Trial Outcomes & Findings for Trial of Injected Liposomal Bupivacaine vs Bupivacaine Infusion After Surgical Stabilization of Rib Fractures (NCT NCT03305666)

Last Updated: 2021-09-29

Results Overview

The SCARF score is a validated, dynamic tool that ranges from 0-4, with 0 being the best score and 4 being the worst. One point is given for each of the following four parameters: (1) respiratory rate ≥ 20 breaths per minute; (2) numeric pain score ≥ 5; (3) incentive spirometry \< 50% of predicted based upon a nomogram including sex, height, and age; (4) cough deemed inadequate to clear respiratory secretions by respiratory therapists. The parameters used to calculate the SCARF score are summed to create the total 0-4 score and these results were recorded by clinical personnel not involved in the trial. SCARF scores were taken at 10 am daily for all postoperative inpatient hospital days, however due to variance in length of stay, only scores from the first 5 postoperative days were recorded for the purpose of this results analysis. Scores were then aggregated across the patients and timeframe to result in one median score per group.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

36 participants

Primary outcome timeframe

Median SCARF scores were recorded for the first 5 postoperative days.

Results posted on

2021-09-29

Participant Flow

Participants were recruited based on physician referral for surgical stabilization of rib fracture (SSRF) at Denver Health from November 2017 through July 2020.

All 36 patients were enrolled in the study and assigned to groups via a Microsoft Excel randomization.

Participant milestones

Participant milestones
Measure	Bupivacaine Indwelling Catheter Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op	Liposomal Bupivacaine Injection A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8). Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
Overall Study STARTED	18	18
Overall Study COMPLETED	16	18
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Bupivacaine Indwelling Catheter Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op	Liposomal Bupivacaine Injection A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8). Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
Overall Study ORIF cancelled due to patient's cognitive decline, withdrawn from study at this time	2	0

Baseline Characteristics

Trial of Injected Liposomal Bupivacaine vs Bupivacaine Infusion After Surgical Stabilization of Rib Fractures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bupivacaine Indwelling Catheter n=16 Participants Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op	Liposomal Bupivacaine Injection n=18 Participants A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8). Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS	Total n=34 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Age, Continuous	53.3 years n=5 Participants	52.3 years n=7 Participants	52.8 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index (BMI)	26 kg/m^2 n=5 Participants	27.2 kg/m^2 n=7 Participants	26.6 kg/m^2 n=5 Participants
Injury Severity Score (ISS)	19.5 units on a scale n=5 Participants	22.1 units on a scale n=7 Participants	20.8 units on a scale n=5 Participants
Number of Participants with Asthma	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Number of Participants with COPD	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Number of Participants who Use Tobacco	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Admit Glasgow Coma Scale (GCS)	13.3 units on a scale n=5 Participants	13.3 units on a scale n=7 Participants	13.3 units on a scale n=5 Participants

PRIMARY outcome

Timeframe: Median SCARF scores were recorded for the first 5 postoperative days.

Population: All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. Patients who were intubated at 10 am (the time of data reporting) could not be measured on a few factors of this outcome measure and this discrepancy was accounted for in the statistical analysis.

Outcome measures

Outcome measures
Measure	Bupivacaine Indwelling Catheter n=16 Participants Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op	Liposomal Bupivacaine Injection n=18 Participants A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8). Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
Daily Sequential Clinical Assessment of Respiratory Function (SCARF) Score	2 score on a scale Interval 0.0 to 4.0	2 score on a scale Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: Mean narcotic requirement scores were recorded for the first 5 postoperative hospital inpatient days.

Population: All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. The data below is the mean result provided for each of the first 5 postoperative days following surgical intervention.

Narcotic pain medication requirements were recorded daily over the duration of inpatient hospital stay, however due to variance in length of stay, only the first 5 postoperative days were recorded for this analysis. Scores were averaged across patients providing one daily postoperative mean score per treatment group. The narcotics provided to patients varied based on standard of care, so an Equi-Analgesic Scale was used to standardize dosages across narcotic type. A 1:1 ratio for narcotic dosages is calculated with the following measured as equivalent: 1.5 milligrams (mg) of intravenous (IV) Hydromorphone; 7.5 mg of per oral (PO) Hydromorphone; 100 micrograms (mcg) of IV Fentanyl; 10 mg of IV Morphine; 30 mg of PO Morphine; 20 mg of PO Oxycodone (Percocet); and 30 mg of PO Hydrocodone (Vicodin). In the context of this scale, lower scores are best, indicating fewer narcotics required and higher scores are worse indicating the need for more narcotics based on subjective patient pain.

Outcome measures

Outcome measures
Measure	Bupivacaine Indwelling Catheter n=16 Participants Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op	Liposomal Bupivacaine Injection n=18 Participants A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8). Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
Daily Narcotic Requirements Using Equi-analgesic Doses Postoperative Day #5	4.1 units on a scale Standard Deviation 7.4	2.2 units on a scale Standard Deviation 2.3
Daily Narcotic Requirements Using Equi-analgesic Doses Postoperative Day #1	8.8 units on a scale Standard Deviation 13	6.5 units on a scale Standard Deviation 8.5
Daily Narcotic Requirements Using Equi-analgesic Doses Postoperative Day #2	6.8 units on a scale Standard Deviation 10.1	4.0 units on a scale Standard Deviation 6.9
Daily Narcotic Requirements Using Equi-analgesic Doses Postoperative Day #3	4.0 units on a scale Standard Deviation 6.1	2.6 units on a scale Standard Deviation 3.3
Daily Narcotic Requirements Using Equi-analgesic Doses Postoperative Day #4	4.2 units on a scale Standard Deviation 5.7	1.6 units on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: 72 hours

Population: All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. Percentages entered below are based on number of failure occurrences, in this case defined as requiring a secondary LRA.

The failure of LRA for this study was defined as the percentage number of instances a patient required a secondary LRA modality within 72 hours of placement of the primary modality for either treatment arm. Requirement of this secondary LRA was determined by the patients' medical team with criteria based on subjective patient experience of pain.

Outcome measures

Outcome measures
Measure	Bupivacaine Indwelling Catheter n=16 Participants Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op	Liposomal Bupivacaine Injection n=18 Participants A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8). Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
Percentage of Participants Experiencing Failure of Primary Loco-Regional Analgesia (LRA)	18.8 percentage of participants	5.6 percentage of participants

Adverse Events

Bupivacaine Indwelling Catheter

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Liposomal Bupivacaine Injection

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Bupivacaine Indwelling Catheter n=16 participants at risk Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op	Liposomal Bupivacaine Injection n=18 participants at risk A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8). Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
Social circumstances Hospital Readmission	6.2% 1/16 • Number of events 2 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.	0.00% 0/18 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.
Injury, poisoning and procedural complications Hospital Readmission	0.00% 0/16 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.	5.6% 1/18 • Number of events 1 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.
Skin and subcutaneous tissue disorders OR Takeback	6.2% 1/16 • Number of events 1 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.	0.00% 0/18 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.
Social circumstances ED Visit	6.2% 1/16 • Number of events 1 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.	0.00% 0/18 • Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.

Additional Information

Dr. Fredric Pieracci

Denver Health and Hospital Authority

Phone: (303) 436-4029

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place