Transversus Abdominis Plane Block in Microsurgical Breast Recon w/Abdominal Free Flap in Breast CA

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02601027
• Collaborator: (none)
• Enrollment: 120
• Location: 1
• Arms: 2
• Actual Duration (Months): 67
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The primary objective is to determine if pre-operative transversus abdominis plane (TAP) nerve blocks by continued infusion of local anesthetic post-operatively affects post-operative narcotic usage, as compared to a placebo TAP block, after breast reconstruction surgery.

Condition or Disease	Intervention/Treatment	Phase
Breast - Female	Procedure: Transversus Abdominis Plane (TAP) block; Device: Nimbus Infusion Pump IV Administration; Drug: Bupivacaine infusion; Drug: Acetominophen; Drug: Hydromorphone; Drug: Oxycodone; Drug: Ondansetron	Phase 3

Detailed Description

Primary Objective: The primary objective is to determine if pre-operative transversus abdominis plane (TAP) blocks with continued infusion of local anesthetic post-operatively affect post-operative narcotic usage as compared to a placebo TAP block.

Secondary Objectives:

• Determine if pre-operative TAP blocks with continued infusion of local anesthetic post-operatively affect post-operative pain scores as compared to a placebo TAP block.

• Determine if pre-operative TAP blocks with continued infusion of local anesthetic post-operatively affect anti-emetic usage as compared to a placebo TAP block.

• Determine if pre-operative TAP blocks with continued infusion of local anesthetic post-operatively affect time to ambulation post-operatively as compared to a placebo TAP block.

• Determine if pre-operative TAP blocks with continued infusion of local anesthetic post-operatively affect time to first bowel movement as compared to a placebo TAP block.

• Determine if pre-operative TAP blocks with continued infusion of local anesthetic post-operatively affect patient-reported quality of life as compared to a placebo TAP block.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Phase III Study of Pre-operative Transversus Abdominis Plane Blocks Using the Nimbus Ambulatory Infusion System in Patients Undergoing Abdominal Free Flap-based Breast Reconstruction
• Actual Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Sep 7, 2019
• Actual Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.125% Bupivacaine 0.125% bupivacaine infusion via transversus abdominis plane (TAP) catheter	Procedure: Transversus Abdominis Plane (TAP) block; Device: Nimbus Infusion Pump IV Administration; Drug: Bupivacaine infusion; Other Names: Exparel Marcaine Marcaine Spinal Sensorcaine Sensorcaine-MPF Sensorcaine-MPF Spinal ReadySharp bupivacaine P-Care M ; Drug: Acetominophen; Other Names: Tylenol ; Drug: Hydromorphone; Other Names: Dilaudid Dilaudid-HP Exalgo ; Drug: Oxycodone; Other Names: Oxycontin Xtampza ER Oxaydo Roxicodone ; Drug: Ondansetron; Other Names: Zofran Zofran ODT Zuplenz
Placebo Comparator: Placebo Saline infusion (sham) via transversus abdominis plane (TAP) catheter.	Procedure: Transversus Abdominis Plane (TAP) block; Device: Nimbus Infusion Pump IV Administration; Drug: Acetominophen; Other Names: Tylenol ; Drug: Hydromorphone; Other Names: Dilaudid Dilaudid-HP Exalgo ; Drug: Oxycodone; Other Names: Oxycontin Xtampza ER Oxaydo Roxicodone ; Drug: Ondansetron; Other Names: Zofran Zofran ODT Zuplenz

Outcome Measures

Primary Outcome Measures

1. Post-operative Narcotic Usage [48 hours]

   Narcotic usage was collected for first 48 hours post-operatively after breast reconstruction. The type and amount of each narcotic administered were each converted to the morphine equivalent amount that would be orally administered to achieve the same event. This term is known as the oral morphine equivalent (OME). Narcotic usage was assessed between the group receiving transversus abdominis plane (TAP) nerve block compared to the group receiving the placebo control. The outcome is reported as the observed OME for each group.

Secondary Outcome Measures

1. Post-operative Pain Score [2 days]

   Post-operative Pain Score is defined using Visual Analog Scale (VAS), a patient-reported pain score based on viewing a graphic of a scale 0 to 10, and indicating pain level. Each participant was asked about 48 hours after breast reconstruction to indicate their their perceived pain according on the VAS scale. Higher scores represent greater pain. The outcome is reported as the mean VAS score at 48 hours, with standard deviation.

