Comparing Liposomal Bupivacaine Versus Standard Bupivacaine in Colorectal Surgery

Liposomal Bupivacaine Versus Standard Bupivacaine Hydrochloride In Colorectal Surgery

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03702621

Enrollment

Registered

2018-10-11

Start date

2018-08-30

Completion date

2020-03-13

Last updated

2023-05-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colorectal Surgery

Brief summary

The purpose of this study is to compare the difference between two different pain control methods in patients who will be having a colorectal surgery

Detailed description

Quadratus lumborum (QL) blocks will be done intraoperatively after induction. All procedures will be placed under the supervision of the attending anesthesiologist on the acute pain service. All patients will receive 1 gm acetaminophen and 600 mg gabapentin preoperatively. Patients above 70yo will receive 300mg gabapentin. Patient will be randomized to one of the two arms. For the QL block, Shamrock sign consistent of the quadratus lumborum muscle, psoas major muscle, erector spinae muscles and the L4 transverse process will be identified. Under ultrasound guidance with an in-plane technique, the needle will be advanced into the fascial plane between the quadratus lumborum and psoas major muscles. For the liposomal bupivacaine (LB) group, 0.125% bupivacaine 20ml plus Exparel®10ml will then be injected into the fascial plane on each side. For the standard bupivacaine (SB) group. 30ml 0.25% bupivacaine will be injected on each side. Saline will be used for hydro-dissection until the QL block target is confirmed on ultrasound. As part of the enhanced recovery after surgery (ERAS) protocol, all patients will receive ketamine and lidocaine drip during surgery, which is the investigator's current standard of practice. All patients will be scheduled on PO acetaminophen and PO gabapentin daily postoperatively per ERAS protocol. PO oxycodone as needed (PRN) will be started once patients tolerate diet. PRN IV dilaudid may be given for severe breakthrough pain. Opioid usage at 1, 24, 48 and 72 hours after the block will be recorded by a member of the research team. Pain scores at rest and on movement (knee flexion) will be measured by the investigator using Visual Analog Scale (VAS). Nausea will be measured using a categorical scoring system (none=0; mild=1; moderate=2; severe=3). Sedation scores will also be assessed by a member of the study team using a sedation scale (awake and alert=0; quietly awake=1; asleep but easily roused=2; deep sleep=3). All these parameters will be measured at 1, 24, 48 and 72 hours after the QL block and patients will be encouraged to ambulate on postoperative day 1 under supervision. Their ambulation activity will be recorded.

Interventions

DRUGliposomal Bupivacaine

20 mL liposomal bupivacaine are injected into the liposomal bupivacaine group

DRUGBupivacaine Hydrochloride

40 mL of 0.125% bupivacaine hydrochloride are injected into the liposomal bupivacaine group. 60mL of 0.25% bupivacaine hydrochloride are injected into the standard bupivacaine group

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

Both the patients and the research staff doing assessments will be blinded to the randomization.

Intervention model description

1. LB group (Liposomal Bupivacaine) 2. SB group (Standard Bupivacaine)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients undergoing colorectal surgery at Indiana University Hospital * American Society of Anesthesiologists (ASA) class 1, 2, 3 or 4 * Age 18 or older, male or female * Desires Regional anesthesia for postoperative pain control

Exclusion criteria

* Any contraindication for QL block. * History of substance abuse in the past 6 months. * Patients on more than 30mg morphine equivalents of opioids daily. * Any physical, mental or medical conditions which in the opinion of the investigators, may confound quantifying postoperative pain resulting from surgery. * Known allergy or other contraindications to the study medications (Acetaminophen, Gabapentin, Bupivacaine). * Postoperative intubation. * Any BMI greater than 40.0.

