Clinical trial NCT04777591
Conditions: Postoperative Pain Breast Reconstruction
Keywords: TAP block Regional block ERAS liposomal bupivacaine free flap
Sponsor: University of Virginia
Start date: 2021-03-01; Completion date: 2022-12-28
Enrollment: 117 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Transversus Abdominis Plane (TAP) block is a useful tool in pain management after abdominal surgery. It is a regional nerve block that targets T6-L1 thoracolumbar nerves running in the plane between internal oblique and transversus abdominis muscle. It is shown to help with post-operative pain management, reducing pain scores and narcotic pain medication use, as well as promoting earlier return to activity and recovery. TAP block became a very popular, safe, and effective therapeutic adjunct for many different abdominal surgeries ranging from obstetric procedures to general surgery procedures like colorectal surgery. Furthermore, it is used in plastic surgery procedures such as Deep Inferior Epigastric Perforator (DIEP) free flap or Transverse Rectus Abdominis Myocutaneous (TRAM) flap, as they involve extensive amount of abdominal soft tissue incision. Previous studies have shown that TAP block in these procedures significantly reduce post-op pain and narcotic pain medication use. More recently, Exparel (liposomal bupivacaine) has risen to spotlight for providing a longer, sustained local anesthesia. Various surgical disciplines have adopted this agent as part of their pain management protocol. However, there are no literatures that describe the effect of TAP block using Exparel for breast free flap population. The study hypothesize that delivering TAP block with Exparel (vs. plain bupivacaine) will provide longer regional blocking effect, hence aiding in pain control and recovery postoperatively. The investigators will be analyzing postop narcotic pain medication requirement and pain scores to look into this question.

Detailed description:

Arms: arm 1: Receives plain bupivacaine TAP block as part of multi-modal pain control intraoperatively arm 2: Receives plain bupivacaine + liposomal bupivacaine TAP block as part of multi-modal pain control intraoperatively
Interventions: intervention 1: Liposomal bupivacaine TAP block intervention 2: Bupivacain
Intervention descriptions: intervention 1: Group will receive Liposomal bupivacaine TAP block (mixed with plain bupivacaine) intraoperatively during free flap breast reconstruction as part of the multimodal pain control. intervention 2: Group will receive plain bupivacaine TAP block intraoperatively during free flap breast reconstruction as part of the multimodal pain control.

Protocol documents:
Prot_SAP_000.pdf: 
HSR#210033: Effectiveness of Exparel TAP block in breast free flap reconstruction 
 
Version Date: 02/27/21 
Page Number: 1 of 6 
 
PROTOCOL 
 
Background 
1. Provide the scientific background, rationale and relevance of this project.   
Answer/Response:  
Transversus Abdominis Plane (TAP) block is a useful tool in pain management after 
abdominal surgery. It is a regional nerve block that targets T6-L1 thoracolumbar 
nerves running in the plane between internal oblique and transversus abdominis 
muscle. It is shown to help with post-operative pain management, reducing pain 
scores and narcotic pain medication use, as well as promoting earlier return to activity 
and recovery.1,2 TAP block became a very popular, safe, and effective therapeutic 
adjunct for many different abdominal surgeries ranging from obstetric procedures to 
general surgery procedures like colorectal surgery.3,4 Furthermore, it is used in plastic 
surgery procedures such as Deep Inferior Epigastric Perforator (DIEP) free flap or 
Transverse Rectus Abdominis Myocutaneous (TRAM) flap, as they involve extensive 
amount of abdominal soft tissue incision. Previous studies have shown that TAP 
block in these procedures significantly reduce post-op pain and narcotic pain 
medication use.5,6 More recently, Exparel (liposomal bupivacaine) has risen to spotlight for 
providing a longer, sustained local anesthesia. Various surgical disciplines have adopted this 
agent as part of their pain management protocol. However, there are no literatures that 
describe the effect of TAP block using Exparel for breast free flap population. We hypothesize 
that delivering TAP block with Exparel (vs. plain bupivacaine) will provide longer regional 
blocking effect, hence aiding in pain control and recovery postoperatively.  
 
