Trial Outcomes & Findings for Intercostal Nerve Block With Liposome Bupivacaine in Subjects Undergoing Posterolateral Thoracotomy (NCT NCT01802411)

Last Updated: 2021-07-12

Results Overview

AUC of pain intensity scores at rest through 72 hours postsurgery. Participants assumed a resting position that did not exacerbate his or her postsurgical pain. Pain intensity scores were measured at baseline and 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours postsurgery, at first request for rescue pain medication, and on day 12 using the numeric rating scale at rest (NRS-R; 0=no pain and 10=worst possible pain).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

191 participants

Primary outcome timeframe

0-72 hours postsurgery

Results posted on

2021-07-12

Participant Flow

Participant milestones

Participant milestones
Measure	EXPAREL 266 mg Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) EXPAREL 266 mg	Placebo Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) Placebo
Overall Study STARTED	96	95
Overall Study COMPLETED	82	74
Overall Study NOT COMPLETED	14	21

Reasons for withdrawal

Reasons for withdrawal
Measure	EXPAREL 266 mg Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) EXPAREL 266 mg	Placebo Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) Placebo
Overall Study Death	2	1
Overall Study Adverse Event	2	7
Overall Study Lack of Efficacy	8	10
Overall Study Withdrawal by Subject	0	2
Overall Study Planned pleurodesis as part of the proc	1	0
Overall Study Surgery aborted after bronchoscopy	1	0
Overall Study Proc changed to video-asst thorascopic	0	1

Baseline Characteristics

Intercostal Nerve Block With Liposome Bupivacaine in Subjects Undergoing Posterolateral Thoracotomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EXPAREL 266 mg n=94 Participants Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) EXPAREL 266 mg	Placebo n=91 Participants Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) Placebo	Total n=185 Participants Total of all reporting groups
Age, Continuous	57.9 years STANDARD_DEVIATION 12.71 • n=5 Participants	58.5 years STANDARD_DEVIATION 13.03 • n=7 Participants	58.2 years STANDARD_DEVIATION 12.84 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	60 Participants n=7 Participants	124 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	90 Participants n=5 Participants	88 Participants n=7 Participants	178 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	0 Participants n=7 Participants	0 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	94 Participants n=5 Participants	91 Participants n=7 Participants	185 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
Region of Enrollment United States	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Poland	38 participants n=5 Participants	32 participants n=7 Participants	70 participants n=5 Participants
Region of Enrollment Bulgaria	20 participants n=5 Participants	28 participants n=7 Participants	48 participants n=5 Participants
Region of Enrollment Czechia	17 participants n=5 Participants	18 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment Georgia	17 participants n=5 Participants	10 participants n=7 Participants	27 participants n=5 Participants
American Society of Anesthesiologists (ASA) classification 1	32 Participants n=5 Participants	24 Participants n=7 Participants	56 Participants n=5 Participants
American Society of Anesthesiologists (ASA) classification 2	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
American Society of Anesthesiologists (ASA) classification 3	14 Participants n=5 Participants	17 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0-72 hours postsurgery

Population: The efficacy population included all participants who received study drug, with analysis based on randomized treatment

Outcome measures

Outcome measures
Measure	EXPAREL 266 mg n=94 Participants Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) EXPAREL 266 mg	Placebo n=91 Participants Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) Placebo
Area Under the Curve (AUC) of Pain Intensity at Rest Through 72 Hours	472.1 score on a scale * hr Standard Error 37.19	459.0 score on a scale * hr Standard Error 36.57

SECONDARY outcome

Timeframe: 0-72 hours postsurgery

Population: The efficacy population included all participants who received study drug, with analysis based on randomized treatment

Total postsurgical opioid consumption (morphine equivalent) through 72 hours postsurgery

Outcome measures

Outcome measures
Measure	EXPAREL 266 mg n=94 Participants Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) EXPAREL 266 mg	Placebo n=91 Participants Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) Placebo
Total Postsurgical Opioid Consumption Through 72 Hours	70.88 mg morphine equivalent dose Standard Deviation 37.537	71.38 mg morphine equivalent dose Standard Deviation 39.418

SECONDARY outcome

Timeframe: 72 hours postsurgery

Population: Time to first use of opioid rescue medication through 72 hours postsurgery, calculated as the date and time of first opioid use minus the date and time of the end of surgery.

Time to first use of opioid rescue medication through 72 hours postsurgery, calculated as the date and time of first opioid use minus the date and time of the end of surgery.

Outcome measures

Outcome measures
Measure	EXPAREL 266 mg n=94 Participants Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) EXPAREL 266 mg	Placebo n=91 Participants Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) Placebo
Time to First Opioid Rescue Through 72 Hours Postsurgery	1.1 hours Interval 0.08 to 72.0	0.7 hours Interval 0.1 to 72.0

Adverse Events

EXPAREL 266 mg

Serious events: 12 serious events

Other events: 63 other events

Deaths: 2 deaths

Placebo

Serious events: 10 serious events

Other events: 55 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	EXPAREL 266 mg n=94 participants at risk Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) EXPAREL 266 mg	Placebo n=91 participants at risk Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) Placebo
Cardiac disorders Atrial fibrillation	2.1% 2/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	6.6% 6/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
General disorders Pyrexia	17.0% 16/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	13.2% 12/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Vascular disorders Hypertension	10.6% 10/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	5.5% 5/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Vascular disorders Hypotension	2.1% 2/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	6.6% 6/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Gastrointestinal disorders Nausea	9.6% 9/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	7.7% 7/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Gastrointestinal disorders Vomiting	9.6% 9/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	8.8% 8/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Gastrointestinal disorders Constipation	7.4% 7/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	4.4% 4/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
General disorders Fatigue	9.6% 9/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	4.4% 4/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Psychiatric disorders Confusional state	7.4% 7/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	4.4% 4/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Nervous system disorders Dysgeusia	7.4% 7/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	2.2% 2/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.
Skin and subcutaneous tissue disorders Pruritus generalized	2.1% 2/94 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.	5.5% 5/91 • From time of randomization through the day 30 follow-up contact The safety population included all participants who received study drug, with analysis based on actual treatment received. Treatment-emergent adverse events that were solicited from the neurological assessment or from the opioid-related AE questionnaire were included in this table.

Additional Information

Pacira Medical Information

Pacira Pharmaceuticals, Inc.

Phone: Pacira Pharmaceuticals, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any proposed publication/presentation of study-related information is subject to advance review by the Sponsor ≥60 days before intended submission/presentation. Investigator/institution shall amend publication/presentation as needed to address errors or confidential information identified by the Sponsor. If requested in writing by the Sponsor, investigator/institution shall withhold publication for an additional 90 days.
Publication restrictions are in place

Restriction type: OTHER