Intercostal Liposomal Bupivacaine for the Management of Blunt Chest Wall Trauma

• ClinicalTrials.gov Identifier: NCT02749968
• Recruitment Status: Completed
• First Posted: April 25, 2016
• Results First Posted: April 4, 2022
• Last Update Posted: April 4, 2022
• Sponsor: University of Cincinnati
• Collaborator: United States Air Force
• Information provided by (Responsible Party): Michael Goodman, University of Cincinnati

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Conditions: Blunt Chest Wall Trauma; Rib Fracture; Sternal Fracture
• Interventions: Drug: Liposomal bupivacaine; Drug: 0.9% sodium chloride
• Enrollment: 100

Participant Flow

Recruitment Details

Pre-assignment Details

To achieve an 80% power with an alpha of 0.05, the goal enrollment was 200 patients. Interim analyses were performed after 50 patients further providing evidence to support the 200 patient goal for enrollment. Due to changes in analgesia protocols away from epidural catheters and a change in exclusion criteria to include those who were candidates for surgical stabilization of rib fractures, as well as the COVID-19 pandemic, enrollment was stopped at 100 patients

Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
Period Title: Overall Study
Started	50	50
Interim Analysis [1]	25	25
Completed	50	50
Not Completed	0	0
[1] Interim safety and efficacy analysis was performed after 25 patients were recruited to each arm.

Baseline Characteristics

Arm/Group Title		Liposomal Bupivacaine	0.9% Sodium Chloride	Total
Arm/Group Description		1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	Total of all reporting groups
Overall Number of Baseline Participants		50	50	100
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	50 participants	100 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	40 80.0%	40 80.0%	80 80.0%
	>=65 years	10 20.0%	10 20.0%	20 20.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	50 participants	50 participants	100 participants
		60 (18)	61 (18)	60 (18)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	50 participants	100 participants
	Female	25 50.0%	22 44.0%	47 47.0%
	Male	25 50.0%	28 56.0%	53 53.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	50 participants	100 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	50 100.0%	50 100.0%	100 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Incentive spirometry; Mean (Standard Deviation); Unit of measure: Liters/min
	Number Analyzed	50 participants	50 participants	100 participants
		17.8 (8.1)	17.6 (6.6)	17.7 (7.39)

Outcome Measures

1. Primary Outcome

Title	Opioid Requirement at 24 Hours Post-randomization
Description	Opioid requirement (in morphine equivalents) at 24 hours post-randomization
Time Frame	24 hours following randomization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description:	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: morphine milligram equivalents
	38 (959)	202 (691)

2. Primary Outcome

Title	Opioid Requirement at 48 Hours Post-randomization.
Description	Opioid requirement (in morphine equivalents) at 48 hours post-randomization
Time Frame	48 hours following randomization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description:	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: morphine milligram equivalents
	298 (1036)	82 (129)

3. Primary Outcome

Title	Opioid Requirement at 72 Hours Post-randomization
Description	Opioid requirement (in morphine equivalents) at 72 hours post-randomization
Time Frame	72 hours following randomization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description:	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: morphine milligram equivalents
	413 (1714)	116 (199)

4. Primary Outcome

Title	Opioid Requirement at 96 Hours Post-randomization
Description	Opioid requirement (in morphine equivalents) at 96 hours post-randomization
Time Frame	96 hours following randomization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description:	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: morphine milligram equivalents
	637 (2012)	39 (56)

5. Secondary Outcome

Title	Development of Pneumonia
Description	Development of pneumonia defined as >100,000 colony forming units/milliliter bacteria on bronchoalveolar lavage or clinically with leukocytosis, pulmonary infiltrate and fever with 96 hours post-randomization.
Time Frame	96 hours following randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description:	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
Overall Number of Participants Analyzed	50	50
Measure Type: Count of Participants; Unit of Measure: Participants
	3 6.0%	1 2.0%

6. Secondary Outcome

Title	Self-reported Pain at 96 Hours Post-randomization
Description	Self-reported pain will be measured using the verbal NRS, a 0-10 ordinal scale. Pain assessments will be reported at 96 hours after enrollment, as this is the reported duration of effect for liposomal bupivacaine. Higher scores (10) indicate more pain, lower scores (0) indicate lower pain.
Time Frame	At 96 hours post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description:	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: score on a scale
	6.32 (2.73)	6.44 (2.93)

Adverse Events

Time Frame	96 hours
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Liposomal Bupivacaine	0.9% Sodium Chloride
Arm/Group Description	1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position Liposomal bupivacaine: 1 mL of liposomal bupivacaine injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position	1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position 0.9% sodium chloride: 1 mL of 0.9% saline injected with a 25-G needle just below each affected rib by the intercostal neurovascular bundle in a paraspinal position
All-Cause Mortality
	Liposomal Bupivacaine	0.9% Sodium Chloride
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/50 (0.00%)	0/50 (0.00%)
Serious Adverse Events
	Liposomal Bupivacaine	0.9% Sodium Chloride
	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/50 (8.00%)	2/50 (4.00%)
Respiratory, thoracic and mediastinal disorders
pneumothorax †	1/50 (2.00%)	1/50 (2.00%)
intubation †	3/50 (6.00%)	1/50 (2.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Liposomal Bupivacaine	0.9% Sodium Chloride
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/50 (0.00%)	0/50 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

• Name/Title: Michael Goodman
• Organization: University of Cincinnati
• Phone: 5135585661
• EMail: michael.goodman@uc.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wallen TE, Singer KE, Makley AT, Athota KP, Janowak CF, Hanseman D, Salvator A, Droege ME, Strilka R, Droege CA, Goodman MD. Intercostal liposomal bupivacaine injection for rib fractures: A prospective randomized controlled trial. J Trauma Acute Care Surg. 2022 Feb 1;92(2):266-276. doi: 10.1097/TA.0000000000003462.

• Responsible Party: Michael Goodman, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT02749968
• Other Study ID Numbers: Droege 2016
• First Submitted: April 18, 2016
• First Posted: April 25, 2016
• Results First Submitted: February 14, 2022
• Results First Posted: April 4, 2022
• Last Update Posted: April 4, 2022