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CTRI Number  CTRI/2019/01/017371 [Registered on: 31/01/2019] Trial Registered Prospectively
Last Modified On: 31/01/2019
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug
Surgical/Anesthesia 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   COMPARATIVE EVALUATION OF NEW MUSCLE RELAXANTS IN PATIENTS UNDERGOING ABDOMINAL LAPAROSCOPIC SURGERIES  
Scientific Title of Study   COMPARATIVE EVALUATION OF CISATRACURIUM AND ATRACURIUM IN PATIENTS UNDERGOING ABDOMINAL LAPAROSCOPIC SURGERIES  
Trial Acronym  cisatracurium 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Rohit Bhandari 
Designation  SR 
Affiliation  fortis memorial research institute 
Address  department of anaesthesiology, Fortis Memorial Research Institute, opposite Huda city centre, sector 44

Gurgaon
HARYANA
122002
India 
Phone  9871694267  
Fax    
Email  zibasco@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Hari Hara Dash 
Designation  Professor emeritus 
Affiliation  fortis memorial research institute 
Address  department of anaesthesiology, fortis memorial research institute, sector 44

Gurgaon
HARYANA
122002
India 
Phone    
Fax    
Email  hari.dash@fortishealthcare.com  
 
Details of Contact Person
Public Query
 
Name  Dr Rohit Bhandari 
Designation  SR 
Affiliation  fortis memorial research institute 
Address  department of anaesthesiology, fortis memorial research institute, sector 44

Gurgaon
HARYANA
122002
India 
Phone  9871694267  
Fax    
Email  zibasco@gmail.com  
 
Source of Monetary or Material Support  
Fortis Memorial Research Institute opposite huda city centre sector 44 gurugram 122002 haryana 
 
Primary Sponsor  
Name  Fortis Memorial Research Institute 
Address  Opposite Huda City center, sector 44,gurugram,haryana 122002 
Type of Sponsor  Research institution and hospital 
 
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 Rohit Bhandari  fortis memorial research institute  department of anaesthesiology Fortis Memorial Research Institute opposite huda city centre sector 44 gurugram
Gurgaon
HARYANA 
9871694267

zibasco@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional ethics commitee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: O||Medical and Surgical,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  atracurium  3xED95 dose of atracurium. 0.6mg/kg via intravenous route 
Intervention  cisatracurium  3xED95 dose of cisatracurium. 0.15mg/kg via intravenous route 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Both 
Details  ASA I
ASA II 
 
ExclusionCriteria 
Details  1.Patients refusing to participate in study
2.Patient with neuromuscular diseases
3.Patient taking aminoglycosides, tetracycline
4.Anticipated difficult intubation
5.Patients requiring Rapid Sequence Induction
6.Pregnancy
7.Obese individuals ( BMI > 35)
8.Patients with asthma, atopy and allergic tendencies
9.Patient requiring Emergency surgery
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Other 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
compare clinical profile of cisatracurium and atracurium  1. onset 2. intubating conditions 3. duration of action 4. recovery 
 
Secondary Outcome  
Outcome  TimePoints 
side effects  within first 10 minutes of intubating dose 
 