Objectives/Hypothesis  
Answer/Response: 
 We hypothesize that liposomal bupivacaine (Exparel) TAP block will provide longer pain 
control compared to plain bupivacaine TAP block in abdomen-based free flap breast. 
 Primary outcome = post-op pain scores during hospitalization, post-op narcotic pain 
medication use during hospitalization, post-op narcotic pain medication use after 
discharge (within 30 days of discharge)  
 Secondary outcome = Length of stay, Post-op nausea and vomiting (PONV) 
Study Design: Biomedical 
1.  Will controls be used? 
Answer/Response: Yes 
 
►IF YES, explain the kind of controls to be used. 
Answer/Response: Usual care, TAP block with plain bupivacaine  


HSR#210033: Effectiveness of Exparel TAP block in breast free flap reconstruction 
 
Version Date: 02/27/21 
Page Number: 2 of 6 
 
2. What is the study design?  
Answer/Response: Randomized, single-blind control study  
 
3. 
Does the study involve a placebo? 
Answer/Response: No 
Human Participants 
Ages: _18 and older___ 
Sex: 
__Female__ 
Race: ___Any_ 
 
Subjects- see below 
 
1.  Provide target # of subjects (at all sites) needed to complete protocol. 
Answer/Response:  
100 participants  
 
2.  Describe expected rate of screen failure/ dropouts/withdrawals from all sites.   
Answer/Response:  
Minimal.  
Once the patient consents to the study, it is unlikely that they will drop out or 
withdrawal afterwards given that this is part of a usual care pain management protocol. 
No extra follow up is required for patients and all the outcomes will be part of a usual 
post-op data that will be recorded in Epic.  
 
3.  How many subjects will be enrolled at all sites?    
Answer/Response:  
This is a single site study – enrollment at UVA only. 
 
4.  How many subjects will sign a consent form under this UVA protocol?     
Answer/Response:  
All participants (100)  
Inclusion/Exclusion Criteria 
1.  List the criteria for inclusion  
Answer/Response: 
- 
All female patients who are 18 years or older who will undergo unilateral or bilateral 
abdomen-based free flap breast reconstruction at UVA Medical Center from February 2021 to 
January 2024. 
 
2.  List the criteria for exclusion 
 Answer/Response: Subjects with ages <18 years  


HSR#210033: Effectiveness of Exparel TAP block in breast free flap reconstruction 
 
Version Date: 02/27/21 
Page Number: 3 of 6 
 Allergy to local anesthetic  
 Inability to tolerate usual postoperative pain management regimen (Tylenol, Toradol, 
and Oxycodone PRN) for any reason 
 Subjects who cannot read or understand English  
 Subjects who are pregnant (self-reported) 
 
3.  List any restrictions on use of other drugs or treatments. 
Answer/Response: None 
 
Statistical Considerations 
1. 
Is stratification/randomization involved? 
Answer/Response: Yes 
 
►IF YES, describe the stratification/ randomization scheme. 
 
Answer/Response: 
Random number generator will be used to enroll a subject into control TAP vs. Exparel 
TAP block group after consent is obtained before surgery. Patients will be blinded to 
their TAP block method. Surgeons/PI/ study coordinators will not be blinded to 
randomization. Surgeons/ PI/ study coordinators will have access to the randomization 
scheme. 
 
►IF YES, who will generate the randomization scheme?  
_____ Sponsor 
_____ UVA Statistician.   Insert name Answer/Response: 
_____ UVA Investigational Drug Service (IDS) 
__x___ Other:  Specify   Answer/Response: Study coordinator/ medical staff in 
plastic surgery clinic 
 
2.  What are the statistical considerations for the protocol?  
Answer/Response: 
 This is a randomized, prospective trial that examines the effectiveness of 
Exparel TAP block (mix of Exparel + plain bupivacaine) compared to plain 
bupivacaine TAP block at University of Virginia Medical Center between 
February 2021 and January 2024. Patient information will be kept 
confidential and all identifying information will be removed. Data collected 
will involve:  
o General Demographic Data: age, gender, race, ethnicity, medical and 
surgical history, psychiatric history, medications, drug, smoking, 
alcohol abuse, occupation 
o Type of Reconstructive Procedure: procedure type, laterality 


HSR#210033: Effectiveness of Exparel TAP block in breast free flap reconstruction 
 
Version Date: 02/27/21 
Page Number: 4 of 6 
o TAP block information: liposomal bupivacaine vs. plain bupivacaine  
o Post-operative Narcotic Requirement: total mg of oral opioid use in 
postop period during hospitalization and immediate post-operative 
period (30 days after discharge).  
o Post-operative Data: LOS, pain scores, PONV incidence  
o Complications  
3.  Provide a justification for the sample size used in this protocol.   
Answer/Response:  The primary outcome variable used for sample size calculation is post-
operative narcotic requirement.  Since we are unsure of the exact standard deviation for the 
population in terms of narcotic requirement, but we do have a limited number of patients that 
will be available for the study, we used four different standard deviations to confirm that we 
would have enough patients for 80% power (alpha = 0.05) to detect a difference in groups.  We 
believe that the estimate of the standard deviation is most likely in the 10 mg range, so having 
50 patients in each group would allow us to detect a difference of 5.66 mg between groups at 
80% power. 
Sample sizes  
Standard 
deviation 
Alpha 
Power 
Difference that 
can be detected 
50 50 
1 
0.05 
80% 
0.57 mg 
50 50 
5 
0.05 
80% 
2.83 mg 
50 50 
10 
0.05 
80% 
5.66 mg 
50 50 
15 
0.05 
80% 
8.49 mg 
 
