Clinical trial NCT03722927: The Use Of Liposomal Bupivacaine For Pain Control
Official title: The Use of Liposomal Bupivacaine for Pain Control Following Mastectomy and Breast Reconstruction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Breast
Keywords: Bupivacaine
Liposomal Bupivacaine
Mastectomy
Breast Reconstruction
Pain Control
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2018-10-29
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Women of all races and ethnicity who meet the above-described eligibility criteria are eligible to participate in this study. Approximately 5% of study participants to be Hispanic/Latino (N=5), 10% Black or African American (N=10), 1% American Indian/Alaska Native (N=1), and 5% Asian (N=5).
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this research study is to determine how well the local anesthetic, liposomal bupivacaine, controls postoperative pain after mastectomy and breast reconstruction.

Detailed description: Eligible subjects will be identified prior to surgery. On the day of surgery, each patient will be randomized to be in either Local infiltration of bupivacaine OR liposomal bupivacaine. Study will be double blinded to patients and Investigators. Patients assigned to the local infiltration with bupivacaine group will receive a total 60 ml of 0.25% bupivacaine with 30 ml delivered to each breast. Patients assigned to the local infiltration of liposomal bupivacaine will receive a total of 20 ml liposomal bupivacaine (266 mg) with 10 ml of 0.25% bupivacaine and 30 ml of 0.9% sodium chloride. These injections will occur at the end of the mastectomy and prior to the insertion of the tissue expander implant. After this intraoperative injection, patients will not receive any more doses of local anesthetics.

Eligibility criteria: Inclusion Criteria:

* All patients who receive a bilateral mastectomy with immediate sub-pectoral implant based breast reconstruction
* Age ≥ 18 years
* Ability to understand and the willingness to sign an (Institutional Review Board) IRB-approved informed consent document.
* Patients who receive tissue expander placement or direct permanent implant placement will be included in the study.

Exclusion Criteria:

* Patients who receive an autologous tissue reconstruction.
* Patients who receive a unilateral reconstruction.
* Patients who are expected to undergo axillary lymph node dissection
* Patients who have undergone breast irradiation
* Patients who abuse narcotics or have chronic pain (using greater than 40 mg equivalents of oxycodone per day)
* Patients who are wards of the state
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to bupivacaine or liposomal bupivacaine.
* Pregnant women are excluded from this study because pregnancy precluded immediate breast reconstruction in our patient population.
* Patients who weigh less than 50 kg, as there can be dose related toxicities of the bupivacaine dosing used n this study.
* Patients with moderate-severe hepatic or renal impairment because of the increased risk of toxicity.
* Patients receiving bilateral mastectomy with immediate pre-pectoral implant based reconstruction