Target Sample Size   Total Sample Size="50"
Sample Size from India="50" 
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   N/A 
Date of First Enrollment (India)   31/01/2019 
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="3"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   none yet 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  
Discovery of neuromuscular blocking agents was an important landmark for the advancement of anaesthesia. Use of these agents has contributed immensely to rapid developments and growth of different surgical specialties like cardiothoracic surgery, neurosurgery, cancer surgery and management of critical care patients.
Neuromuscular blocking drugs (NMBD) interrupt transmission of nerve impulses at the neuromuscular junction (NMJ), this provides excellent intubating conditions and prevent patient movement to facilitate surgery. Before the advent of muscle relaxants, anaesthesia was induced and maintained by intravenous or inhalation agents only. Tracheal intubation was uncommon, and muscle relaxation if needed was secured by deep inhalation anaesthesia with its attendant risks of respiratory or cardiac depression and recovery was awfully prolonged.
Griffith and Johnson were the first to use curare to provide muscle relaxation during general anaesthesia in 1942, which was a major milestone in the world of anaesthesia. It soon became popular and was used worldwide. Major side effects like histamine release, prolonged duration of action and re-curarization prompted researchers to look for better alternatives. The synthesis of the methonium compounds, and the demonstration of their clinical potential led to increased interest in this field. In 1949, the curariform action of Suxamethonium was described by three independent groups in Italy, Great Britain, and the United States . Suxamethonium had a faster onset of action and provided excellent intubating conditions within a minute which was clinically beneficial in comparison to curare. Since then the use of suxamethonium for securing airway became popular amongst anaesthesiologists. Being a depolarizing agent, suxamethonium produced fasciculations, malignant hyperthermia, rise in serum potassium, post-op myalgia, and repeated dosing posed serious concerns like the appearance of phase II block and arrhythmias. Gallamine (1949), a synthetic nondepolarizing agent became unpopular due to its vagolytic action and cumulative effect. Pancuronium was synthesized in 1964 by Savage and his co-workers, it is long acting and has better neuromuscular blocking properties than d-tubocurarine without any histamine release. Pancuronium slowly became popular in anaesthesia and forced practitioners to neglect curare. As time passed unfavorable cardiac side effects and cumulative effects of pancuronium were unraveled by clinical researchers worldwide. This provided an impetus to the clinical researchers to look for an ideal NMBD. Characteristics of an ‘ideal neuromuscular blocking drug’ are - 1. Non-depolarizing mechanism of action 2. Rapid onset of action 3. Short duration of action 4. Rapid recovery 5. Non-cumulative 6. No cardiovascular side effects 7. No histamine release 8. Reversible by cholinesterase inhibitors 9. High potency 10. Pharmacologically inactive metabolites 11.independent of renal or hepatic function for its elimination. Search for such an agent lead to the discovery of intermediate-acting neuromuscular blocking agents like vecuronium, atracurium, and cisatracurium.
Vecuronium discovered by Savarese and Kitz in 1975 was initially thought to an ideal NMBD. Vecuronium’s favourable cardiac profile, rapid onset of action, and predictable duration of action were soon overshadowed by the major drawbacks like organ dependent elimination and cumulative effect. In 1981 Stenlake and colleagues, in a collaborative Enterprise between the University of Strathclyde and Wellcome Laboratories, synthesized atracurium. It has the advantage over vecuronium as it is eliminated via organ independent Hofmann elimination and ester hydrolysis. Recovery following ED95 dose of atracurium is better than vecuronium. However, atracurium is associated with histamine release and a theoretical risk of acrylate derivatives and laudanosine -a compound which can cross the blood-brain barrier. Even though there is no clinical evidence of adverse effects of laudanosine in humans, in animal studies, it has shown to induce excitement and seizure activity via acetylcholine, glutamate, GABA and opioid receptors.
Cisatracurium, introduced in 1996, is the 1R cis–1′R cis isomer of atracurium comprising approximately 15% of atracurium by weight. It is approximately 3-4 times as potent as atracurium with an ED95 of 0.05 mg/kg during N2O/O2 anaesthesia . Like atracurium, cisatracurium undergoes Hofmann elimination and, therefore, does not depend upon renal or liver function for elimination.  There is no ester hydrolysis of the parent molecule. The principal advantage of cisatracurium is that there has been no evidence of histamine release at doses up to eight times the ED95 whereas atracurium causes histamine release in humans at doses greater than 2.5 times ED95, rendering its usage safe in patients with multiple allergies and bronchial asthma. The production of laudonosine in cisatracurium is negligible in comparison to atracurium.
Cisatracurium is relatively new to the Indian scenario and there is not much clinical data relating to its usage in the Indian population. Our study aims to fill in these gaps in our knowledge. The main objective of this study is to compare neuromuscular blockade and recovery characteristics between the two non-depolarizing neuromuscular blocking drugs; Cisatracurium besylate and atracurium besylate at equipotent doses (3xED95) in adult patients undergoing abdominal laparoscopic surgical procedures with general anaesthesia.
 
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