Design outcomes

Primary

Measure	Time frame	Description
VAS Score at 72 Hours With Movement	Pain scores will be measured 72 hours after surgery	The VAS score with movement (knee flexion) will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain
VAS Score at 24 Hours at Rest	Pain scores will be measured 24 hours after surgery	The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain
VAS Score at 48 Hours at Rest	Pain scores will be measured 48 hours after surgery	The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain
VAS Score at 48 Hours With Movement	Pain scores will be measured 48 hours after surgery	The VAS score with movement (knee flexion) will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain
VAS Score at 72 Hours at Rest	Pain scores will be measured 72 hours after surgery	The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain
VAS Score at 24 Hours With Movement	Pain scores will be measured 24 hours after surgery	The VAS score with movement (knee flexion) will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain
VAS Score at 1 Hour at Rest	Pain scores will be measured 1 hour after surgery	The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain
VAS Score at 1 Hour With Movement	Pain scores will be measured 1 hour after surgery	The VAS score with movement (knee flexion) will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain

Secondary

Measure	Time frame	Description
Total Opioid Consumption at 24 Hour	Opioid consumption will be measured at 24 hour post op. The total amount will be recorded	Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements
Total Opioid Consumption at 48 Hour	Opioid consumption will be measured at 48 hour post op. The total amount will be recorded	Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements
Total Opioid Consumption at 72 Hour	Opioid consumption will be measured at 72 hour post op. The total amount will be recorded	Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements
Total Opioid Consumption at 1 Hour	Opioid consumption will be measured at 1 hour post op. The total amount will be recorded	Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements

Other

Measure	Time frame	Description
Nausea Scores (None) at 72 Hours	Nausea scores will be measured at 72 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Mild) at 72 Hours	Nausea scores will be measured at 72 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Moderate) at 72 Hours	Nausea scores will be measured at 72 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Severe) at 72 Hours	Nausea scores will be measured at 72 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Sedation Scores (Awake/Alert) at 1 Hour	Sedation scores will be documented at 1 hour post-op.	Sedation scores will be collected by a study team member post operatively up to 3 days per protocol requirements. Determining if patient is awake, alert, quietly awake, asleep and arousable, or deep sleep.
Sedation Scores (Quietly Awake) at 1 Hour	Sedation scores will be documented at 1 hour post-op.	Sedation scores will be collected by a study team member post operatively up to 3 days per protocol requirements. Determining if patient is awake, alert, quietly awake, asleep and arousable, or deep sleep.
Sedation Scores (Asleep/Arousable) at 1 Hour	Sedation scores will be documented at 1 hour post-op.	Sedation scores will be collected by a study team member post operatively up to 3 days per protocol requirements. Determining if patient is awake, alert, quietly awake, asleep and arousable, or deep sleep.
Sedation Scores (Deep Sleep) at 1 Hour	Sedation scores will be documented at 1 hour post-op.	Sedation scores will be collected by a study team member post operatively up to 3 days per protocol requirements. Determining if patient is awake, alert, quietly awake, asleep and arousable, or deep sleep.
Sedation Scores (Awake/Alert) at 24 Hours	Sedation scores will be documented at 24 hours post-op.	Sedation scores will be collected by a study team member post operatively up to 3 days per protocol requirements. Determining if patient is awake, alert, quietly awake, asleep and arousable, or deep sleep.
Sedation Scores (Awake/Alert) at 48 Hours	Sedation scores will be documented at 48 hours post-op.	Sedation scores will be collected by a study team member post operatively up to 3 days per protocol requirements. Determining if patient is awake, alert, quietly awake, asleep and arousable, or deep sleep.
Sedation Scores (Awake/Alert) at 72 Hours	Sedation scores will be documented at 72 hours post-op.	Sedation scores will be collected by a study team member post operatively up to 3 days per protocol requirements. Determining if patient is awake, alert, quietly awake, asleep and arousable, or deep sleep.
Surgery Duration	Duration of Surgery from surgery start time to surgery stop time (usually within 6 hours)	Duration of surgery will be collected per MR of surgeon documentation.
Length of Stay	Time Frame for Admission to Discharge (usually within 3-7 days)	Admission date until Admission Discharge
Nausea Scores (None) at 1 Hour	Nausea scores will be measured at 1 hour post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Time to Bowel Movement	End of Surgery until first reported Bowel movement per MR or patient reported (usually 3 to 5 days)	Hours for End of Surgery to first reported hour of bowel movement
Time to Per Os	Time from end of surgery to time of Os (usually 4-16 hours)	Reported time after surgery to time of Os per MR or patient
Ambulatory Postoperatively	End of Surgery until first reported ambulated postoperatively per MR or patient reported (Usually within 24 hours postop)	Number of patients who ambulated within 24 hours of end of surgery
Time to Flatus	End of Surgery until first reported Flatus (usually within 3 to 5 days)	Hours for End of Surgery to first reported hour of Flatus
Nausea Scores (Mild) at 1 Hour	Nausea scores will be measured at 1 hour post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Moderate) at 1 Hour	Nausea scores will be measured at 1 hour post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Severe) at 1 Hour	Nausea scores will be measured at 1 hour post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (None) at 24 Hours	Nausea scores will be measured at 24 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Mild) at 24 Hours	Nausea scores will be measured at 24 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Moderate) at 24 Hours	Nausea scores will be measured at 24 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Severe) at 24 Hours	Nausea scores will be measured at 24 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (None) at 48 Hours	Nausea scores will be measured at 48 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Mild) at 48 Hours	Nausea scores will be measured at 48 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Moderate) at 48 Hours	Nausea scores will be measured at 48 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe
Nausea Scores (Severe) at 48 Hours	Nausea scores will be measured at 48 hours post-op.	Nausea scores will be collected by a study team member post operatively up to 3 days per protocol. Nausea will be recorded as none, mild, moderate, or severe

