidya Parishad Institute of Health Care and Medical Technology 
Address  Department of Anaesthesiology ICU OT complex Room No 10 Gayatri Vidya Parishad Institute of Health Care and Medical Technology 6 25 Maridi valley Marikavalasa Madhurawada Visakhapatnam
Department of Anaesthesiology ICU OT complex Room No 10 Gayatri Vidya Parishad Institute of Health Care and Medical Technology 6 25 Maridi valley Marikavalasa Madhurawada Visakhapatnam
Visakhapatnam
ANDHRA PRADESH
530048
India 
Phone  9908232415  
Fax  0891-2590131  
Email  drramanareddymoolagani@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Ramanareddy MV 
Designation  Associate Professor 
Affiliation  Gayatri Vidya Parishad Institute of Health Care and Medical Technology 
Address  Department of Anaesthesiology ICU OT complex Room No 10 Gayatri Vidya Parishad Institute of Health Care and Medical Technology 6 25 Maridi valley Marikavalasa Madhurawada Visakhapatnam
Department of Anaesthesiology ICU OT complex Room No 10 Gayatri Vidya Parishad Institute of Health Care and Medical Technology 6 25 Maridi valley Marikavalasa Madhurawada Visakhapatnam
Visakhapatnam
ANDHRA PRADESH
530048
India 
Phone  9908232415  
Fax  0891-2590131  
Email  drramanareddymoolagani@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Ramanareddy MV 
Designation  Associate Professor 
Affiliation  Gayatri Vidya Parishad Institute of Health Care and Medical Technology 
Address  Department of Anaesthesiology ICU OT complex Room No 10 Gayatri Vidya Parishad Institute of Health Care and Medical Technology 6 25 Maridi valley Marikavalasa Madhurawada Visakhapatnam
Department of Anaesthesiology ICU OT complex Room No 10 Gayatri Vidya Parishad Institute of Health Care and Medical Technology 6 25 Maridi valley Marikavalasa Madhurawada Visakhapatnam
Visakhapatnam
ANDHRA PRADESH
530048
India 
Phone  9908232415  
Fax  0891-2590131  
Email  drramanareddymoolagani@gmail.com  
 
Source of Monetary or Material Support  
Gayatri Vidya Parishad Institute of Health Care and Medical Technology 
 
Primary Sponsor  
Name  Dr Ramana Reddy MV 
Address  Department of Anaesthesiology ICU OT complex Room No 10 Gayatri Vidya Parishad Institute of Health Care and Medical Technology 6 25 Maridi valley Marikavalasa Madhurawada Visakhapatnam  
Type of Sponsor  Other [Individual] 
 
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 
Dr Ramana Reddy M V  GVP Medical College  Room No 12 1st Floor OT Complex Visakhapatnam ANDHRA PRADESH Visakhapatnam ANDHRA PRADESH
Visakhapatnam
ANDHRA PRADESH 
9908232415
0891-2590131
drramanareddymoolagani@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
IECGVPIHCMT  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: M968||Other intraoperative and postprocedural complications and disorders of musculoskeletal system, not elsewhere classified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  bupivacaine  Our study is a 4 arm study, the comparator agent in our study is bupivacaine0.5% alone in the 4th arm of our study 
Intervention  Dexmedetomidine, bupivacaine,levobupivacaine and ropivacaine  Our study is a 4 arm study, the intervension agents in our study are dexmedetomidine+ bupivacaine 0.5%, dexmedetomidine + levobupivacaine 0.5% and dexmedetomidine + ropivacaine 0.75% in the 1st 2nd and 3rd arms respectively and bupivacaine0.5% alone in the 4th arm of our study  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  Eighty adult patients of age 18 and 80 yrs of either sex with weight betweeen 50 and 80kg and who were of American Society of Anaesthesiologists (ASA) grade I and II, attending our medical college hospital for surgeries of upper limb between the period 01-1-2021 and 31-08-2021 to be enrolled in this study 
 
ExclusionCriteria 
Details  Exclusion criteria adapted for our study were patients with known allergy to study drugs, patient refusal of local anaesthetic block, patients suffering from neurological disorders, psychiatric disorders, mental retardation, uncontrolled hypertension and diabetes mellitus, coagulation or bleeding abnormalities,pregnant women and lactating mothers, patients on adrenergic agonist/antagonist medications and infection at the site of the block.  
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
The primary outcome variables studied were the differences in the duration of the analgesia and the duration of motor and sensory block  Sensory and motor block blockade was assessed every 2 min intervals for the initial 30 min and at 15 minute intervals till completion of surgery and in the first 24 hours of postoperative period 
 
