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CTRI Number  CTRI/2020/09/027756 [Registered on: 11/09/2020] Trial Registered Prospectively
Last Modified On: 30/09/2021
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Surgical/Anesthesia 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Comparison between pain control techniques, viz, injection of drug in the lower back, ultrasound-guided injection of drug in the upper back and patient-controlled pain management in breast cancer surgery 
Scientific Title of Study   Comparison of the efficacy of intrathecal morphine, ultrasound-guided erector spinae plane block with PCA fentanyl in the control of post-operative pain after modified radical mastectomy: a randomized controlled trial 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Rebecca Lalnunfel Ralsun 
Designation  Junior Resident 
Affiliation  All India Institute of Medical Sciences, New Delhi 
Address  Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029

South West
DELHI
110029
India 
Phone  7896602649  
Fax    
Email  rebeccaralsun777@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Rajeshwari Subramaniam 
Designation  Professor and Head 
Affiliation  All India Institute of Medical Sciences, New Delhi 
Address  Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029

South West
DELHI
110029
India 
Phone  9810079229  
Fax    
Email  drsrajeshwari@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Rebecca Lalnunfel Ralsun 
Designation  Junior Resident 
Affiliation  All India Institute of Medical Sciences, New Delhi 
Address  Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029

South West
DELHI
110049
India 
Phone  7896602649  
Fax    
Email  rebeccaralsun777@gmail.com  
 
Source of Monetary or Material Support  
All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029 
 
Primary Sponsor  
Name  All India Institute of Medical Sciences 
Address  Ansari Nagar, New Delhi - 110029 
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 
Rebecca Lalnunfel Ralsun  All India Institute of Medical Sciences  Main OT Complex and Recovery Area, AIIMS, Ansari Nagar, New Delhi - 110029
South West
DELHI 
7896602649

rebeccaralsun777@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute Ethics Committee, AIIMS  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Control  Skin infiltration with 5ml of 0.125% ropivacaine either at the T4 vertebral level or the skin overlying the L3-L4 interspace with the patient in the sitting position. This will be followed by general anesthesia for the surgery. In the first 24 hours post-operative period, the patient will receive PCA fentanyl. 
Intervention  Intrathecal morphine   Intrathecal Morphine: The patient will be placed in the sitting position, with the spine flexed. After identification of the landmarks, the back will be painted and draped. Using strict aseptic precautions local anesthetic will be infiltrated at the L3-L4 interspace. A 25G Quincke spinal needle will be used to enter the intrathecal space. The entry into the subarachnoid space will be confirmed by the free flow of cerebrospinal fluid (CSF). 200µg preservative-free morphine in 2ml of saline will then be injected. The patient will be made to lie supine immediately after spinal injection of drugs. Blood pressure and heart rate will be monitored immediately after spinal injection of drugs and then every 10 minutes.This will be followed by general anesthesia for the surgery. In the first 24 hours post-operative period, the patient will receive PCA fentanyl. 
Intervention  Ultasound-guided erector spinae plane block  Erector Spinae Plane Block: Under all aseptic conditions ESPB block will be performed with 100 mm 21G block needle under ultrasound (US) guidance using a linear probe with a frequency range of 6-13 MHz in sitting position at T4 vertebral level. The US probe will be placed 2-3 cm lateral to the spinous process in parasagittal plane to identify the transverse process of T4 vertebra and the erector spinae muscle. The needle will be inserted in craniocaudal direction to reach a plane between erector spinae muscle and transverse process, where 20 mL of 0.375 % Ropivacaine will be deposited. This will be followed by general anesthesia for the surgery. In the first 24 hours post-operative period, the patient will receive PCA fentanyl. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Female 
Details  ASA I-II patients scheduled to undergo elective modified radical mastectomy 
 
ExclusionCriteria 
Details  1) Patient refusal for regional techniques
2) All contra-indications to regional techniques:
a) Local or systemic infection
b) Known allergy to the study drugs
c) Bleeding disorders
d) Platelet count <80,000/μL of blood
3) BMI > 35
4) Inability to use PCA device post operatively
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
24-hour fentanyl consumption   From arrival in post-anesthesia care unit to 24 hours post-operatively 
 
Secondary Outcome  
Outcome  TimePoints 
Time to first analgesic requirement  From arrival in post-anesthesia care unit to 24 hours post-operatively 
Post-operative pain parameters: 0-100mm Visual analogue scale (VAS) on abduction of ipsilateral arm above the head  At the time of arrival in post-anesthesia care unit and then at 30 minutes, 1, 2, 4, 6, 12 and 24 hours after operation. 
Patient satisfaction score  At 24 hours after operation 
Incidence of adverse events (Post-operative nausea/vomiting, respiratory depression, pruritus, urinary retention)  From arrival in post-anesthesia care unit to 24 hours post-operatively 
 
