Intercostobrachial Nerve Sparing to Reduce Post-Surgical Pain

NCT ID: NCT03421522

Last Updated: 2020-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-15

Study Completion Date

2020-12-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Post-surgical Pain Pain, Chronic Intercostal Pain Breast Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

ICBN preservation surgery

Intervention Type OTHER

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.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Hamilton Health Sciences Corporation

OTHER

Sponsor Role collaborator

McMaster University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Susan Dr Reid

Role: PRINCIPAL_INVESTIGATOR

Hamilton Health Sciences - Juravinski Hospital

Jason Busse

Role: PRINCIPAL_INVESTIGATOR

McMaster Michael DeGroote Centre for National Pain Research and Care

Sheila Sprague

Role: PRINCIPAL_INVESTIGATOR

McMaster

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Juravinski Hospital

Hamilton, Ontario, Canada

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Canada

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Toni Tidy

Role: CONTACT

905-525-9140 ext. 21737

Gina Del Fabbro

Role: CONTACT

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Susan Reid, MD

Role: primary

905-521-2100 ext. 73188

References

Explore related publications, articles, or registry entries linked to this study.

Andersen KG, Kehlet H. Persistent pain after breast cancer treatment: a critical review of risk factors and strategies for prevention. J Pain. 2011 Jul;12(7):725-46. doi: 10.1016/j.jpain.2010.12.005. Epub 2011 Mar 24.

Reference Type BACKGROUND
PMID: 21435953 (View on PubMed)

Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization Study in Primary Care. JAMA. 1998 Jul 8;280(2):147-51. doi: 10.1001/jama.280.2.147.

Reference Type BACKGROUND
PMID: 9669787 (View on PubMed)

Wang L, Guyatt GH, Kennedy SA, Romerosa B, Kwon HY, Kaushal A, Chang Y, Craigie S, de Almeida CPB, Couban RJ, Parascandalo SR, Izhar Z, Reid S, Khan JS, McGillion M, Busse JW. Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies. CMAJ. 2016 Oct 4;188(14):E352-E361. doi: 10.1503/cmaj.151276. Epub 2016 Jul 11.

Reference Type BACKGROUND
PMID: 27402075 (View on PubMed)

Warrier S, Hwang S, Koh CE, Shepherd H, Mak C, Carmalt H, Solomon M. Preservation or division of the intercostobrachial nerve in axillary dissection for breast cancer: meta-analysis of randomised controlled trials. Breast. 2014 Aug;23(4):310-6. doi: 10.1016/j.breast.2014.01.014. Epub 2014 Feb 24.

Reference Type BACKGROUND
PMID: 24582033 (View on PubMed)

Gherghe M, Bordea C, Blidaru A. Sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND) in the current surgical treatment of early stage breast cancer. J Med Life. 2015 Apr-Jun;8(2):176-80.

Reference Type BACKGROUND
PMID: 25866575 (View on PubMed)

Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. A classification of chronic pain for ICD-11. Pain. 2015 Jun;156(6):1003-1007. doi: 10.1097/j.pain.0000000000000160. No abstract available.

Reference Type BACKGROUND
PMID: 25844555 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15042521 (View on PubMed)

Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003.

Reference Type BACKGROUND
PMID: 8628042 (View on PubMed)

Angst F, Aeschlimann A, Stucki G. Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities. Arthritis Rheum. 2001 Aug;45(4):384-91. doi: 10.1002/1529-0131(200108)45:43.0.CO;2-0.

Reference Type BACKGROUND
PMID: 11501727 (View on PubMed)

Jenkinson C, Stewart-Brown S, Petersen S, Paice C. Assessment of the SF-36 version 2 in the United Kingdom. J Epidemiol Community Health. 1999 Jan;53(1):46-50. doi: 10.1136/jech.53.1.46.

Reference Type BACKGROUND
PMID: 10326053 (View on PubMed)

Busse JW, Bhandari M, Guyatt GH, Heels-Ansdell D, Mandel S, Sanders D, Schemitsch E, Swiontkowski M, Tornetta P 3rd, Wai E, Walter SD; SPRINT Investigators. Use of both Short Musculoskeletal Function Assessment questionnaire and Short Form-36 among tibial-fracture patients was redundant. J Clin Epidemiol. 2009 Nov;62(11):1210-7. doi: 10.1016/j.jclinepi.2009.01.014. Epub 2009 Apr 11.

Reference Type BACKGROUND
PMID: 19364637 (View on PubMed)

Mintken PE, Glynn P, Cleland JA. Psychometric properties of the shortened disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH) and Numeric Pain Rating Scale in patients with shoulder pain. J Shoulder Elbow Surg. 2009 Nov-Dec;18(6):920-6. doi: 10.1016/j.jse.2008.12.015. Epub 2009 Mar 17.

Reference Type BACKGROUND
PMID: 19297202 (View on PubMed)

Trudel JG, Rivard M, Dobkin PL, Leclerc JM, Robaey P. Psychometric properties of the Health Utilities Index Mark 2 system in paediatric oncology patients. Qual Life Res. 1998 Jul;7(5):421-32. doi: 10.1023/a:1008857920624.

