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CTRI Number  CTRI/2024/06/068748 [Registered on: 12/06/2024] Trial Registered Prospectively
Last Modified On: 11/06/2024
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Surgical/Anesthesia 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   The effect of intrathecal morphine on postoperative Natural Killer Cell activity in patients undergoing surgery for pancreatobiliary cancers. 
Scientific Title of Study   The effect of intrathecal morphine on postoperative Natural Killer Cell activity in patients undergoing abdominal surgery for pancreatobiliary malignancy:A randomized control trail. 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
AIIMS/IEC/2024/5076/08-04-2024  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Srinivas Sudheendra Avadhani 
Designation  PG Student 
Affiliation  All India Institute of Medical Sciences,Jodhpur  
Address  Department of Anaesthesiology and Critical Care, 3rd floor, DnT block, All India Institute of Medical Sciences (AIIMS), HI Area phase II, Basni, Jodhpur, RAJASTHAN. 342005 India

Jodhpur
RAJASTHAN
342005
India 
Phone  9900487461  
Fax    
Email  srinivasavadhani444@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Priyanka Sethi  
Designation  Additional professor 
Affiliation  All India Institute of Medical Sciences, Jodhpur 
Address  Department of Anaesthesiology and Critical Care , 3rd floor, DnT block, All India Institute of Medical Sciences (AIIMS), HI Area phase II, Basni, Jodhpur, RAJASTHAN. 342005 India

Jodhpur
RAJASTHAN
342005
India 
Phone  9352206300  
Fax    
Email  dr.priyanka_sethi@yahoo.co.in  
 
Details of Contact Person
Public Query
 
Name  Dr Priyanka Sethi  
Designation  Additional professor 
Affiliation  All India Institute of Medical Sciences, Jodhpur 
Address  Department of Anaesthesiology and Critical Care , 3rd floor, DnT block, All India Institute of Medical Sciences (AIIMS), HI Area phase II, Basni, Jodhpur, RAJASTHAN. 342005 India

Jodhpur
RAJASTHAN
342005
India 
Phone  9352206300  
Fax    
Email  dr.priyanka_sethi@yahoo.co.in  
 
Source of Monetary or Material Support  
All India Institute Of Medical Sciences Jodhpur (AIIMS), HI Area phase II, Basni, Jodhpur, RAJASTHAN. 342005 India 
 
Primary Sponsor  
Name  All India Institute Of Medical Sciences Jodhpur 
Address  All India Institute Of Medical Sciences AICU 3rd Floor Emergency Building DnT Block Jodhpur RAJASTHAN 342005  
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 Srinivas Sudheendra Avadhani  All India Institute of Medical Sciences, Jodhpur  Department of Anaesthesiology and Critical Care, 3rd floor, DnT block, AIIMS Hospital, Basni Phase II , Jodhpur, RAJASTHAN
Jodhpur
RAJASTHAN 
9900487461

srinivasavadhani444@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
AIIMS, Jodhpur  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 
Intervention  Intrathecal morphine   200μg morphine will be administered to the intrathecal space before induction of General Anaesthesia in the operating room. 
Comparator Agent  Sham procedure   Pressure will be applied to the anesthetized skin with a capped syringe without dural puncture before induction of General Anaesthesia in the operating room. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  All patients aged 18 to 65years (American society of anaesthesiologist grading I, II, III) to be taken upfront for major abdominal surgeries for pancreatobiliary malignancy.
 
 
ExclusionCriteria 
Details  1.Patients with ASA grade greater than 3.
2.Patients having chronic pain or any opioid treatment.
3.Patients expected to be requiring postoperative ventilation support.
4.Patients with pre-existing immunodeficiency.
5.Any ongoing infections in patient.
6.Any other chronic inflammatory conditions such as Rheumatoid Arthritis etc.
7.Patients on chemotherapy or radiotherapy.
8.History of blood transfusion in last 15 days
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To measure effect of, addition of intrathecal morphine to post operative pain management regime, on postoperative Natural Killer Cell quantity in patients posted for pancreato-biliary malignancy surgery.  24 hours 
 
Secondary Outcome  
Outcome  TimePoints 
To assess time for first rescue analgesia in both the study groups.   24hours 
To assess Patient satisfaction score using likert scale.  24hours  
To calculate total opioid consumption post operatively in both study groups.  24hours 
To assess Pain using NRS score following surgery at 6th, 12th, 24th, 36th, 48th hour post operatively.  48hours 
To report any side effects like postoperative nausea and vomiting etc.  24hours 
To measure the effect on Serum CRP levels postoperatively.   24hours 
To assess Quality of recovery using QOR 15 Score postoperatively.   24hours 
 
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)   24/06/2024 
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="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

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

Response - NO
Brief Summary  

Pain is a complex and subjective experience that involves both sensory and emotional components. It is characterized as an unpleasant sensation associated with actual or potential tissue damage. Acute pain refers to pain that lasts for a short duration, typically not exceeding three months. During the perioperative period, acute pain can occur due to the trauma of surgery, inflammation, and overactivity of the sympathetic nervous system. If not effectively managed, acute pain can progress to chronic persistent post-surgical pain.

Studies on animals consistently suggest that poorly controlled pain after surgery can lead to immunosuppression and potentially enhance the development of malignant processes. The most significant effect of this immunosuppression is a decrease in the count and activity of Natural Killer (NK) cells. Additionally, morphine, commonly used for pain management, has been found to have immunosuppressive effects. This may pose a risk for patients who have undergone surgery, as a suppressed immune system can make them more vulnerable to postoperative infections and hinder defense against malignant tumors.

Uncontrolled acute perioperative pain can also amplify the surgical stress response. The enhanced activity in the sympathetic nervous system and neuroendocrine responses can further decrease Natural Killer cell activity, potentially increasing the risk of cancer recurrence and metastasis. Natural Killer cells play a crucial role in recognizing and eliminating tumor cells without relying on specific antigens, making them a primary defense mechanism against tumor development and metastases.

To evaluate the effects of intrathecal morphine on immune processes in surgery, we are conducting investigations on Natural Killer cell activity using immunological tests. Additionally, pain control without excessive opioid consumption is a challenge for physicians. Intrathecal morphine (ITM) has emerged as a promising alternative that can improve patient outcomes. This is particularly relevant for postoperative analgesia following pancreatobiliary cancer surgery, which often poses challenges due to insufficient pain management.

Intrathecal anaesthesia offers a simpler and quicker alternative to epidural anaesthesia, with a lower rate of technical failure. Similar to epidural analgesia, intrathecal morphine has demonstrated efficacy in improving postoperative pain scores and reducing the need for rescue analgesia after major abdominal cancer surgery. This is important considering the significant postoperative pain experienced by patients undergoing definitive surgery for pancreatobiliary malignancies.

While intravenous patient-controlled analgesia (IV PCA) and continuous epidural analgesia have been considered standard analgesic modalities for abdominal surgery in patients with malignancies, their use can be controversial.

Our study will compare, effect of addition of intrathecal morphine on post operative pain regime of pancreato-biliary malignancy, on quantity of Natural killer cells. We will also compare the cumulative 24-hour IV opioid consumption during the postoperative period between patients who received ITM and those who underwent sham procedures. In addition to pain severity, we will examine variables relating to postoperative recovery profiles, complications, duration of hospital stay, and the impact on serum C-reactive protein (CRP) levels as secondary outcomes. These findings will contribute to our understanding of the immune and pain management processes in perioperative care for patients with pancreatic and biliary malignancies. 
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