 
4.  What is your plan for primary variable analysis? 
Answer/Response: 
Univariate analysis with Alpha <0.05 considered significant, variables with p<0.1 will be 
included in multivariate analysis to control for potential confounding variables and attempt to 
determine independent factors associated with outcomes. 
Primary outcomes will include post-op recovery data- pain scores and postop narcotic 
requirement (total mg of opioids) both during hospitalization and up to 30 days after discharge.  
Secondary outcomes will include LOS and incidence of PONV.  
 


HSR#210033: Effectiveness of Exparel TAP block in breast free flap reconstruction 
 
Version Date: 02/27/21 
Page Number: 5 of 6 
5.  What is your plan for secondary variable analysis?  
Answer/Response: 
Secondary outcomes will include LOS and PONV.  
Two-sample t-tests or Mann-Whitney U tests will be employed for secondary variable analysis.   
Exploratory multivariate analysis will be employed to determine potential confounding 
variables and attempt to determine the focus for future studies to determine independent 
factors associated with various outcomes.   
6. Have you been working with a statistician in designing this protocol? 
 
Answer/Response:  Yes 
 
IF YES, what is their name?   
Answer/Response: Wendy Novicoff 
 
7.  Will data from multiple sites be combined during analysis?   
Answer/Response: No 
 
Study Procedures-Biomedical Research 
 
1.  What will be done in this protocol?    
Answer/Response:  
Participants will either receive plain bupivacaine TAP block (control/ usual care) or 
Exparel TAP block mix (experimental/ mix of Exparel and plain bupivacaine). Post-op 
data will be recorded in Epic and will be analyzed.  
 
All the subjects will be recruited in UVA plastic surgery clinic when qualifying patients 
come in for pre-operative visits. 
 
2. If this protocol involves study treatment, explain how a subject will be transitioned from 
study treatment when they have completed their participation in the study.   
Answer/Response:  N/A 
 
 
Subject Compliance with Study Procedures 
1.  Explain how the study team will monitor the subject for compliance with the study 
procedures. 
 (e.g. study team will administer study drug/ study interventions, study drug inventory 
of dispensed and returned drug, diary etc.) 
Answer/Response: N/A 
 


HSR#210033: Effectiveness of Exparel TAP block in breast free flap reconstruction 
 
Version Date: 02/27/21 
Page Number: 6 of 6 
2.  Describe criteria for when a subject is considered to be non-compliant with study 
procedures.   
(e.g. subject returns more than 20% of the study drug, subject misses 20% of study 
visits) 
Answer/Response: N/A 
Bibliography 
 
1. 
Brogi E, Kazan R, Cyr S, Giunta F, Hemmerling TMJCJoAJcda. Transversus abdominal plane block 
for postoperative analgesia: a systematic review and meta-analysis of randomized-controlled 
trials. 2016;63(10):1184-1196. 
2. 
Nasrawi Z, Beninato T, Kabata K, Iskandarian S, Zenilman ME, Gorecki P. Laparoscopic-guided 
transversus abdominis plane block following laparoscopic sleeve gastrectomy is associated with 
an earlier return to activity: a study of 271 patients. Surgical endoscopy. 2019. 
3. 
Kupiec A, Zwierzchowski J, Kowal-Janicka J, et al. The analgesic efficiency of transversus 
abdominis plane (TAP) block after caesarean delivery. Ginekologia polska. 2018;89(8):421-424. 
4. 
Pedrazzani C, Menestrina N, Moro M, et al. Local wound infiltration plus transversus abdominis 
plane (TAP) block versus local wound infiltration in laparoscopic colorectal surgery and ERAS 
program. Surgical endoscopy. 2016;30(11):5117-5125. 
5. 
Wheble GA, Tan EK, Turner M, Durrant CA, Heppell S. Surgeon-administered, intra-operative 
transversus abdominis plane block in autologous breast reconstruction: a UK hospital 
experience. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2013;66(12):1665-
1670. 
6. 
Hivelin M, Wyniecki A, Plaud B, Marty J, Lantieri L. Ultrasound-Guided Bilateral Transversus 
Abdominis Plane Block for Postoperative Analgesia after Breast Reconstruction by DIEP Flap. 
2011;128(1):44-55.