2. Post-operative Anti-emetic Usage [48 hours]

   Odansetron by intravenous administration was used to control nausea (ie, an anti-emetic drug). Anti-emetic usage was collected for first 48 hours post-operatively after breast reconstruction for the group receiving transversus abdominis plane (TAP) nerve block compared to the group receiving the placebo control. The outcome is reported as the mean quantity of Odansetron in milligrams (mg) administered to each group, with standard deviation.

3. Time to Ambulation [up to 1 week]

   Time to ambulation is defined as the amount of time, from midnight on post-operative Day 1 (ie, first midnight following the surgery), to when the participant to be able to stand up and walk a few steps post-operatively. The assessment of whether or not the participant was able to walk was subjective on the part of the shift nurse (ie, no defined number of steps nor quantitative assessment of gait or stability), and was not explicitly defined in the protocol or elsewhere. The outcome is reported as the time to ambulation in days, with standard deviation, for the group receiving transversus abdominis plane (TAP) nerve block and the group receiving the placebo control.

4. Time to First Bowel Movement [up to 1 week]

   Time to first bowel movement is defined as the amount of time, from midnight on post-operative Day 1 (ie, first midnight following the surgery), to when the participant was to be able to pass a stool post-operatively. The outcome is reported as the time in days, with standard deviation, for the group receiving transversus abdominis plane (TAP) nerve block and the group receiving the placebo control.

5. Quality of Life Measurement [Pre-operative Baseline and Post-operative (2-6 months)]

   Quality of life for the study groups was assessed with the BREAST-Q questionnaire, a survey set of 6 pre-operative questionnaires comprised of 58 questions, and 15 post-operative questionnaires, collected 2 to 6 months after surgery, which is comprised of 109 questions. The results range for the pre-operative and post-operative questionnaire sets is 0 to 269 and 0 to 462, respectively. Because the baseline and post-operative domains are different, the BREAST-Q survey is not a measure of quality of life change over time. The Breast Q questionnaire was validated by Pusic, et al (citation provided). Higher scores for a domain represents better quality of life. The outcome is reported as the mean for each group and timepoint, with standard deviation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Prior diagnosis or presumed diagnosis of breast cancer or undergoing prophylactic treatment.

• Greater than 18 years old.

• Female.

• Undergoing microsurgical breast reconstruction with abdominal free flap.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• True allergy to local anesthetics or opioids.

• History of addiction to narcotics within the last 24 months

• History of chronic pain on opioids within the last 24 months.

• Specific mental health issues such as schizophrenia or bipolar disorder.

• Patients who are pregnant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Gordon K Lee, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 28, 2018

More Information

Publications

• Mundy LR, Homa K, Klassen AF, Pusic AL, Kerrigan CL. Breast Cancer and Reconstruction: Normative Data for Interpreting the BREAST-Q. Plast Reconstr Surg. 2017 May;139(5):1046e-1055e. doi: 10.1097/PRS.0000000000003241.
• Pusic AL, Klassen AF, Scott AM, Klok JA, Cordeiro PG, Cano SJ. Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q. Plast Reconstr Surg. 2009 Aug;124(2):345-353. doi: 10.1097/PRS.0b013e3181aee807.
• Voineskos SH, Klassen AF, Cano SJ, Pusic AL, Gibbons CJ. Giving Meaning to Differences in BREAST-Q Scores: Minimal Important Difference for Breast Reconstruction Patients. Plast Reconstr Surg. 2020 Jan;145(1):11e-20e. doi: 10.1097/PRS.0000000000006317.

