Clinical trial NCT05763667: Pilot: Intraoperative TAP Block and Post-operative Pain Control for Minimally Invasive Hysterectomy for Endometrial Cancer
Official title: A Randomized, Controlled, Observer-blinded Pilot Trial of Laparoscopic Large Volume, Multisite Transversus Abdominal Plane (TAP) Block With Liposomal Bupivacaine in Patients Undergoing Minimally Invasive Hysterectomy for Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post Operative Pain
Gynecologic Cancer
Keywords: hysterectomy
minimally invasive surgery
TAP block
endometrial cancer
endometrial intraepithelial neoplasia
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
First posted: 2023-03-10
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Potential subjects will be identified in the GYN specialty clinics at Tufts Medical Center and approached for possible study participation. Eligibility criteria will be assessed by the PI or co-I. Eligible subjects who wish to participate in the study will be consented for the study by the PI or co-I. Informed consent for the study may be obtained up to the day of the surgery, prior to anesthesia induction. The following demographics will be collected from the medical record and de-identified: age, race, ethnicity, height, weight, ASA class.

On the day of surgery, the subject will be randomized using a random number generator to one of 3 groups:

1. No TAP block
2. TAP block with liposomal and plain bupivacaine: 20 mL liposomal bupivacaine, 30 mL 0.25% bupivacaine, 150 mL normal saline (200 mL total)
3. TAP block with plain bupivacaine alone: 60 mL of 0.25% bupivacaine, 140 mL of normal saline (200 mL total)
Primary purpose: TREATMENT

Brief summary: Modern postoperative pain management aims to optimizing pain relief while minimizing opiate usage. While opiates are effective for pain relief, they result in common adverse effects such as nausea, constipation, and urinary retention, and most importantly present a long-term risk of abuse and dependency. Commonly used approaches include non-opiate pain medications such as acetominophen and non-steroidal anti-inflammatory agents, as well as regional nerve blocks such as epidurals.

The transversus abdominis plane (TAP) block is a fascial plane block performed by injecting local anesthetic into the plane superficial to the transversus abdominis muscle where the anterior rami of the spinal nerves course to provide sensory innervation to the abdominal wall. The injections are generally placed either subcostally or at the midaxillary line bilaterally. The TAP block has been shown to be effective in reducing pain scores and opiate usage in some randomized studies but not others in patients undergoing various abdominal surgeries. There is great variation in method of administration, sites injected, and local anesthetics used, which may in part account for the heterogeneity of trial results.

Detailed description: The investigators believe that the disappointing results thus far with TAP blocks in minimally invasive hysterectomy may relate to several factors. A combination of short and long-acting anesthetic agents may provide the optimal analgesic effect. Large volumes of injection may promote spread of the anesthetics for better coverage, especially as long-acting agents are known to diffuse minimally. Lastly, multiple injections may provide better coverage of the nerves that innervate the abdominal wall.

The investigators also believe that laparoscopic TAP blocks, administered by the surgeon, have advantages over the more commonly used ultrasound-guided approach typically performed by anesthesiologists. The laparoscopic approach is quick, on the order of a few minutes, whereas the ultrasound approach can be time-consuming. There is also less risk of visceral injury since the injection is performed under direct laparoscopic view. There are now 2 randomized studies suggesting that the laparoscopic approach is equivalent to the ultrasound approach.

An additional potential reason why most studies have been negative is that patients undergoing minimally invasive hysterectomy do not generally experience severe pain, making it more difficult to demonstrate pain reduction with any given intervention. However, the studies to date do indicate that these patients experience moderate pain and do use opiates. An intervention that markedly reduces or even eliminates opiate use would be of potential benefit.

The investigators have used a TAP block technique that is performed intraoperatively by the surgeon under direct laparoscopic view. The investigators use a mixture of plain and liposomal bupivacaine injected at multiple sites and in large volume to distribute the drugs widely, potentially resulting in longer and improved efficacy. This method has not been previously studied in a randomized trial. The investigators propose to demonstrate that this technique markedly decreases opiate usage and pain scores in patients undergoing minimally invasive hysterectomy.

Eligibility criteria: Inclusion Criteria:

1. Age 18-80
2. Patients undergoing laparoscopic or robotic hysterectomy; may include other procedures (e.g. lymph node removal)
3. Endometrial cancer or endometrial intraepithelial neoplasia
4. Able to consent to study

Exclusion Criteria:

1. Known clinically significant allergy to bupivacaine or liposomal bupivacaine
2. ASA IV or V
3. Emergency surgery
4. Current chronic opiate use
5. Current pregnancy or breastfeeding
6. Severe hepatic or renal impairment
7. Hysterectomy is not for endometrial cancer or endometrial intraepithelial neoplasia