Secondary Outcome  
Outcome  TimePoints 
The secondary outcome will be the differences in the duration of onset of the motor and sensory block, fluctuations in haemodynamic variables like heart rate (HR), mean arterial pressure (MAP),respiratory rate( RR) and arterial oxygen saturation (SaO2), total dose of rescue analgesics administered during the 1st 24 hours of post operative period, Ramsay sedation score, surgeon assessment score and patient satisfaction score and any adverse events and drug-related side effects.   At every 5 minute intervals after completion of the block till completion of the surgery and at 30 minute intervals thereafter till 1st 24 hours of post operative period 
 
Target Sample Size   Total Sample Size="80"
Sample Size from India="80" 
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   Phase 4 
Date of First Enrollment (India)   01/01/2021 
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="0"
Months="8"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   Propose to publish in JOACP after completion of the study 
Individual Participant Data (IPD) Sharing Statement

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

Response - YES
  1. What data in particular will be shared?
    Response - All of the individual participant data collected during the trial, after de-identification.

  2. What additional supporting information will be shared?
    Response -  Study Protocol
    Response - Informed Consent Form

  3. Who will be able to view these files?
    Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.

  4. For what types of analyses will this data be available?
    Response - For individual participant data meta-analysis.

  5. By what mechanism will data be made available?
    Response - Proposals should be directed to [drramanareddymoolagani@gmail.com].

  6. For how long will this data be available start date provided 01-09-2021 and end date provided 15-09-2024?
    Response - Beginning 9 months and ending 36 months following article publication.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - Nil
Brief Summary  

INTRODUCTION

            In our institution, most of the surgeries on upper limb ( hand, fore-arm and elbow) are performed under brachial plexus blocks usually through supra-clavicular approach using a mixture of 0.5% bupivacaine and 2 % lidocaine. Bupivacaine is  a racemic mixture of two stereoenantiomers dextrobupivacaine and levobupivacaine and provides long duration of action but its main disadvantage is because of its central nervous system  and cardiotoxic effects

In view of the above facts there is a trend to switch over to safer alternative anaesthetic agents like levo-bupivacaine and ropivacaine.  

            Levobupivacaine, an S-enantiomer of bupivacaine  has been reported to have a longer duration of analgesic effect compared with ropivacaine when used for spinal and epidural anesthesia]  and  has favorable clinical profile and lesser cardiotoxicity when compared with racemic bupivacaine

            Several adjuvants  such as dexmedetomidine (DMT),clonidine, fentanyl, etc are used in combination with local anaesthetic agents  to enhance their  blocking potential, thereby decreasing the time of onset of the block and increasing  the duration of the motor and sensory block. In this context, Alpha-2-adrenergic receptor (α2-AR) agonist, DMT is emerging as the most popular adjuvant.

DMT is being safely used as an adjuvant for subarachnoid blocks in urological surgeries, orthopaedic procedures of lower limb and lower abdominal surgical procedures,[27]

 

 We hypothesized that addition of DMT as adjuvant to ropivacaine and levo-bupivacaine  can enhance the block characteristics by extending the duration of analgesia into the post operative period. Accordingly we undertook the present study to evaluate and compare the block characteristics of 0.5% bupivacaine, 0.5% levo-bupivacaine, 0.75% ropivacaine with dexmedetomidine added as adjuvant versus  0.5% bupivacaine alone i.e. without DMT added an adjuvant. In our study we added DMT in a dose of  0.5 µg/kg body weight to the local anaesthetic agents used in the brachial plexus blocks performed through supraclavicular approach.

METHOD

Institutional Ethical Committee approval was obtained vide RC. No:GVPIHCMT/IEC/20201208/02 dated 08-12-2020 of Dean, GVPIHCMT, Visakhapatnam Eighty adult patients of age  18 and 80 yrs of either sex with weight betweeen 50 and 80kg and who  were of American Society of Anaesthesiologists (ASA) grade I and II, attending our medical college hospital for surgeries of upper limb were enrolled in this study, to be undertaken between the period 01-1-2021 and 31-08-2021. Written Informed consent was obtained from all the participants after explaining in detail about the study protocol and all consequent risks and benefits in their mother tongue in the presence of two witnesses. Exclusion criteria adapted for our study were patients with known allergy to study drugs, patient refusal of local anaesthetic block, patients suffering from neurological disorders, psychiatric disorders, mental retardation, uncontrolled hypertension and diabetes mellitus, coagulation or bleeding abnormalities,pregnant women and lactating mothers, patients on adrenergic agonist/antagonist medications and infection at the site of the block. 