• Responsible Party: Gordon Kwanlyp Lee, Professor of Surgery (Plastic and Reconstructive Surgery), Stanford University
• ClinicalTrials.gov Identifier: NCT02601027
• Other Study ID Numbers: IRB-34315; BRS0058
• First Posted: Nov 10, 2015
• Last Update Posted: Sep 23, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Acetaminophen; Oxycodone; Hydromorphone; Ondansetron; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	0.125% Bupivacaine	Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
Period Title: Registration to Surgery
STARTED	64	56
COMPLETED	44	46
NOT COMPLETED	20	10
Period Title: Registration to Surgery
STARTED	44	46
COMPLETED	44	46
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	0.125% Bupivacaine	Placebo	Total
Arm/Group Description	0.125% bupivacaine infusion via transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) via transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Acetominophen Hydromorphone Oxycodone Ondansetron	Total of all reporting groups
Overall Participants	64	56	120
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	58 90.6%	49 87.5%	107 89.2%
>=65 years	6 9.4%	7 12.5%	13 10.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.24 (9.58)	52.11 (10.50)	51.11 (9.98)
Sex: Female, Male (Count of Participants)
Female	64 100%	56 100%	120 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.8%	1 0.8%
Asian	8 12.5%	8 14.3%	16 13.3%
Native Hawaiian or Other Pacific Islander	1 1.6%	0 0%	1 0.8%
Black or African American	3 4.7%	2 3.6%	5 4.2%
White	44 68.8%	38 67.9%	82 68.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	8 12.5%	7 12.5%	15 12.5%
Region of Enrollment (participants) [Number]
United States	64 100%	56 100%	120 100%

Outcome Measures

1. Primary Outcome

Title	Post-operative Narcotic Usage
Description	Narcotic usage was collected for first 48 hours post-operatively after breast reconstruction. The type and amount of each narcotic administered were each converted to the morphine equivalent amount that would be orally administered to achieve the same event. This term is known as the oral morphine equivalent (OME). Narcotic usage was assessed between the group receiving transversus abdominis plane (TAP) nerve block compared to the group receiving the placebo control. The outcome is reported as the observed OME for each group.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.125% Bupivacaine	Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
Measure Participants	44	46
Mean (Standard Deviation) [milligrams (mg)]	139.3 (117.2)	169.2 (136.5)

2. Secondary Outcome

Title	Post-operative Pain Score
Description	Post-operative Pain Score is defined using Visual Analog Scale (VAS), a patient-reported pain score based on viewing a graphic of a scale 0 to 10, and indicating pain level. Each participant was asked about 48 hours after breast reconstruction to indicate their their perceived pain according on the VAS scale. Higher scores represent greater pain. The outcome is reported as the mean VAS score at 48 hours, with standard deviation.
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.125% Bupivacaine	Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
Measure Participants	44	46
Mean (Standard Deviation) [units on a scale]	3.76 (1.72)	3.96 (2.14)

3. Secondary Outcome

Title	Post-operative Anti-emetic Usage
Description	Odansetron by intravenous administration was used to control nausea (ie, an anti-emetic drug). Anti-emetic usage was collected for first 48 hours post-operatively after breast reconstruction for the group receiving transversus abdominis plane (TAP) nerve block compared to the group receiving the placebo control. The outcome is reported as the mean quantity of Odansetron in milligrams (mg) administered to each group, with standard deviation.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.125% Bupivacaine	Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
Measure Participants	44	46
Mean (Standard Deviation) [milligrams (mg)]	5.14 (5.30)	9.93 (13.74)

4. Secondary Outcome

Title	Time to Ambulation
Description	Time to ambulation is defined as the amount of time, from midnight on post-operative Day 1 (ie, first midnight following the surgery), to when the participant to be able to stand up and walk a few steps post-operatively. The assessment of whether or not the participant was able to walk was subjective on the part of the shift nurse (ie, no defined number of steps nor quantitative assessment of gait or stability), and was not explicitly defined in the protocol or elsewhere. The outcome is reported as the time to ambulation in days, with standard deviation, for the group receiving transversus abdominis plane (TAP) nerve block and the group receiving the placebo control.
Time Frame	up to 1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.125% Bupivacaine	Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
Measure Participants	44	46
Mean (Standard Deviation) [days]	1.28 (0.52)	1.45 (0.62)

5. Secondary Outcome

Title	Time to First Bowel Movement
Description	Time to first bowel movement is defined as the amount of time, from midnight on post-operative Day 1 (ie, first midnight following the surgery), to when the participant was to be able to pass a stool post-operatively. The outcome is reported as the time in days, with standard deviation, for the group receiving transversus abdominis plane (TAP) nerve block and the group receiving the placebo control.
Time Frame	up to 1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.125% Bupivacaine	Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
Measure Participants	44	46
Mean (Standard Deviation) [days]	1.67 (1.08)	1.62 (0.99)

