Trial Outcomes & Findings for Efficacy, Safety, and Pharmacokinetics of Brachial Plexus Block With EXPAREL in Shoulder Surgery (NCT NCT02713230)

Last Updated: 2020-12-03

Results Overview

AUC of VAS pain intensity scores through 48 hours, which represents total pain experienced through 48 hours. VAS is a pain scale. The VAS was presented as a straight 10 cm line, where 0 cm is no pain and 10 cm is the worst pain possible. Patients were asked, "How much pain are you experiencing right now? Please place a vertical mark on the line below to indicate the level of pain you are experiencing right now."

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

156 participants

Primary outcome timeframe

0-48 hours

Results posted on

2020-12-03

Participant Flow

Participants were recruited between May 9, 2016 and July 7, 2017 at 16 sites in the US and Europe

"Started" does not include one patient who was a screen failure, was not enrolled, and was randomized to placebo in error.

Participant milestones

Participant milestones
Measure	EXPAREL 133 mg 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	EXPAREL 266 mg 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Placebo 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively
Overall Study STARTED	69	15	71
Overall Study COMPLETED	68	15	71
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy, Safety, and Pharmacokinetics of Brachial Plexus Block With EXPAREL in Shoulder Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EXPAREL 133 mg n=69 Participants 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	EXPAREL 266 mg n=15 Participants 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Placebo n=71 Participants 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Total n=155 Participants Total of all reporting groups
Age, Continuous	60.6 years STANDARD_DEVIATION 9.94 • n=5 Participants	61.4 years STANDARD_DEVIATION 7.73 • n=7 Participants	58.5 years STANDARD_DEVIATION 9.48 • n=5 Participants	59.7 years STANDARD_DEVIATION 9.55 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants	55 Participants n=4 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	8 Participants n=7 Participants	48 Participants n=5 Participants	100 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=5 Participants	15 Participants n=7 Participants	65 Participants n=5 Participants	144 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants	32 Participants n=4 Participants
Race (NIH/OMB) White	53 Participants n=5 Participants	11 Participants n=7 Participants	54 Participants n=5 Participants	118 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment Belgium	7 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants	19 Participants n=4 Participants
Region of Enrollment United States	52 Participants n=5 Participants	10 Participants n=7 Participants	53 Participants n=5 Participants	115 Participants n=4 Participants
Region of Enrollment Denmark	10 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants	21 Participants n=4 Participants
Dominant hand Left hand	10 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	21 Participants n=4 Participants
Dominant hand Right hand	59 Participants n=5 Participants	14 Participants n=7 Participants	61 Participants n=5 Participants	134 Participants n=4 Participants
Visual Analog Scale Pain Score	2.43 units on a scale STANDARD_DEVIATION 2.621 • n=5 Participants	2.51 units on a scale STANDARD_DEVIATION 2.641 • n=7 Participants	2.94 units on a scale STANDARD_DEVIATION 2.514 • n=5 Participants	2.68 units on a scale STANDARD_DEVIATION 2.570 • n=4 Participants
American Society of Anesthesiologists classification 1	15 Participants n=5 Participants	1 Participants n=7 Participants	14 Participants n=5 Participants	30 Participants n=4 Participants
American Society of Anesthesiologists classification 2	36 Participants n=5 Participants	9 Participants n=7 Participants	37 Participants n=5 Participants	82 Participants n=4 Participants
American Society of Anesthesiologists classification 3	18 Participants n=5 Participants	5 Participants n=7 Participants	20 Participants n=5 Participants	43 Participants n=4 Participants
American Society of Anesthesiologists classification Greater than or equal to 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Type of surgery Rotator cuff surgery	50 Participants n=5 Participants	7 Participants n=7 Participants	55 Participants n=5 Participants	112 Participants n=4 Participants
Type of surgery Total shoulder arthroplasty	19 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants	43 Participants n=4 Participants
Nerve block type Interscalene	67 Participants n=5 Participants	15 Participants n=7 Participants	70 Participants n=5 Participants	152 Participants n=4 Participants
Nerve block type Supraclavicular	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: 0-48 hours

Population: Efficacy population: all participants who received study drug and underwent the surgery, with analysis based on randomized treatment. Under protocol amendment 2, the study arm 266 mg dose of EXPAREL was removed from randomization scheme and efficacy endpoints.

Outcome measures

Outcome measures
Measure	EXPAREL 133 mg n=69 Participants 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Placebo n=71 Participants 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively
Area Under the Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores	136.431 cm*hr Standard Error 12.090	254.119 cm*hr Standard Error 11.768

SECONDARY outcome

Timeframe: 0-48 hours

Total postsurgical opioid consumption (converted to IV morphine equivalents) through 48 hours

Outcome measures

Outcome measures
Measure	EXPAREL 133 mg n=69 Participants 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Placebo n=71 Participants 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively
Total Postsurgical Opioid Consumption Through 48 Hours	11.973 mg Standard Error 2.265	54.303 mg Standard Error 10.053

SECONDARY outcome

Timeframe: 0-48 hours

Percentage of participants who did not receive opioid medication through 48 hours

Outcome measures

Outcome measures
Measure	EXPAREL 133 mg n=69 Participants 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Placebo n=71 Participants 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively
Percentage of Opioid-free Participants Through 48 Hours	9 Participants	1 Participants

SECONDARY outcome

Timeframe: 0-48 hours

Time to first opioid rescue medication consumed through 48 hours. Time to rescue was estimated from Kaplan-Meier analysis and presented as quartiles (ie, time to rescue for the first 25% / 50% / 75% of subjects within each treatment group).

Outcome measures

Outcome measures
Measure	EXPAREL 133 mg n=69 Participants 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Placebo n=71 Participants 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively
Time to First Opioid Rescue Through 48 Hours First quartile	0.70 hours Interval 0.52 to 1.37	0.38 hours Interval 0.3 to 0.47
Time to First Opioid Rescue Through 48 Hours Median quartile	4.15 hours Interval 1.52 to 8.5	0.58 hours Interval 0.48 to 0.68
Time to First Opioid Rescue Through 48 Hours Third quartile	18.82 hours Interval 9.73 to 36.4	0.87 hours Interval 0.72 to 1.0

Adverse Events

EXPAREL 133 mg

Serious events: 2 serious events

Other events: 55 other events

Deaths: 0 deaths

EXPAREL 266 mg

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	EXPAREL 133 mg n=69 participants at risk 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	EXPAREL 266 mg n=15 participants at risk 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively	Placebo n=71 participants at risk 20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively
Infections and infestations Clostridium difficile colitis	0.00% 0/69 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	0.00% 0/15 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	1.4% 1/71 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.
Infections and infestations Pneumonia	1.4% 1/69 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	0.00% 0/15 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	0.00% 0/71 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.
Gastrointestinal disorders Pancreatitis	0.00% 0/69 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	6.7% 1/15 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	0.00% 0/71 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.
Metabolism and nutrition disorders Gout	1.4% 1/69 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	0.00% 0/15 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.	0.00% 0/71 • From screening to postsurgical day 29 An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.

Other adverse events

Additional Information

Pacira Medical Information

Pacira Pharmaceuticals, Inc.

Phone: 1-855-397-2467

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results conducted at Site shall not be published before 1st multicenter publication by Sponsor but can proceed if there is no such publication ≤18 months after study completion/termination at all sites and all data have been received. Before submitting manuscript/materials to an outside person/entity, site shall give Sponsor 60 days to review and comment. Site shall, upon request, further delay publication/presentation for ≤120 days to allow Sponsor to protect its interests in Inventions.
Publication restrictions are in place

Restriction type: OTHER