Intercostal Liposomal Bupivacaine for the Management of Blunt Chest Wall Trauma

• Sponsor: University of Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT02749968
• Collaborator: United States Air Force (U.S. Fed)
• Enrollment: 100
• Location: 1
• Arms: 2
• Actual Duration (Months): 33.8
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

This is a study of liposomal bupivacaine for pain control in patients with blunt chest wall trauma.

Condition or Disease	Intervention/Treatment	Phase
Blunt Chest Wall Trauma; Rib Fracture; Sternal Fracture	Drug: Liposomal bupivacaine; Drug: 0.9% sodium chloride	Phase 2

Detailed Description

The purpose of this study is to evaluate the efficacy of liposomal bupivacaine to provide analgesia via paravertebral intercostal nerve block following significant blunt chest trauma, minimizing adverse outcomes, length of stay and overall narcotic use. The primary outcome of the study is to compare requirements between the bupivacaine group and a standard-of-care group.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Intercostal Liposomal Bupivacaine for the Management of Blunt Chest Wall Trauma
• Actual Study Start Date: Mar 9, 2018
• Actual Primary Completion Date: Jan 1, 2021
• Actual Study Completion Date: Jan 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: 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
Placebo Comparator: 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	Drug: 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; Other Names: 0.9% saline

Outcome Measures

Primary Outcome Measures

1. Opioid Requirement at 24 Hours Post-randomization [24 hours following randomization.]

   Opioid requirement (in morphine equivalents) at 24 hours post-randomization

2. Opioid Requirement at 48 Hours Post-randomization. [48 hours following randomization.]

   Opioid requirement (in morphine equivalents) at 48 hours post-randomization

3. Opioid Requirement at 72 Hours Post-randomization [72 hours following randomization.]

   Opioid requirement (in morphine equivalents) at 72 hours post-randomization

4. Opioid Requirement at 96 Hours Post-randomization [96 hours following randomization.]

   Opioid requirement (in morphine equivalents) at 96 hours post-randomization

Secondary Outcome Measures

1. Development of Pneumonia [96 hours following randomization]

   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.

2. Self-reported Pain at 96 Hours Post-randomization [At 96 hours post-randomization]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Anticipated length of stay of at least 72 hours

• Blunt chest wall trauma with two or more rib or sternal fractures

• Demonstrated ability to achieve > 50% predicted inspiratory capacity based on ideal body weight using IS within the first 24 hours of admission

Exclusion Criteria:

• Known allergy to bupivacaine

• Respiratory failure requiring intubation within 24 hours prior to enrollment

• Known or suspected atrioventricular nodal blockade process requiring cardiology evaluation or pacemaker placement

• Hemodynamic instability (defined as new intravenous vasopressor or inotrope requirement or mean arterial pressure < 55 mmHg)

• Signs of active myocardial ischemia or non-ST elevation MI

• 20 rib fractures

• Weight < 50 kg or > 150 kg

• Pregnancy

• Incarceration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45216

Sponsors and Collaborators

• University of Cincinnati
• United States Air Force

Investigators

• Principal Investigator: Michael D Goodman, MD, Department of Surgery, University of Cincinnati

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 24, 2016

More Information

Publications

None provided.

• Responsible Party: Michael Goodman, instructor, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT02749968
• Other Study ID Numbers: Droege 2016
• First Posted: Apr 25, 2016
• Last Update Posted: Apr 4, 2022
• Last Verified: Mar 1, 2022

• 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: No
• Additional relevant MeSH terms: Fractures, Bone; Wounds and Injuries; Rib Fractures; Bupivacaine

Study Results

Participant Flow

Pre-assignment Detail

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	25	25
COMPLETED	50	50
NOT COMPLETED	0	0

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 Participants	50	50	100
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	40 80%	40 80%	80 80%
>=65 years	10 20%	10 20%	20 20%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (18)	61 (18)	60 (18)
Sex: Female, Male (Count of Participants)
Female	25 50%	22 44%	47 47%
Male	25 50%	28 56%	53 53%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	50 100%	50 100%	100 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Incentive spirometry (Liters/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liters/min]	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
Measure Participants	50	50
Mean (Standard Deviation) [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
Measure Participants	50	50
Mean (Standard Deviation) [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
Measure Participants	50	50
Mean (Standard Deviation) [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
Measure Participants	50	50
Mean (Standard Deviation) [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
Measure Participants	50	50
Count of Participants [Participants]	3 6%	1 2%

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
Measure Participants	50	50
Mean (Standard Deviation) [score on a scale]	6.32 (2.73)	6.44 (2.93)

Adverse Events

Time Frame	96 hours
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)
Serious Adverse Events
	Liposomal Bupivacaine		0.9% Sodium Chloride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/50 (8%)		2/50 (4%)
Respiratory, thoracic and mediastinal disorders
pneumothorax	1/50 (2%)		1/50 (2%)
intubation	3/50 (6%)		1/50 (2%)
Other (Not Including Serious) Adverse Events
	Liposomal Bupivacaine		0.9% Sodium Chloride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)

Limitations/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.