Countries

United States

Participant flow

Participants by arm

Arm	Count
Liposomal Bupivacaine LB (Liposomal Bupivacaine) group - This group will be receiving 20 mL EXPAREL (266mg) and 40 mL of 0.125% bupivacaine in total, 30 mL on each side. For the quadratus lumborum (QL) block, Shamrock sign consistent of the quadratus lumborum muscle, psoas major muscle, erector spinae muscles and the L4 transverse process will be identified. Under ultrasound guidance with an in-plane technique, the needle will be advanced into the fascial plane between the quadratus lumborum and psoas major muscles. Local anesthetic will be injected into the plane. liposomal Bupivacaine: 20 mL liposomal bupivacaine are injected into the liposomal bupivacaine group	38
Standard Bupivacaine SB (Standard Bupivacaine) group - This group will be receiving 60 mL of 0.25% bupivacaine in total, 30 mL on each side. For the QL block, Shamrock sign consistent of the quadratus lumborum muscle, psoas major muscle, erector spinae muscles and the L4 transverse process will be identified. Under ultrasound guidance with an in-plane technique, the needle will be advanced into the fascial plane between the quadratus lumborum and psoas major muscles. Local anesthetic will be injected into the plane. Bupivacaine Hydrochloride: 40 mL of 0.125% bupivacaine hydrochloride are injected into the liposomal bupivacaine group. 60mL of 0.25% bupivacaine hydrochloride are injected into the standard bupivacaine group	40
Total	78

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Physician Decision	6	6

Baseline characteristics

Characteristic	Total	Liposomal Bupivacaine	Standard Bupivacaine
Age, Continuous	61.5 years	59 years	62 years
Body Mass Index	26.9 kg/square meter	25.8 kg/square meter	28.7 kg/square meter
Height	170.2 cm	172.7 cm	167.3 cm
No Known Allergies	34 Participants	17 Participants	17 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	5 Participants	1 Participants	4 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	72 Participants	36 Participants	36 Participants
Sex: Female, Male Female	42 Participants	18 Participants	24 Participants
Sex: Female, Male Male	36 Participants	20 Participants	16 Participants
Weight	77.1 kg	76.8 kg	77.5 kg

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 38	0 / 40
other Total, other adverse events	0 / 38	0 / 40
serious Total, serious adverse events	0 / 38	0 / 40

Outcome results

Primary

VAS Score at 1 Hour at Rest

The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain

Time frame: Pain scores will be measured 1 hour after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 1 Hour at Rest	5.0 score on a scale
Standard Bupivacaine	VAS Score at 1 Hour at Rest	3.0 score on a scale

p-value: 0.54Mixed Models Analysis

Primary

VAS Score at 1 Hour With Movement

The VAS score with movement (knee flexion) will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain

