Intercostobrachial Nerve Sparing in Breast Cancer Surgery to Reduce Persistent Post-surgical Pain - an International Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Moderate-to-severe PPSP
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females aged 18 years and older.
- •Known or suspected invasive breast cancer.
- •Planned ALND (not sentinel lymph node biopsy) either alone or with planned mastectomy or breast conserving surgery.
- •The ICBN is preservable (as confirmed in the OR)
- •Cognitive ability and language skills required to complete the outcome measures.
- •Provision of informed consent.
排除标准
- •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).
- •The patient has a prior history of completing ALND on the ipsilateral side.
- •Detectable metastatic disease at the time of initial diagnosis.
- •Planned bilateral ALND.
- •History of shoulder trauma or pathology on the same side as their breast cancer.
- •Preservation of the ICBN is not possible, in the judgement of the attending surgeon (as confirmed in the OR).
- •Anticipated problems with the patient being available for follow-up.
- •Incarceration.
- •The patient is or may be enrolled in a competing trial.
- •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.
结局指标
主要结局
Moderate-to-severe PPSP
时间窗: 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.
Persistent post-surgical pain (PPSP)
时间窗: 12 months
Post-surgery as defined by the World Health Organization (WHO). The WHO's definition requires 4 criteria for the diagnosis of PPSP: 1. Pain that began after surgery or a tissue trauma is experienced; 2. The pain is in an area of preceding surgery or tissue trauma, 3. The pain has persisted for at least three months after surgery, and 4. The pain is not better explained by an infection, malignancy, a pre-existing pain condition or any other alternative cause.
Biomarker Sub-Study: Cytokine Levels and PPSP
时间窗: 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
时间窗: 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.
次要结局
- General physical functioning(12 months)
- Return to Work(12 months)
- Pain Interference(12 months)
- Return to leisure activities(12 months)
- Return to pre-surgical functioning(12 months)
- General Mental functioning(12 months)
- Adverse Events(12 months)
- Use of Prescription Opioids(12 months)
- Upper limb-specific physical functioning(12 months)
- Return to household activities(12 months)
- Operative Time(12 months)