6. Secondary Outcome

Title	Quality of Life Measurement
Description	Quality of life for the study groups was assessed with the BREAST-Q questionnaire, a survey set of 6 pre-operative questionnaires comprised of 58 questions, and 15 post-operative questionnaires, collected 2 to 6 months after surgery, which is comprised of 109 questions. The results range for the pre-operative and post-operative questionnaire sets is 0 to 269 and 0 to 462, respectively. Because the baseline and post-operative domains are different, the BREAST-Q survey is not a measure of quality of life change over time. The Breast Q questionnaire was validated by Pusic, et al (citation provided). Higher scores for a domain represents better quality of life. The outcome is reported as the mean for each group and timepoint, with standard deviation.
Time Frame	Pre-operative Baseline and Post-operative (2-6 months)

Outcome Measure Data

Analysis Population Description

Most participants were lost to follow-up, and did not return the case report form (CRF) for this patient-reported Quality of Life (QoL) data

Arm/Group Title	0.125% Bupivacaine	Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron	Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
Measure Participants	10	7
Pre-operative baseline	97.30 (17.61)	99.08 (20.73)
Post-operative (2 to 6 month)	342.11 (26.42)	358.00 (16.83)

Adverse Events

Time Frame	Through 7 days post-operative
Arm/Group Title	0.125% Bupivacaine		Placebo
Arm/Group Description	0.125% bupivacaine infusion through transversus abdominis plane (TAP) catheter Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron		Saline infusion (sham) for transversus abdominis plane (TAP) catheter. Transversus Abdominis Plane (TAP) block Nimbus Infusion Pump IV Administration Bupivacaine infusion Acetominophen Hydromorphone Oxycodone Ondansetron
All Cause Mortality
	0.125% Bupivacaine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/64 (0%)		0/56 (0%)
Serious Adverse Events
	0.125% Bupivacaine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/64 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	0.125% Bupivacaine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/64 (32.8%)		27/56 (48.2%)
Blood and lymphatic system disorders
Anemia	1/64 (1.6%)	1	4/56 (7.1%)	4
Cardiac disorders
Sinus tachycardia	0/64 (0%)	0	1/56 (1.8%)	1
Gastrointestinal disorders
Nausea	1/64 (1.6%)	1	1/56 (1.8%)	1
Vomiting	0/64 (0%)	0	1/56 (1.8%)	1
General disorders
Edema Limbs	0/64 (0%)	0	1/56 (1.8%)	1
Fever	0/64 (0%)	0	2/56 (3.6%)	2
Localized Edema	1/64 (1.6%)	1	0/56 (0%)	0
Infections and infestations
Otitis media	1/64 (1.6%)	1	0/56 (0%)	0
Shingles	1/64 (1.6%)	1	0/56 (0%)	0
Upper respiratory infection	0/64 (0%)	0	1/56 (1.8%)	1
Urinary Tract Infection	1/64 (1.6%)	1	0/56 (0%)	0
Injury, poisoning and procedural complications
Bruising	1/64 (1.6%)	1	1/56 (1.8%)	1
Wound complication	1/64 (1.6%)	1	0/56 (0%)	0
Investigations
Urine output decreased	0/64 (0%)	0	1/56 (1.8%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Chest wall necrosis, specify	1/64 (1.6%)	1	0/56 (0%)	0
Muscle cramp	1/64 (1.6%)	1	0/56 (0%)	0
Pain in extremity	0/64 (0%)	0	1/56 (1.8%)	1
Nervous system disorders
Headache	1/64 (1.6%)	1	0/56 (0%)	0
Peripheral sensory neuropathy	1/64 (1.6%)	1	1/56 (1.8%)	1
Vasovagal reaction	0/64 (0%)	0	1/56 (1.8%)	1
Psychiatric disorders
Anxiety	0/64 (0%)	0	1/56 (1.8%)	1
Skin and subcutaneous tissue disorders
Bullous dermatitis	1/64 (1.6%)	1	1/56 (1.8%)	1
Pruritus	0/64 (0%)	0	1/56 (1.8%)	1
Skin and subcutaneous tissue disorders - Other, specify	1/64 (1.6%)	1	1/56 (1.8%)	1
Skin ulceration	0/64 (0%)	0	1/56 (1.8%)	1
Vascular disorders
Hematoma	5/64 (7.8%)	5	4/56 (7.1%)	4
Hypotension	1/64 (1.6%)	1	2/56 (3.6%)	2
Thromboembolic event	1/64 (1.6%)	1	0/56 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.