Primary outcomes:
measure: Reduced opiate use in both TAP block arms.
timeFrame: 7 days
Secondary outcomes:
measure: Increase in opiate-free participants by day 7
timeFrame: 7 days
measure: Reduction in post-operative resting pain scores
timeFrame: 7 days
measure: Improvement in patient satisfaction regarding pain control
timeFrame: 7 days
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 7 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Young B Kim, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ohel G, Kisselevitz R, Margalioth EJ, Schenker JG. Ascorbate-dependent lipid peroxidation in the human placenta and fetal membranes. Gynecol Obstet Invest. 1985;19(2):73-7. doi: 10.1159/000299011.
citation: Cserhati G, Szilagyi J, Pongracz S. [Yersinia pseudotuberculosis infection]. Orv Hetil. 1982 Jun 6;123(23):1431-2. No abstract available. Hungarian.
citation: Babazade R, Saasouh W, Naylor AJ, Makarova N, Udeh CI, Turan A, Udeh BL. The cost-effectiveness of epidural, patient-controlled intravenous opioid analgesia, or transversus abdominis plane infiltration with liposomal bupivacaine for postoperative pain management. J Clin Anesth. 2019 Mar;53:56-63. doi: 10.1016/j.jclinane.2018.10.003. Epub 2018 Oct 13.
citation: Rafi AN. Abdominal field block: a new approach via the lumbar triangle. Anaesthesia. 2001 Oct;56(10):1024-6. doi: 10.1046/j.1365-2044.2001.02279-40.x. No abstract available.
citation: Hebbard P, Fujiwara Y, Shibata Y, Royse C. Ultrasound-guided transversus abdominis plane (TAP) block. Anaesth Intensive Care. 2007 Aug;35(4):616-7. No abstract available.
citation: Seitz F. Science, the universities, and society. Am Sci. 1968 Autumn;56(3):288-97. No abstract available.
citation: Baeriswyl M, Kirkham KR, Kern C, Albrecht E. The Analgesic Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block in Adult Patients: A Meta-Analysis. Anesth Analg. 2015 Dec;121(6):1640-54. doi: 10.1213/ANE.0000000000000967.
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: Hamilton TW, Athanassoglou V, Trivella M, Strickland LH, Mellon S, Murray D, Pandit HG. Liposomal bupivacaine peripheral nerve block for the management of postoperative pain. Cochrane Database Syst Rev. 2016 Aug 25;2016(8):CD011476. doi: 10.1002/14651858.CD011476.pub2.
citation: Ji YD, Harris JA, Gibson LE, McKinley SK, Phitayakorn R. The Efficacy of Liposomal Bupivacaine for Opioid and Pain Reduction: A Systematic Review of Randomized Clinical Trials. J Surg Res. 2021 Aug;264:510-533. doi: 10.1016/j.jss.2021.02.024. Epub 2021 Apr 13.
citation: Wong KA, Cabrera AG, Argiroff AL, Pechman DM, Parides MK, Vazzana JT, Moran-Atkin EM, Choi JJ, Camacho DR. Transversus abdominis plane block with liposomal bupivacaine and its effect on opiate use after weight loss surgery: a randomized controlled trial. Surg Obes Relat Dis. 2020 Jul;16(7):886-893. doi: 10.1016/j.soard.2020.03.031. Epub 2020 Apr 10.
citation: Truong A, Fleshner PR, Mirocha JM, Tran HP, Shane R, Zaghiyan KN. A Prospective Randomized Trial of Surgeon-Administered Intraoperative Transversus Abdominis Plane Block With Bupivacaine Against Liposomal Bupivacaine: The TINGLE Trial. Dis Colon Rectum. 2021 Jul 1;64(7):888-898. doi: 10.1097/DCR.0000000000002008.
citation: Okamoto Y, Ota K. [Changes in calcium regulating hormone in osteoporosis]. Nihon Rinsho. 1994 Sep;52(9):2295-300. Japanese.
citation: Fidkowski CW, Choksi N, Alsaden MR. A randomized-controlled trial comparing liposomal bupivacaine, plain bupivacaine, and the mixture of liposomal bupivacaine and plain bupivacaine in transversus abdominus plane block for postoperative analgesia for open abdominal hysterectomies. Can J Anaesth. 2021 Jun;68(6):773-781. doi: 10.1007/s12630-020-01911-1. Epub 2021 Jan 11.
citation: Hutchins J, Delaney D, Vogel RI, Ghebre RG, Downs LS Jr, Carson L, Mullany S, Teoh D, Geller MA. Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: A prospective randomized controlled study. Gynecol Oncol. 2015 Sep;138(3):609-13. doi: 10.1016/j.ygyno.2015.06.008. Epub 2015 Jun 6.
citation: Ghisi D, Fanelli A, Vianello F, Gardini M, Mensi G, La Colla L, Danelli G. Transversus Abdominis Plane Block for Postoperative Analgesia in Patients Undergoing Total Laparoscopic Hysterectomy: A Randomized, Controlled, Observer-Blinded Trial. Anesth Analg. 2016 Aug;123(2):488-92. doi: 10.1213/ANE.0000000000001267.
