Can Chronic Post-surgical Pain be Reduced by Preserving Intercostobrachial Nerve During Axillary Lymph Node Dissection? : A Randomized Controlled Trial (PAINE)

January 30, 2022 updated by: Dr. Ibtissam Bin Khalid, Shaukat Khanum Memorial Cancer Hospital & Research Centre

Intercostobrachial nerve (ICBN) is a cutaneous nerve that provides sensation to the lateral chest, upper medial arm and axilla. It arises from the second intercostal nerve and leave intercostal space at the level of midaxillary line. It then pierces the serratus anterior muscle and enters axilla. Intercostobrachial nerve is encountered during axillary lymph node dissection (ALND) while mobilizing axillary contents laterally off the chest wall and tends to tether axillary contents to the lateral chest wall. Many surgeons routinely sacrifice it as doing so makes mobilization easier and allow exposure of long thoracic neve. Currently there is no consensus on the usefulness of preserving intercostobrachial nerve.

According to a 2020 systemic review and meta-analysis, prevalence of CPSP/ PPSP following breast cancer surgery ranged from 2% to 78% and pooled prevalence was found to be 35%. Higher prevalence was associated with ALND. Several risk factors have been identified which contribute to the development of PPSP. These include; Preexisting pain, preoperative opioid exposure, genetics, psychological factors such as anxiety, depression or catastrophizing, intensity of acute postoperative pain and nerve injury during surgery.

As a result of nerve injury, damaged and non-damaged nerve fibers start generating action potential spontaneously. These are considered ectopic inputs as they do not arise from peripheral terminals. These inputs lead to the development of central sensitization, which is a state of exaggerated functional response of neurons involved in the pain pathway. This increased sensitization results due to increased membrane excitability, enhanced synaptic efficacy and decreased inhibition.

The aim of the present trial is to investigate the effect of ICBN preservation on chronic/ persistent post surgical pain (CPSP/ PPSP). This will be achieved through a randomized control trial with CPSP/ PPSP as a primary outcome measure. Secondary outcome measures will include Health Related Quality of Life (HRQoL), operating time, lymph node yield, functional status of ipsilateral shoulder, post-operative complications and post-operative use of opioid analgesics.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

182

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Punjab
      • Lahore, Punjab, Pakistan, 54000
        • Shaukat Khanum Memorial Cancer Hospital & Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Aged 18 or above.
  • Known cases of invasive breast Cancer.
  • Undergoing Axillary Lymph Node Dissection (ALND) alone, ALND with mastectomy or ALND with breast conservation surgery (BCS)
  • Capacity to give informed consent

Exclusion Criteria:

  • Chronic diseases limiting motion of shoulder such as neuropathies, history of trauma and autoimmune diseases.
  • Patients undergoing redo axillary lymph node dissection.
  • Patients undergoing bilateral axillary lymph node dissection.
  • History of chronic pain lasting more than 3 months. Potential causes include: arthritis, backache, fibromyalgia, Irritable bowel disease, irritable bowel syndrome and different types of headache.
  • M1 stage of the TNM staging system at the time of initial diagnosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intercostobrachial Nerve Preservation Arm
Intercostobrachial nerve preserving axillary lymph node dissection will be carried out. Post-operatively, the patients will be monitored in the post anesthesia care unit (PACU). Acute Post-Operative pain will be controlled using a standardized pain management regimen in accordance with World Health Organization (WHO) analgesia ladder. The patients will be discharged from PACU and admitted to surgical ward once numerical rating score (NRI) is below 4.
Procedure: Intercostobrachial Nerve Preserving Axillary Lymph Node Dissection

A single standardized technique will be used in all of the patients. For patients undergoing mastectomy, ALND will be carried out using the incision given for mastectomy. A separate incision may be required for patients undergoing breast conservation surgery. Flaps of skin and subcutaneous tissue will be raised and dissection will be carried out till the edge of pectoralis major muscle. Clavipectoral fascia will be opened to gain access to axillary fat and the nodes. These will be removed en block and the intercostobrachial nerve will be completely preserved during this dissection.

All of the surgeons carrying out the intervention would have completed formal training (Fellowship Level) in breast surgery.
Active Comparator: Intercostobracial Nerve Sacrifice Arm
Intercostobrachial nerve sacrificing axillary lymph node dissection will be carried out. Post-operatively, the patients will be monitored in the post anesthesia care unit (PACU). Acute Post-Operative pain will be controlled using a standardized pain management regimen in accordance with World Health Organization (WHO) analgesia ladder. The patients will be discharged from PACU and admitted to surgical ward once numerical rating score (NRI) is below 4.
Procedure: Intercostobrachial Nerve Sacrificing Axillary Lymph Node Dissection

A single standardized technique will be used in all of the patients. For patients undergoing mastectomy, ALND will be carried out using the incision given for mastectomy. A separate incision may be required for patients undergoing breast conservation surgery. Flaps of skin and subcutaneous tissue will be raised and dissection will be carried out till the edge of pectoralis major muscle. Clavipectoral fascia will be opened to gain access to axillary fat and the nodes. These will be removed en block and the intercostobrachial nerve will be sacrificed during this dissection.

