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

NCT05198622 | Unknown DMC

• 1 other identifier: IRB-21-28
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Chronic Pain; Intercostobrachial Nerve Injury

Keywords

Chronic Pain; Breast Surgery; Breast Cancer; Intercostobrachial Nerve Injury

Outcome Measures

Primary Outcomes (4)

• Persistent Post-Surgical Pain (PPSP) using Brief Pain Inventory-Short Form (BPI SF)

  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)

  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)

  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)

  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 Outcomes (7)

• Health Related Quality of Life using Functional Assessment of cancer therapy-Breast form (FACT-B)

  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

  Baseline (Pre-Operatively), 2 weeks (Post-Operatively), 3 months (Post-Operatively) and 6 months (Post-Operatively)

• Operating Time (Minutes)

  Intraoperative

• Lymph Node Yield

  Intraoperative

• Post-Operative Complications as per Clavien Dindo Classification (CDC)

  From the time of intervention to 30 days (Post-Operatively)

Study Arms (2)

Intercostobrachial Nerve Preservation Arm

EXPERIMENTAL

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

Intercostobracial Nerve Sacrifice Arm

ACTIVE COMPARATOR

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

Interventions

Intercostobrachial Nerve Preserving Axillary Lymph Node Dissection PROCEDURE

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.

Intercostobrachial Nerve Preservation Arm

Intercostobrachial Nerve Sacrificing Axillary Lymph Node Dissection PROCEDURE

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.

Intercostobracial Nerve Sacrifice Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shaukat Khanum Memorial Cancer Hospital & Research Centre: lead

Study Sites (1)

Shaukat Khanum Memorial Cancer Hospital & Research Centre

Lahore, Punjab Province, 54000, Pakistan

Location

Related Publications (11)

• Wang L, Cohen JC, Devasenapathy N, Hong BY, Kheyson S, Lu D, Oparin Y, Kennedy SA, Romerosa B, Arora N, Kwon HY, Jackson K, Prasad M, Jayasekera D, Li A, Guarna G, Natalwalla S, Couban RJ, Reid S, Khan JS, McGillion M, Busse JW. Prevalence and intensity of persistent post-surgical pain following breast cancer surgery: a systematic review and meta-analysis of observational studies. Br J Anaesth. 2020 Sep;125(3):346-357. doi: 10.1016/j.bja.2020.04.088. Epub 2020 Jun 28.

  PMID: 32611524 BACKGROUND

• Richebe P, Capdevila X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations. Anesthesiology. 2018 Sep;129(3):590-607. doi: 10.1097/ALN.0000000000002238.

  PMID: 29738328 BACKGROUND

• Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009 Sep;10(9):895-926. doi: 10.1016/j.jpain.2009.06.012.

  PMID: 19712899 BACKGROUND

• Abdullah TI, Iddon J, Barr L, Baildam AD, Bundred NJ. Prospective randomized controlled trial of preservation of the intercostobrachial nerve during axillary node clearance for breast cancer. Br J Surg. 1998 Oct;85(10):1443-5. doi: 10.1046/j.1365-2168.1998.00843.x.

  PMID: 9782034 BACKGROUND

• Torresan RZ, Cabello C, Conde DM, Brenelli HB. Impact of the preservation of the intercostobrachial nerve in axillary lymphadenectomy due to breast cancer. Breast J. 2003 Sep-Oct;9(5):389-92. doi: 10.1046/j.1524-4741.2003.09505.x.

  PMID: 12968959 BACKGROUND

• Salmon RJ, Ansquer Y, Asselain B. Preservation versus section of intercostal-brachial nerve (IBN) in axillary dissection for breast cancer--a prospective randomized trial. Eur J Surg Oncol. 1998 Jun;24(3):158-61. doi: 10.1016/s0748-7983(98)92793-7.

  PMID: 9630850 BACKGROUND

• Kaur N, Kumar R, Jain A, Saxena AK. Sensory Changes and Postmastectomy Pain Following Preservation of Intercostobrachial Nerve in Breast Cancer Surgery: a Prospective Randomized Study. Indian J Surg Oncol. 2021 Mar;12(1):108-113. doi: 10.1007/s13193-020-01193-5. Epub 2020 Sep 5.

  PMID: 33814840 BACKGROUND

• Taira N, Shimozuma K, Ohsumi S, Kuroi K, Shiroiwa T, Watanabe T, Saito M. Impact of preservation of the intercostobrachial nerve during axillary dissection on sensory change and health-related quality of life 2 years after breast cancer surgery. Breast Cancer. 2014 Mar;21(2):183-90. doi: 10.1007/s12282-012-0374-x. Epub 2012 Aug 30.

  PMID: 22932759 BACKGROUND

• Chirappapha P, Arunnart M, Lertsithichai P, Supsamutchai C, Sukarayothin T, Leesombatpaiboon M. Evaluation the effect of preserving intercostobrachial nerve in axillary dissection for breast cancer patient. Gland Surg. 2019 Dec;8(6):599-608. doi: 10.21037/gs.2019.10.06.

  PMID: 32042666 BACKGROUND

• Tan G, Jensen MP, Thornby JI, Shanti BF. Validation of the Brief Pain Inventory for chronic nonmalignant pain. J Pain. 2004 Mar;5(2):133-7. doi: 10.1016/j.jpain.2003.12.005.

  PMID: 15042521 BACKGROUND

• Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, Deasy S, Cobleigh M, Shiomoto G. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument. J Clin Oncol. 1997 Mar;15(3):974-86. doi: 10.1200/JCO.1997.15.3.974.

  PMID: 9060536 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Chronic Pain

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Dr. Ibtissam Bin Khalid, MBBS

  Shaukat Khanum Memorial Cancer Hospital & Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2022
• First Posted: January 20, 2022
• Study Start: January 30, 2022
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: February 1, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)