Patients  were  randomly allocated to four groups of 20 each (n=20) by utilizing computer generated random grouping software: group B, group L, group R and group C and  a  sequentially numbered sealed opaque envelope method was  utilized for allocating the  individual patient to the respective study group. The anaesthetic drug mixture for the brachial plexus block was  prepared as per given schedule below by an anaesthesiologist who was further excluded from participating in patient assessment.

Patients of group B (n=20) were given  30 ml of  0.5% bupivacaine  plus 0.5 µg/Kg body weight of DMT; Patients of group L (n=20) were given  30 ml of  0.5% levo-bupivacaine  plus 0.5 µg/Kg body weight of DMT; patients of group R (n=20)  were given 30 ml of  0.75% ropivacaine  plus 0.5 µg/Kg body weight of DMT and patients of  group C (n=20, )   were given 30 ml of  0.5% bupivacaine alone and this group served as control arm for our study.

            The primary outcome variables studied were the differences in the duration of the analgesia and the duration of motor and sensory  block.  The secondary outcome variables studied was were the differences in the duration of onset of the motor and sensory  block, fluctuations  in haemodynamic variables like  heart rate (HR), mean arterial pressure (MAP),respiratory rate( RR) and arterial oxygen saturation (SaO2),  total dose of rescue analgesics administered during the 1st 24 hours of post operative period, Ramsay sedation score, surgeon assessment score and  patient satisfaction score and any adverse events and drug-related side effects.

Brachial plexus block was  performed through  supraclavicular approach by an experienced anaesthesiologist different from the one assessing the patient intra‑ and post‑operatively and collecting the data for analysis.

Sensory and motor block blockade was assessed every 2 min intervals for the initial 30 min. Sensory block was  tested by a pinprick sensation using a 23‑G needle in entire dermatomes innervated by median , radial , ulnar  and musculo cutaneous nerves. Onset of sensory block  was  considered when there was  a dull sensation to pin prick along the distribution of any of these nerves. Complete sensory block was considered when there was a complete loss of sensation to pin prick. Degree of sensory block was  graded as[29] Grade: 0 when sharp sensation of pin prick is  felt, Grade: 1, if analgesia and dull sensation is  felt and Grade: 2 when fully anaesthetised  and no sensation is  felt.

The duration of sensory block was  defined as the time interval between the onset of sensory anaesthesia and the complete resolution of anaesthesia on all the  nerve territories. The duration of motor block was defined as the time interval between the onset of motor block and the recovery of complete motor function of the hand and forearm.

 

Postoperatively, the patients were transferred to the recovery room for further monitoring. Pain was assessed by VNRS at every 30 min for 6 h, and then at every 1 hour till the patients complain of pain (VNRS  >3). Patients were enquired regarding their satisfaction level about the anaesthetic experience on a 3 point patient assessment score.[32] (score 1= extremely dissatisfied -had severe pain and or other adverse events; score 2 = satisfied- had minimal pain only; score = 3 extremely satisfied, no pain or adverse events and comfortable during block and surgery).

Power analysis and sample size calculation  were based on a population standard deviation of one with respect to the duration of the sensory block  derived from  the  results of previous studies. With 80% power and 5% alpha error to detect a difference in duration of the sensory block of one hour between groups, a sample size of 15 patients per group was required. We included 20 patients in each group for better validation of results and to compensate for any dropouts in the middle of the study due to incomplete blocks. At the end of the study, all the data were compiled using Microsoft excel programme and the quantitative variables (parametric data)  were presented as mean ± SD and ordinal / nominal/categorical data (non parametric data) were presented as number and percentage. The differences between the groups  were  analysed using ANOVA, Variance ratio test  and an appropriate  Post Hoc test for comparison between the groups whenever required. Chi square test was  used for non parametric data. Statistical analysis was  carried out using Microsoft Windows Excel 2007 and SPSS version 20.0 IBM and a P value of ≤ 0.05 was  considered as statistically significant. 

 
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