Clinical trial NCT03421522: Intercostobrachial Nerve Sparing to Reduce Post-Surgical Pain
Official title: Intercostobrachial Nerve Sparing in Breast Cancer Surgery to Reduce Persistent Post-surgical Pain - an International Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Post-surgical Pain
Pain, Chronic
Intercostal Pain
Breast Cancer
Keywords: PPSP
ICBN
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Hamilton Health Sciences Corporation
First posted: 2018-02-05
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: For participants randomized to the ICBN preserving technique, surgeons will perform axillary dissection in which the second ICBN, just inferior to the axillary vein, will be preserved
Primary purpose: PREVENTION

Brief summary: Sacrifice of the intercostobrachial nerve (ICBN) during surgery is associated with development of persistent post-surgical pain (PPSP), which affects up to 60% of breast cancer surgery patients. A large, definitive trial is needed to establish whether nerve preservation techniques are effective in reducing post-surgical pain after breast cancer surgery. If the effect of ICBN preservation is consistent with observational studies, the absolute reduction of rates of persistent pain would be considerable.The primary objective is to determine the effect of ICBN preservation, versus usual care, on the prevalence and intensity of PPSP at one year after breast cancer surgery involving axillary lymph node dissection (ALND). Within the larger INSPIRE pilot, we will also be conducting a biomarker sub-study. The objectives of the biomarker sub-study are: 1) to determine the association between pro-inflammatory cytokine levels and the presence and intensity of persistent pain at 3 weeks, and 3 months post-surgery, and) 2) to determine the effect of study intervention on the change in cytokine levels (pre-operative to post-operative) in participants who consent to participate in the sub-study.

Detailed description: A 2016 systematic review that included 30 observational studies (n= 19,813 patients) found high quality evidence that axillary lymph node dissection (ALND) is associated with a 21% absolute risk increase of PPSP (95% CI = 13% to 29%). In many cases of breast cancer, surgery involves axillary approaches; however, preliminary evidence suggests that preservation of the intercostobrachial nerves (ICBN) may reduce the incidence of PPSP after axillary clearance. A 2014 systematic review found 3 small, single-center randomized controlled trials (RCTs), that enrolled a total of 309 patients, and explored the effect of ICBN preservation versus sacrifice during breast cancer surgery. This review found that division of the ICBN was associated with higher risk of sensory deficits, and that nerve preservation techniques increased the median operating time by 5 minutes. Due to limitations of existing evidence, clinical practice guidelines currently provide no recommendations on whether the ICBN should be preserved during axillary lymph node dissection.A large, definitive trial is needed to establish whether nerve preservation techniques are effective in reducing PPSP after breast cancer surgery involving ALND. If all the apparent effect of axillary dissection is associated with lack of ICBN preservation, the absolute reduction of rates of PPSP would be considerable. Furthermore, nerve sparing requires no specialized equipment, suggesting that scalability will be highly feasible.

In addition, there is substantial evidence that neuro-inflammation as a result of neural damage leads to peripheral and central changes that can be described as peripheral and central sensitization, leading to PPSP. As such, we will be conducting a biomarker sub-study as part of the pilot program. Identification of biomarkers to correlate with the development of neuropathic pain may facilitate identification of individuals at risk for development of PPSP at an early stage. The INSPIRE trial provides an important opportunity to compare patients before and after nerve injury to further explore the association of persistent pain with cytokine biomarkers. The findings will improve our mechanistic understanding of PPSP.

Eligibility criteria: Pilot Study

Inclusion Criteria:

1. Females aged 18 years and older.
2. Known or suspected invasive breast cancer.
3. Planned ALND (not sentinel lymph node biopsy) either alone or with planned mastectomy or breast conserving surgery.
4. The ICBN is preservable (as confirmed in the OR)
5. Cognitive ability and language skills required to complete the outcome measures.
6. Provision of informed consent.

Exclusion Criteria:

1. The patient has chronic pain or a chronic pain syndrome for which they have received daily medication (i.e. opioid, anti-convulsant, anti-spasmodic, anti-depressant, anti-inflammatory) or routine pain intervention (i.e. nerve blocks) during the past 3 months.

   Note: Chronic pain refers to known chronic pain disorder (i.e. post-herpetic neuralgia, complex regional pain syndrome, fibromyalgia, diabetic neuropathy, post-stroke pain, etc.). The diagnosis for a 'chronic pain syndrome' is outlined by the use of pain medications and interventions. The pain medication must be used by the patient to treat pain. For a pain intervention to be considered routine, it must be given in its prescribed frequency during the past three months (e.g. a patient that has been prescribed to receive a nerve block once a month, received three nerve blocks in the past three months).
2. The patient has a prior history of completing ALND on the ipsilateral side.
3. Detectable metastatic disease at the time of initial diagnosis.
4. Planned bilateral ALND.
5. History of shoulder trauma or pathology on the same side as their breast cancer.
6. Preservation of the ICBN is not possible, in the judgement of the attending surgeon (as confirmed in the OR).
7. Anticipated problems with the patient being available for follow-up.
8. Incarceration.
9. The patient is or may be enrolled in a competing trial.
10. Other reason to exclude the patient, as specified.

Biomarker Sub-Study Eligibility:

All eligible patients who consent to participate in the INSPIRE trial will be asked to participate in the biomarker sub-study. Participants who decline to participate in the biomarker sub-study will still be enrolled into the INSPIRE trial. During the pilot phase of the INSPIRE trial, we will confirm our ability to obtain and analyze blood samples from ≥ 90% of INSPIRE participants.

Primary outcomes:
measure: Persistent post-surgical pain (PPSP)
timeFrame: 12 months
measure: Moderate-to-severe PPSP
timeFrame: 12 months
measure: Biomarker Sub-Study: Cytokine Levels and PPSP
timeFrame: 3 weeks, 3 months
measure: Biomarker Sub-Study: Cytokine Levels Pre and Post-Op
timeFrame: 3 weeks
Secondary outcomes:
measure: Operative Time
timeFrame: 12 months
measure: General physical functioning
timeFrame: 12 months
measure: General Mental functioning
timeFrame: 12 months
measure: Upper limb-specific physical functioning
timeFrame: 12 months
measure: Return to Work
timeFrame: 12 months
measure: Adverse Events
timeFrame: 12 months
measure: Pain Interference
timeFrame: 12 months
measure: Use of Prescription Opioids
timeFrame: 12 months
measure: Return to household activities
timeFrame: 12 months
measure: Return to leisure activities
timeFrame: 12 months
measure: Return to pre-surgical functioning
timeFrame: 12 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
Study officials:
affiliation: Hamilton Health Sciences - Juravinski Hospital
name: Susan Dr Reid
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster Michael DeGroote Centre for National Pain Research and Care
name: Jason Busse
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster
name: Sheila Sprague
role: PRINCIPAL_INVESTIGATOR
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