Intercostobrachial Nerve Sparing to Reduce Post-Surgical Pain (INSPIRE)
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|ClinicalTrials.gov Identifier: NCT03421522|
Recruitment Status : Recruiting
First Posted : February 5, 2018
Last Update Posted : June 26, 2020
|Condition or disease||Intervention/treatment||Phase|
|Post-surgical Pain Pain, Chronic Intercostal Pain Breast Cancer||Other: ICBN preservation surgery||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|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|
|Masking Description:||Eligible participants will be randomized to one of two treatment groups: 1) ICBN preservation, or 2) usual surgical technique (ICBN sacrifice). Due to the nature of the intervention, it will not be feasible to blind the treating surgeons or the study personnel. The patients, data analysts, and those interpreting the study results will be blinded to treatment allocation.To ensure concealed allocation, eligible patients will be randomized using the randomization function within the REDCap Cloud electronic data capture system. Treatment allocation will be stratified by clinical site to account for systematic differences in surgeons and peri-operative care. To avoid crossover between treatment allocation, randomization will take place in the operating room after the surgeon has confirmed that the participant is a candidate for ICBN preservation.|
|Official Title:||Intercostobrachial Nerve Sparing in Breast Cancer Surgery to Reduce Persistent Post-surgical Pain - an International Randomized Controlled Trial|
|Actual Study Start Date :||October 15, 2019|
|Estimated Primary Completion Date :||December 1, 2020|
|Estimated Study Completion Date :||December 1, 2020|
Experimental: Intervention - ICBN preservation
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.
Other: ICBN preservation surgery
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. Surgeons will be asked to indicate whether the ICBN nerve was fully preserved, partially preserved, or sacrificed.
All study participants will receive anesthetic management at the discretion of the attending physician, which will be documented.
No Intervention: Control - Usual Care
For participants allocated to the usual surgical care arm, attending surgeons will perform a standard Level 1 and 2 axillary node dissection (sacrifice of the ICBN), either alone or with mastectomy or breast conserving surgery.
- Persistent post-surgical pain (PPSP) [ Time Frame: 12 months ]
Post-surgery as defined by the World Health Organization (WHO).
The WHO's definition requires 4 criteria for the diagnosis of PPSP:
- Pain that began after surgery or a tissue trauma is experienced;
- The pain is in an area of preceding surgery or tissue trauma,
- The pain has persisted for at least three months after surgery, and
- The pain is not better explained by an infection, malignancy, a pre-existing pain condition or any other alternative cause.
- Moderate-to-severe PPSP [ Time Frame: 12 months ]
We will establish the severity of PPSP with an item from the Brief Pain Inventory Short Form (BPI-SF), which asks patients to report their 'average' pain intensity rating in the past 24 hrs, on a scale of 0 (no pain) to 10 (maximum pain).
As per the BPI-SF scoring system, we will define moderate-to-severe pain as scores of ≥4 out of 10.
- Biomarker Sub-Study: Cytokine Levels and PPSP [ Time Frame: 3 weeks, 3 months ]We will determine the correlation between pro-inflammatory cytokine levels and the presence and intensity of persistent pain at 3 weeks, and 3 months post-surgery
- Biomarker Sub-Study: Cytokine Levels Pre and Post-Op [ Time Frame: 3 weeks ]We will determine the effect of the study intervention on the change in cytokine levels (pre-operative to post-operative) in participants who consent to participate in the sub-study.
- Operative Time [ Time Frame: 12 months ]Operative time will be measured from the time of the first incision until the time of closure of the incision.
- General physical functioning [ Time Frame: 12 months ]
Short Form-36 Health Assessment Survey (SF-36) Physical Component Summary score.
The range of possible scores goes from 0 (worst possible physical functioning) to 100 (best possible physical functioning)
- General Mental functioning [ Time Frame: 12 months ]
Short Form-36 Health Assessment Survey (SF-36) Mental Component Summary score.
The range of possible scores goes from 0 (worst possible mental functioning) to 100 (best possible mental functioning)
- Upper limb-specific physical functioning [ Time Frame: 12 months ]
The Quick-Disability Arm Shoulder Hand Survey (Quick-DASH).
An 11-item scale that measures physical function in people with any or multiple musculoskeletal disorders of the upper limb.
The range of scores goes from 0 (worst possible functioning) to 100 (best possible functioning).
- Return to Work [ Time Frame: 12 months ]We will document when participants, who were employed before their surgery, return to work.
- Adverse Events [ Time Frame: 12 months ]All adverse events will be documented on the study specific case report forms. An independent medical monitor will also review each adverse event to determine its relatedness to the surgical treatment.
- Pain Interference [ Time Frame: 12 months ]
Item PAININ18 of the PROMIS will be used to determine the proportion of patients who report somewhat-to-very much pain interference over 12 months post-surgery.
This item is scored from 0 (not at all) to 4 (very much), and we will use a cut-off value of 2 (somewhat) or higher to define an event.
- Use of Prescription Opioids [ Time Frame: 12 months ]We will capture the proportion of patients who are prescribed an opioid at 3, 6, 9 and 12-months post-surgery, including the type and dose.
- Return to household activities [ Time Frame: 12 months ]We will document when participants return to their normal household activities.
- Return to leisure activities [ Time Frame: 12 months ]We will document when participants return to their normal leisure activities.
- Return to pre-surgical functioning [ Time Frame: 12 months ]We will document when participants achieve 80% of their pre-surgery function, as measured on a percentage scale of 0% (no function) to 100% (full pre-surgical function).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03421522
|Contact: Toni Tidy||905-525-9140 ext firstname.lastname@example.org|
|Contact: Gina Del Fabbroemail@example.com|
|Hamilton, Ontario, Canada, L8V 1C3|
|Contact: Susan Reid, MD 905-521-2100 ext 73188 firstname.lastname@example.org|
|Principal Investigator:||Susan Dr Reid||Hamilton Health Sciences - Juravinski Hospital|
|Principal Investigator:||Jason Busse||McMaster Michael DeGroote Centre for National Pain Research and Care|
|Principal Investigator:||Sheila Sprague||McMaster|