Primary outcomes:
measure: Mean Visual Analog Scores
timeFrame: 48 hours
Secondary outcomes:
measure: Area Under the Curve Visual Analog Scores (Submuscular Augmentation Mammoplasty)
timeFrame: 48 hours
measure: Number of Morphine Doses Across All Subjects
timeFrame: 1 Month
measure: Length of Stay for Hospitalization
timeFrame: up to 47 Hours
measure: Readmission Rates to the Hospital
timeFrame: Month 2
measure: Frequency of Postoperative Opioid Related Adverse Effects
timeFrame: Postoperatively, 1 week
measure: Pain Intensity With Movement
timeFrame: Up to 2 months
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Christopher M Runyan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lovecchio F, Jordan SW, Lim S, Fine NA, Kim JY. Risk Factors for Complications Differ Between Stages of Tissue-Expander Breast Reconstruction. Ann Plast Surg. 2015 Sep;75(3):275-80. doi: 10.1097/SAP.0000000000000109.
citation: Butz DR, Shenaq DS, Rundell VL, Kepler B, Liederbach E, Thiel J, Pesce C, Murphy GS, Sisco M, Howard MA. Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast Reconstruction. Plast Reconstr Surg Glob Open. 2015 Jun 5;3(5):e391. doi: 10.1097/GOX.0000000000000355. eCollection 2015 May.
citation: Ng SK, Hare RM, Kuang RJ, Smith KM, Brown BJ, Hunter-Smith DJ. Breast Reconstruction Post Mastectomy: Patient Satisfaction and Decision Making. Ann Plast Surg. 2016 Jun;76(6):640-4. doi: 10.1097/SAP.0000000000000242.
citation: Shekhawat L, Busheri L, Dixit S, Patel C, Dhar U, Koppiker C. Patient-Reported Outcomes Following Breast Reconstruction Surgery and Therapeutic Mammoplasty: Prospective Evaluation 1 Year Post-Surgery with BREAST-Q Questionnaire. Indian J Surg Oncol. 2015 Dec;6(4):356-62. doi: 10.1007/s13193-015-0432-x. Epub 2015 Jul 23.
citation: Wallace MS, Wallace AM, Lee J, Dobke MK. Pain after breast surgery: a survey of 282 women. Pain. 1996 Aug;66(2-3):195-205. doi: 10.1016/0304-3959(96)03064-3.
citation: Morrison JE Jr, Jacobs VR. Reduction or elimination of postoperative pain medication after mastectomy through use of a temporarily placed local anesthetic pump vs. control group. Zentralbl Gynakol. 2003 Jan;125(1):17-22. doi: 10.1055/s-2003-40364.
citation: Lee MJ, Daniels SL, Wild JRL, Wilson TR; SYSuRG RAGeS Group. Readmissions after general surgery: a prospective multicenter audit. J Surg Res. 2017 Mar;209:53-59. doi: 10.1016/j.jss.2016.09.020. Epub 2016 Sep 19.
citation: Bonnet F, Marret E. Influence of anaesthetic and analgesic techniques on outcome after surgery. Br J Anaesth. 2005 Jul;95(1):52-8. doi: 10.1093/bja/aei038. Epub 2004 Dec 3.
citation: Strang P. Cancer pain--a provoker of emotional, social and existential distress. Acta Oncol. 1998;37(7-8):641-4. doi: 10.1080/028418698429973.
citation: Zielinski T, Lorenc-Podgorska K, Antoszewski B. Why women who have mastectomy decide not to have breast reconstruction? Pol Przegl Chir. 2015 Feb 3;86(10):451-5. doi: 10.2478/pjs-2014-0081.
citation: American Society of Plastic Surgeons. (2015). Plastic surgery statistics report. Retrived from https://d2wirczt3b6wjm.cloudfront.net/News/Statistics/2015/plastic-surgery-statistics-full-report-2015.pdf
citation: Gassman AA, Yoon AP, Festekjian J, Da Lio AL, Tseng CY, Crisera C. Comparison of immediate postoperative pain in implant-based breast reconstructions. J Plast Reconstr Aesthet Surg. 2016 May;69(5):604-16. doi: 10.1016/j.bjps.2015.12.009. Epub 2016 Jan 7.
citation: Ilfeld BM, Viscusi ER, Hadzic A, Minkowitz HS, Morren MD, Lookabaugh J, Joshi GP. Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. Reg Anesth Pain Med. 2015 Sep-Oct;40(5):572-82. doi: 10.1097/AAP.0000000000000283.
citation: Viscusi ER, Sinatra R, Onel E, Ramamoorthy SL. The safety of liposome bupivacaine, a novel local analgesic formulation. Clin J Pain. 2014 Feb;30(2):102-10. doi: 10.1097/AJP.0b013e318288e1f6.