Target Sample Size   Total Sample Size="60"
Sample Size from India="60" 
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 2 
Date of First Enrollment (India)   15/09/2020 
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="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

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

Response - NO
Brief Summary   Modified radical mastectomy (MRM) is usually associated with severe post-operative pain and restricted shoulder mobility (1-2). General anesthesia is currently the standard technique used to facilitate MRM but the drawbacks include, but not limited to, inadequate pain control due to lack of residual analgesia, high incidence of nausea and vomiting and increased length of hospital stay (3). Regional analgesia techniques can help in reducing incidence of postsurgical chronic pain (4) as well as cancer recurrence in oncological breast surgeries (5). Although these regional techniques provide varying degree of analgesia, each one is associated with its inherent disadvantages such as failure, limited duration of action, requirement of expertise or specific skills like knowledge of sonoanatomy and ultrasound use, instruments and time, and complications like pneumothorax, vascular puncture and injury to nerves (6).

Erector spinae plane block (ESPB) is one of the newest techniques to be described. ESPB is easy to perform and has low rate of complications (7). However, despite the effectiveness of the technique, further studies are necessary to obtain more evidence of its actions (8).

Intrathecal (IT) opioid administration is commonly used for abdominal and even thoracic surgeries as this procedure is simple, quick, easy to perform and carries a relatively low risk of technical complications or failure. Mazy et al used 25mcg intrathecal fentanyl injected at the lumbar level with 20mg bupivacaine for patients undergoing mastectomy, and reported significant reduction in in 24-hour analgesic requirement and improved range of arm movement (9).

The use of IT opioid especially morphine as an analgesic technique in breast cancer surgeries has not yet been explored. So, we plan to study the post-operative pain parameters, opioid-sparing effect, duration of analgesia and patient satisfaction score between MRM patients receiving intrathecal morphine, those receiving ESPB and those receiving PCA fentanyl alone.

Method: The sample size will be taken as 60 patients, 20 in each group. The patients fulfilling the inclusion criteria will be assigned to three different groups by computer generated random numbers and sequentially numbered opaque sealed envelope technique (SNOSE), namely:
Group A: Intrathecal morphine group
Group B: Erector spinae plane block group
Group C: Control group
On reaching the Operation Room, standard monitors will be attached and intravenous access will be secured. All patients will be given prophylaxis for nausea, vomiting and anxiety. Patients of all groups will receive general anesthesia for the surgery and hemodynamic monitoring will be done vigilantly.
On arriving at Post-anesthesia Care Unit (PACU), device for PCA fentanyl administration will be given to all the patients. Monitors will be attached for hemodynamic monitoring at specific times for the first 24 hours and PCA fentanyl consumption for the 24 hours in the post-operative period will be recorded. Pain will be managed as per standard protocol and in case of severe pain rescue analgesia wll be given. The time to first analgesic requirement by the patient will be recorded, monitored for pain on movement, satisfaction score at the end of first 24 hours will be recorded. In addition, adverse events like nausea, vomiting, respiratory depression will be monitored for and managed accordingly.

References:
1) Ghoncheh M, Pournamdar Z, Salehiniya H. Incidence and Mortality and Epidemiology of Breast Cancer in the World. Asian Pac J Cancer Prev. 2016;17(S3):43-6.
2) Fecho K, Miller NR, Merritt SA, Klauber-Demore N, Hultman CS, Blau WS. Acute and persistent postoperative pain after breast surgery. Pain Med. 2009 Jun;10(4):708-15.
3) Oddby-Muhrbeck E, Jakobsson J, Andersson L, Askergren J. Postoperative nausea and vomiting. A comparison between intravenous and inhalation anesthesia in breast surgery. Acta Anaesthesiol Scand. 1994 Jan;38(1):52-6.
4) Kairaluoma PM, Bachman MS, Rosenberg PH, Pere PJ. Preincisional paravertebral block reduces the prevalence of chronic pain after breast surgery. Anesth Analg. 2006 Sep;103(3):703-8.
5) Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006 Oct;105(4):660-4.
6) Bolin ED, Harvey NR, Wilson SH. Regional anesthesia for breast surgery: techniques and benefits. Curr Anesthesiol Rep 2015;5:217-224.
7) Bartakke AA, Varma MK. Analgesia for Breast Surgery - A Brief Overview. www.wfsahq.org, Anesthesia Tutorial Of The Week 403.
8) Kot P, Rodriguez P, Granell M, Cano B, Rovira L, Morales J, et al. The erector spinae plane block: a narrative review. Korean J Anesthesiol. 2019;72(3):209-20.
9) Mazy AEMA, Saber HIE. Potential analgesia of lumbar intrathecal fetanyl in breast cancer surgery. Research and Opinion in Anesthesia & Intensive Care 2018, 5:220-5.
 
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