All of the surgeons carrying out the intervention would have completed formal training (Fellowship Level) in breast surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Persistent Post-Surgical Pain (PPSP) using Brief Pain Inventory-Short Form (BPI SF)
Time Frame: Baseline (Pre-Operatively)

BPI SF is a validated tool for the measurement of chronic pain. It assesses average pain intensity over the past 24 hour period. It defines pain as follows:

Mild Pain: Score 1-4 Moderate Pain: Score 5-6 Severe Pain: Score 7-10 Recall Period: Last 24 hours
Baseline (Pre-Operatively)
Persistent Post-Surgical Pain (PPSP) using Brief Pain Inventory-Short Form (BPI SF)
Time Frame: 2 Weeks (Post-Operatively)

BPI SF is a validated tool for the measurement of chronic pain. It assesses average pain intensity over the past 24 hour period. It defines pain as follows:

Mild Pain: Score 1-4 Moderate Pain: Score 5-6 Severe Pain: Score 7-10 Recall Period: Last 24 hours
2 Weeks (Post-Operatively)
Persistent Post-Surgical Pain (PPSP) using Brief Pain Inventory-Short Form (BPI SF)
Time Frame: 3 Months (Post-Operatively)

BPI SF is a validated tool for the measurement of chronic pain. It assesses average pain intensity over the past 24 hour period. It defines pain as follows:

Mild Pain: Score 1-4 Moderate Pain: Score 5-6 Severe Pain: Score 7-10 Recall Period: Last 24 hours
3 Months (Post-Operatively)
Persistent Post-Surgical Pain (PPSP) using Brief Pain Inventory-Short Form (BPI SF)
Time Frame: 6 Months (Post-Operatively)

BPI SF is a validated tool for the measurement of chronic pain. It assesses average pain intensity over the past 24 hour period. It defines pain as follows:

Mild Pain: Score 1-4 Moderate Pain: Score 5-6 Severe Pain: Score 7-10 Recall Period: Last 24 hours
6 Months (Post-Operatively)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Health Related Quality of Life using Functional Assessment of cancer therapy-Breast form (FACT-B)
Time Frame: Baseline (Pre-Operatively), 2 weeks (Post-Operatively), 3 months (Post-Operatively) and 6 months (Post-Operatively)

FACT-B is a 37 item, validated tool for the measurement of health of health related quality of life (HRQoL). It consists of five subscales: Physical well being, emotional well being, social well being, functional well being and a breast cancer-specific subscale. Items are rated from 0 (not at all) to 4 (very much) and a total score is calculated. The total score ranges from 0-148. Lower score indicates a better health related quality of life.

Recall Period: Last 7 Days
Baseline (Pre-Operatively), 2 weeks (Post-Operatively), 3 months (Post-Operatively) and 6 months (Post-Operatively)
Functional Status of Ipsilateral Shoulder using Shoulder Pain and Disability Index (SPADI) Questionnaire
Time Frame: Baseline (Pre-Operatively), 2 weeks (Post-Operatively), 3 months (Post-Operatively) and 6 months (Post-Operatively)

SPADI is a validated tool for the measurement of shoulder pain and disability. It is composed of pain component and functional assessment component. Each item in score component is rated from 0 (no pain) to 10 (worst imaginable pain) whereas items in functional assessment component are rated from 0 (no difficulty) to 10 (so difficult it requires help). The total score is expressed as a percentage. A higher score indicates more disability.

Recall Period: Last 7 Days
Baseline (Pre-Operatively), 2 weeks (Post-Operatively), 3 months (Post-Operatively) and 6 months (Post-Operatively)
Operating Time (Minutes)
Time Frame: Intraoperative
Operating Time is the time duration from incision to the closure. It will be measured in minutes.
Intraoperative
Lymph Node Yield
Time Frame: Intraoperative
Lymph node yield is the total number of benign or malignant lymph nodes found in the axillary lymph node dissection specimen at the time of histopathological analysis.
Intraoperative
Post-Operative Complications as per Clavien Dindo Classification (CDC)
Time Frame: From the time of intervention to 30 days (Post-Operatively)

Clavien Dindo Classification divides the severity of post-operative complications based on the level of medical intervention needed. CDC is as following:

Grade I: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgesics, diuretics, electrolytes and physiotherapy. This Grade also includes wound infections opened at the bedside.

Grade II: Requiring pharmacological treatment with drugs other than such allowed for Grade I complications. Blood transfusions and total parenteral nutrition are also included.

Grade III (a): intervention not under general anesthesia Grade III (b): intervention under general anesthesia Grade IV: Life-threatening complication (including complications of the Central Nervous System) requiring Intermediate Care/Intensive Care Unit management Grade V: Death of a patient
From the time of intervention to 30 days (Post-Operatively)
Post-Operative usage of Opioid Analgesics
Time Frame: 2 weeks (Post-Operatively), 3 months (Post-Operatively) and 6 months (Post-Operatively)
Type of opioid analgesic and prescribed daily dose in the post-operative period
2 weeks (Post-Operatively), 3 months (Post-Operatively) and 6 months (Post-Operatively)
Adverse Events
Time Frame: From the time of intervention to 6 months (Post-Operatively)
All adverse events will be documented on case report forms. The data management committee (DMC) will review these adverse events and determine if these are due to the intervention.
From the time of intervention to 6 months (Post-Operatively)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shaukat Khanum Memorial Cancer Hospital & Research Centre

Investigators

  • Principal Investigator: Dr. Ibtissam Bin Khalid, MBBS, Shaukat Khanum Memorial Cancer Hospital & Research Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2022

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

October 1, 2022

Study Registration Dates

First Submitted

January 9, 2022

First Submitted That Met QC Criteria

January 18, 2022

First Posted (Actual)

January 20, 2022

Study Record Updates

Last Update Posted (Actual)

February 1, 2022

Last Update Submitted That Met QC Criteria

January 30, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-21-28

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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