Reference Type BACKGROUND
PMID: 9691722 (View on PubMed)

Brodke DJ, Saltzman CL, Brodke DS. PROMIS for Orthopaedic Outcomes Measurement. J Am Acad Orthop Surg. 2016 Nov;24(11):744-749. doi: 10.5435/JAAOS-D-15-00404.

Reference Type BACKGROUND
PMID: 27661391 (View on PubMed)

Fries JF, Bruce B, Cella D. The promise of PROMIS: using item response theory to improve assessment of patient-reported outcomes. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S53-7.

Reference Type BACKGROUND
PMID: 16273785 (View on PubMed)

Khan JS, Devereaux PJ, LeManach Y, Busse JW. Patient coping and expectations about recovery predict the development of chronic post-surgical pain after traumatic tibial fracture repair. Br J Anaesth. 2016 Sep;117(3):365-70. doi: 10.1093/bja/aew225.

Reference Type BACKGROUND
PMID: 27543531 (View on PubMed)

Reininga IH, Brouwer S, Dijkstra A, Busse JW, Ebrahim S, Wendt KW, El Moumni M. Measuring illness beliefs in patients with lower extremity injuries: reliability and validity of the Dutch version of the Somatic Pre-Occupation and Coping questionnaire (SPOC-NL). Injury. 2015 Feb;46(2):308-14. doi: 10.1016/j.injury.2014.08.042. Epub 2014 Sep 16.

Reference Type BACKGROUND
PMID: 25441575 (View on PubMed)

Busse JW, Bhandari M, Guyatt GH, Heels-Ansdell D, Kulkarni AV, Mandel S, Sanders D, Schemitsch E, Swiontkowski M, Tornetta P 3rd, Wai E, Walter SD; SPRINT Investigators & the Medically Unexplained Syndromes Study Group. Development and validation of an instrument to predict functional recovery in tibial fracture patients: the Somatic Pre-Occupation and Coping (SPOC) questionnaire. J Orthop Trauma. 2012 Jun;26(6):370-8. doi: 10.1097/BOT.0b013e31822421e2.

Reference Type BACKGROUND
PMID: 22011635 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9782034 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9630850 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12968959 (View on PubMed)

Sprague S, Leece P, Bhandari M, Tornetta P 3rd, Schemitsch E, Swiontkowski MF; S.P.R.I.N.T. Investigators. Limiting loss to follow-up in a multicenter randomized trial in orthopedic surgery. Control Clin Trials. 2003 Dec;24(6):719-25. doi: 10.1016/j.cct.2003.08.012.

Reference Type BACKGROUND
PMID: 14662277 (View on PubMed)

Madden K, Scott T, McKay P, Petrisor BA, Jeray KJ, Tanner SL, Bhandari M, Sprague S. Predicting and Preventing Loss to Follow-up of Adult Trauma Patients in Randomized Controlled Trials: An Example from the FLOW Trial. J Bone Joint Surg Am. 2017 Jul 5;99(13):1086-1092. doi: 10.2106/JBJS.16.00900.

Reference Type BACKGROUND
PMID: 28678121 (View on PubMed)

Zhang Y, Alyass A, Vanniyasingam T, Sadeghirad B, Florez ID, Pichika SC, Kennedy SA, Abdulkarimova U, Zhang Y, Iljon T, Morgano GP, Colunga Lozano LE, Aloweni FAB, Lopes LC, Yepes-Nunez JJ, Fei Y, Wang L, Kahale LA, Meyre D, Akl EA, Thabane L, Guyatt GH. A systematic survey of the methods literature on the reporting quality and optimal methods of handling participants with missing outcome data for continuous outcomes in randomized controlled trials. J Clin Epidemiol. 2017 Aug;88:67-80. doi: 10.1016/j.jclinepi.2017.05.016. Epub 2017 Jun 1.

Reference Type BACKGROUND
PMID: 28579378 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.cancer.ca

Canadian Cancer Statistics

http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-042725.pdf

Breast cancer facts and figures 2013-2014. Atlanta: American Cancer Society; 2013

http://dx.doi.org/10.1016/j.jpain.2013.01.487

Visnjevac OM, B. Postmastectomy pain syndrome: an unrecognized annual billion dollar national financial burden. J Pain 2013;14

https://www.ncbi.nlm.nih.gov/pubmed/25307709

K. M. Intercostobrachial syndrome after nerve-sparing axillary lymph node dissection. Eur J Cancer. 2014;50:S127.

http://www.bmj.com/content/355/bmj.i5351

Busse JW, Bhandari M, Einhorn TA, Schemitsch E, Heckman JD, Tornetta P, 3rd, et al. Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial. Bmj. 2016;355:i5351.

http://janelhanmer.pitt.edu/ProPr.html

Hamner J, Dewitt B. The Development of a Preference-based Scoring System for PROMIS (PROPr): A Technical Report v 1.1. \[Internet\] 2017;available from: http://janelhanmer.pitt.edu/documents/technicalreportv1.1.pdf (accessed August 29, 2017).

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

INSPIRE-001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.