Time frame: Pain scores will be measured 1 hour after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 1 Hour With Movement	5.0 score on a scale
Standard Bupivacaine	VAS Score at 1 Hour With Movement	3.0 score on a scale

p-value: 0.59Mixed Models Analysis

Primary

VAS Score at 24 Hours at Rest

The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain

Time frame: Pain scores will be measured 24 hours after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 24 Hours at Rest	4.0 score on a scale
Standard Bupivacaine	VAS Score at 24 Hours at Rest	3.0 score on a scale

p-value: 0.98Mixed Models Analysis

Primary

VAS Score at 24 Hours With Movement

Time frame: Pain scores will be measured 24 hours after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 24 Hours With Movement	7.0 score on a scale
Standard Bupivacaine	VAS Score at 24 Hours With Movement	6.0 score on a scale

p-value: 0.94Mixed Models Analysis

Primary

VAS Score at 48 Hours at Rest

The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain

Time frame: Pain scores will be measured 48 hours after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 48 Hours at Rest	3.0 score on a scale
Standard Bupivacaine	VAS Score at 48 Hours at Rest	2.5 score on a scale

Comparison: P values are from mixed model LS means differences with Sidak adjustment for multiple comparisonsp-value: 0.86Mixed Models Analysis

Primary

VAS Score at 48 Hours With Movement

Time frame: Pain scores will be measured 48 hours after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 48 Hours With Movement	5.0 score on a scale
Standard Bupivacaine	VAS Score at 48 Hours With Movement	5.0 score on a scale

p-value: 1Mixed Models Analysis

Primary

VAS Score at 72 Hours at Rest

The VAS score at rest will be measured by a study team investigator using Visual Analog Scale (VAS). Using a scale of 1-10 for documentation with 10 being the worst pain and 0 being no pain

Time frame: Pain scores will be measured 72 hours after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 72 Hours at Rest	2.0 score on a scale
Standard Bupivacaine	VAS Score at 72 Hours at Rest	2.0 score on a scale

p-value: 0.99Mixed Models Analysis

Primary

VAS Score at 72 Hours With Movement

Time frame: Pain scores will be measured 72 hours after surgery

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	VAS Score at 72 Hours With Movement	4.0 score on a scale
Standard Bupivacaine	VAS Score at 72 Hours With Movement	3.0 score on a scale

p-value: 0.99Mixed Models Analysis

Secondary

Total Opioid Consumption at 1 Hour

Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements

Time frame: Opioid consumption will be measured at 1 hour post op. The total amount will be recorded

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	Total Opioid Consumption at 1 Hour	8.0 morphine equivalent units
Standard Bupivacaine	Total Opioid Consumption at 1 Hour	2.0 morphine equivalent units

p-value: 0.72Mixed Models Analysis

Secondary

Total Opioid Consumption at 24 Hour

Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements

Time frame: Opioid consumption will be measured at 24 hour post op. The total amount will be recorded

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	Total Opioid Consumption at 24 Hour	54.0 morphine equivalent units
Standard Bupivacaine	Total Opioid Consumption at 24 Hour	30.0 morphine equivalent units

p-value: 0.29Mixed Models Analysis

Secondary

Total Opioid Consumption at 48 Hour

Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements

Time frame: Opioid consumption will be measured at 48 hour post op. The total amount will be recorded

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	Total Opioid Consumption at 48 Hour	43.8 morphine equivalent units
Standard Bupivacaine	Total Opioid Consumption at 48 Hour	15.0 morphine equivalent units

p-value: 0.46Mixed Models Analysis

Secondary

Total Opioid Consumption at 72 Hour

Opioid consumption will be collected by a study team member post operatively for 3 days per protocol time requirements

Time frame: Opioid consumption will be measured at 72 hour post op. The total amount will be recorded

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	Total Opioid Consumption at 72 Hour	17.5 morphine equivalent units
Standard Bupivacaine	Total Opioid Consumption at 72 Hour	15.0 morphine equivalent units

p-value: 0.77Mixed Models Analysis

Other Pre-specified

Ambulatory Postoperatively

Number of patients who ambulated within 24 hours of end of surgery

Time frame: End of Surgery until first reported ambulated postoperatively per MR or patient reported (Usually within 24 hours postop)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Liposomal Bupivacaine	Ambulatory Postoperatively	35 Participants
Standard Bupivacaine	Ambulatory Postoperatively	40 Participants

Other Pre-specified

Length of Stay

Admission date until Admission Discharge

Time frame: Time Frame for Admission to Discharge (usually within 3-7 days)

Arm	Measure	Value (MEDIAN)
Liposomal Bupivacaine	Length of Stay	3.5 days
Standard Bupivacaine	Length of Stay	3.1 days

Other Pre-specified