citation: Khalil KG, Boutrous ML, Irani AD, Miller CC 3rd, Pawelek TR, Estrera AL, Safi HJ. Operative Intercostal Nerve Blocks With Long-Acting Bupivacaine Liposome for Pain Control After Thoracotomy. Ann Thorac Surg. 2015 Dec;100(6):2013-8. doi: 10.1016/j.athoracsur.2015.08.017. Epub 2015 Oct 24.
citation: Fayezizadeh M, Majumder A, Neupane R, Elliott HL, Novitsky YW. Efficacy of transversus abdominis plane block with liposomal bupivacaine during open abdominal wall reconstruction. Am J Surg. 2016 Sep;212(3):399-405. doi: 10.1016/j.amjsurg.2015.12.026. Epub 2016 Apr 12.
citation: Rawlani V, Kryger ZB, Lu L, Fine NA. A local anesthetic pump reduces postoperative pain and narcotic and antiemetic use in breast reconstruction surgery: a randomized controlled trial. Plast Reconstr Surg. 2008 Jul;122(1):39-52. doi: 10.1097/PRS.0b013e3181774349.
citation: Nadeau MH, Saraswat A, Vasko A, Elliott JO, Vasko SD. Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. Aesthet Surg J. 2016 Feb;36(2):NP47-52. doi: 10.1093/asj/sjv149. Epub 2015 Dec 23.
citation: Smoot JD, Bergese SD, Onel E, Williams HT, Hedden W. The efficacy and safety of DepoFoam bupivacaine in patients undergoing bilateral, cosmetic, submuscular augmentation mammaplasty: a randomized, double-blind, active-control study. Aesthet Surg J. 2012 Jan;32(1):69-76. doi: 10.1177/1090820X11430831. Epub 2011 Dec 16.
citation: Coopey SB, Specht MC, Warren L, Smith BL, Winograd JM, Fleischmann K. Use of preoperative paravertebral block decreases length of stay in patients undergoing mastectomy plus immediate reconstruction. Ann Surg Oncol. 2013 Apr;20(4):1282-6. doi: 10.1245/s10434-012-2678-7. Epub 2012 Oct 14.
citation: Andersen KG, Christensen KB, Kehlet H, Bidstup PE. The Effect of Pain on Physical Functioning After Breast Cancer Treatment: Development and Validation of an Assessment Tool. Clin J Pain. 2015 Sep;31(9):794-802. doi: 10.1097/AJP.0000000000000156.
citation: Campbell I, Cavanagh S, Creighton J, French R, Banerjee S, Kerr E, Shirley R. To infiltrate or not? Acute effects of local anaesthetic in breast surgery. ANZ J Surg. 2015 May;85(5):353-7. doi: 10.1111/ans.12541. Epub 2014 Apr 22.
citation: Byager N, Hansen MS, Mathiesen O, Dahl JB. The analgesic effect of wound infiltration with local anaesthetics after breast surgery: a qualitative systematic review. Acta Anaesthesiol Scand. 2014 Apr;58(4):402-10. doi: 10.1111/aas.12287.
citation: Zielinski J, Jaworski R, Smietanska I, Irga N, Wujtewicz M, Jaskiewicz J. A randomized, double-blind, placebo-controlled trial of preemptive analgesia with bupivacaine in patients undergoing mastectomy for carcinoma of the breast. Med Sci Monit. 2011 Oct;17(10):CR589-97. doi: 10.12659/msm.881986.
citation: Tam KW, Chen SY, Huang TW, Lin CC, Su CM, Li CL, Ho YS, Wang WY, Wu CH. Effect of wound infiltration with ropivacaine or bupivacaine analgesia in breast cancer surgery: A meta-analysis of randomized controlled trials. Int J Surg. 2015 Oct;22:79-85. doi: 10.1016/j.ijsu.2015.07.715. Epub 2015 Aug 12.
citation: US Food and Drug Administration. FDA Label Approved on 10/28/2011 for Exparel. US Silver Spring, MD: US Food and Drug Administration. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022496s000lbl.pdf
citation: Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam(R) bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011 Sep;28(9):776-88. doi: 10.1007/s12325-011-0052-y. Epub 2011 Aug 12.
citation: Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011 Dec;54(12):1552-9. doi: 10.1097/DCR.0b013e318232d4c1.
citation: US Food and Drug Administration. Marcaine Bupivcacaine HCl Injection Label. US Silver Spring, MD: US Food and Drug Administration. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018692s015lbl.pdf