citation: Kane SM, Garcia-Tomas V, Alejandro-Rodriguez M, Astley B, Pollard RR. Randomized trial of transversus abdominis plane block at total laparoscopic hysterectomy: effect of regional analgesia on quality of recovery. Am J Obstet Gynecol. 2012 Nov;207(5):419.e1-5. doi: 10.1016/j.ajog.2012.06.052. Epub 2012 Jun 29.
citation: Bringer J, Klawatsch D, Jaffiol C, Orsetti A, Robin M, Mirouze J. [Comparison of various treatments for tumoral acromegaly. Study of initial prognostic factors]. Ann Endocrinol (Paris). 1983 Mar-Apr;44(2):107-14. No abstract available. French.
citation: Calle GA, Lopez CC, Sanchez E, De Los Rios JF, Vasquez EM, Serna E, Arango AM, Castaneda JD, Vasquez RA, Gonzalez A, Escobar A, Almanza LA. Transversus abdominis plane block after ambulatory total laparoscopic hysterectomy: randomized controlled trial. Acta Obstet Gynecol Scand. 2014 Apr;93(4):345-50. doi: 10.1111/aogs.12351.
citation: Hotujec BT, Spencer RJ, Donnelly MJ, Bruggink SM, Rose SL, Al-Niaimi A, Chappell R, Stewart SL, Kushner DM. Transversus abdominis plane block in robotic gynecologic oncology: a randomized, placebo-controlled trial. Gynecol Oncol. 2015 Mar;136(3):460-5. doi: 10.1016/j.ygyno.2014.11.013. Epub 2014 Nov 20.
citation: Torup H, Bogeskov M, Hansen EG, Palle C, Rosenberg J, Mitchell AU, Petersen PL, Mathiesen O, Dahl JB, Moller AM. Transversus abdominis plane (TAP) block after robot-assisted laparoscopic hysterectomy: a randomised clinical trial. Acta Anaesthesiol Scand. 2015 Aug;59(7):928-35. doi: 10.1111/aas.12516. Epub 2015 May 31.
citation: Bharti N, Kumar P, Bala I, Gupta V. The efficacy of a novel approach to transversus abdominis plane block for postoperative analgesia after colorectal surgery. Anesth Analg. 2011 Jun;112(6):1504-8. doi: 10.1213/ANE.0b013e3182159bf8. Epub 2011 Apr 5.
citation: Chetwood A, Agrawal S, Hrouda D, Doyle P. Laparoscopic assisted transversus abdominis plane block: a novel insertion technique during laparoscopic nephrectomy. Anaesthesia. 2011 Apr;66(4):317-8. doi: 10.1111/j.1365-2044.2011.06664.x. No abstract available.
citation: Owen DJ, Harrod I, Ford J, Luckas M, Gudimetla V. The surgical transversus abdominis plane block--a novel approach for performing an established technique. BJOG. 2011 Jan;118(1):24-7. doi: 10.1111/j.1471-0528.2010.02779.x. Epub 2010 Nov 18.
citation: Park SY, Park JS, Choi GS, Kim HJ, Moon S, Yeo J. Comparison of Analgesic Efficacy of Laparoscope-Assisted and Ultrasound-Guided Transversus Abdominis Plane Block after Laparoscopic Colorectal Operation: A Randomized, Single-Blind, Non-Inferiority Trial. J Am Coll Surg. 2017 Sep;225(3):403-410. doi: 10.1016/j.jamcollsurg.2017.05.017. Epub 2017 Jun 10.
citation: Wong DJ, Curran T, Poylin VY, Cataldo TE. Surgeon-delivered laparoscopic transversus abdominis plane blocks are non-inferior to anesthesia-delivered ultrasound-guided transversus abdominis plane blocks: a blinded, randomized non-inferiority trial. Surg Endosc. 2020 Jul;34(7):3011-3019. doi: 10.1007/s00464-019-07097-y. Epub 2019 Sep 4.
citation: Einarsson JI, Sun J, Orav J, Young AE. Local analgesia in laparoscopy: a randomized trial. Obstet Gynecol. 2004 Dec;104(6):1335-9. doi: 10.1097/01.AOG.0000146283.90934.fd.
citation: Tam T, Harkins G, Wegrzyniak L, Ehrgood S, Kunselman A, Davies M. Infiltration of bupivacaine local anesthetic to trocar insertion sites after laparoscopy: a randomized, double-blind, stratified, and controlled trial. J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):1015-21. doi: 10.1016/j.jmig.2014.04.013. Epub 2014 May 2.
citation: Hortu I, Turkay U, Terzi H, Kale A, Yilmaz M, Balci C, Aydin U, Lagana AS. Impact of bupivacaine injection to trocar sites on postoperative pain following laparoscopic hysterectomy: Results from a prospective, multicentre, double-blind randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2020 Sep;252:317-322. doi: 10.1016/j.ejogrb.2020.07.007. Epub 2020 Jul 7.
citation: Barron KI, Lamvu GM, Schmidt RC, Fisk M, Blanton E, Patanwala I. Wound Infiltration With Extended-Release Versus Short-Acting Bupivacaine Before Laparoscopic Hysterectomy: A Randomized Controlled Trial. J Minim Invasive Gynecol. 2017 Feb;24(2):286-292. doi: 10.1016/j.jmig.2016.11.002. Epub 2016 Nov 14.