Parasternal Nerve Block in Cardiac Patients

Parasternal Intercostal Nerve Block in Post-Cardiac Surgery Patients: A Randomized, Controlled Trial of Extended-release Liposomal Bupivacaine (Exparel) Versus Placebo

Exparel is a new local analgesic (numbing medication) that is intended to be longer acting than currently available local analgesics. The purpose of this study is to determine whether use of Exparel to numb the nerves along the breastbone after open heart surgery, will decrease pain and pain medication use after surgery.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Pain, Postoperative
• Intervention / Treatment: Drug: Exparel; Drug: Placebo

Detailed Description

This is a Phase 2, single-institution, randomized, double-blind, parallel-group, placebo-controlled trial of patients undergoing a median sternotomy for primary cardiopulmonary bypass grafting (CABG) surgery.

78 subjects (39 per treatment arm) will be randomized in a 1:1 ratio to receive a single-dose, parasternal nerve block with either 266 mg Exparel or placebo (0.9% normal saline solution). The nerve blocks will be performed under direct visualization at the end of surgery, just prior to sternal closure.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years old
• non-emergent coronary artery bypass grafting surgery (on and off pump)
• median sternotomy

Exclusion Criteria:

• Concomitant cardiac procedures (e.g. aortic valve repair/replacement, mitral valve repair/replacement, aortic root replacements).
• Redo sternotomy.
• < 50 kg (Exparel® is currently only approved in patients > 50 kg).
• Pregnant or nursing
• History of alcohol, narcotic or illicit drug abuse
• Participation in another study evaluating investigational medications within the past 30 days
• Taking narcotic analgesics within 3 days pre-operatively or perioperative stress-dose steroids.
• Chronic non-cardiac pain (e.g. lower back pain, fibromyalgia) requiring narcotic analgesics.
• Pre-operative mild liver insufficiency as defined by liver function tests [(i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST)] ≥ 1.5 times the upper limit of normal (ULN: ALT: 0-35 U/L, AST: 0-35 U/L, Alk Phos 35-105 U/L, Total bilirubin: 0-1.2 mg/dL)
• Pre-operative mild renal insufficiency (Cr ≥ 1.5 mg/dL)
• Allergy to amide-type anesthetics
• Recurrent ventricular arrhythmias, low cardiac output requiring inotrope and/or intra-aortic balloon pump support, left ventricular ejection fraction < 30% at time of pre-operative screening/evaluation.
• Unable to provide informed consent or unable to understand how to use pain rating scales.
• Inability to understand or operate the patient-controlled analgesia (PCA) machine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Exparel; 266 mg Exparel, single-dose injection.	Drug: Exparel; Patients in this group will receive 266 mg Exparel diluted with 0.9% normal saline to a total volume of 50 mL and administered via parasternal intercostal nerve block prior to sternal closure. Post-operatively, patients will receive IV fentanyl as needed in the ICU while still intubated. A fentanyl PCA pump will be set up post-extubation as soon as possible and prior to the patient leaving the ICU.; Other Names: SKY0402; Bupivacaine liposome extended-release injectable suspension
PLACEBO_COMPARATOR: Placebo; 0.9% Normal saline, single-dose injection.	Drug: Placebo; Patients in this group will receive 50 mL of 0.9% normal saline as a parasternal intercostal nerve block prior to sternal closure. Post-surgical pain management will be the same as for the Exparel group.; Other Names: Preservative-free normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Cumulative Morphine Equivalent	The cumulative opioid requirement is reported as morphine equivalent. The total amount of narcotics required by the subjects in the Exparel group and placebo group were measured at 1,2,4,8,12,24,36,48,60, and 72 hours post-injection of Exparel or 0.9% normal saline. The amounts were analyzed and are reported as morphine equivalents.	Outcome was measured at 1,2,4,8,12,24,36,48,60, and 72 hours post intercostal nerve block.
Median Pain Levels	The pain scores of the subjects in the Exparel group and placebo group were measured at 1,2,4,8,12,24,36,48,60, and 72 hours post-injection of Exparel or 0.9% normal saline. The pain scores were reported on a scale of 0 - 10. 0 being no pain. 10 being the worst pain.	Outcome was measured at 1,2,4,8,12,24,36,48,60, and 72 hours post intercostal nerve block.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Extubation (Hours)	Time to remove endotracheal tube following surgery.	77 hours
ICU Length of Stay (Hours)	Duration of time spent in the intensive care unit postoperatively.	135 hours
Time to First Bowel Movement (Days)	Time to first bowel movement following surgery.	35 days
Hospital Length of Stay (Days)	Duration of time spent in the hospital following surgery.	25 days
Time to Return to Work or Daily Activities	Time to return to work or daily activities following surgery will be assessed at postoperative clinic follow up or during a follow up telephone interview.	36 days

Collaborators and Investigators

• Sponsor: Peter A Knight
• Investigators: Principal Investigator: Peter A Knight, MD, University of Rochester

Publications and helpful links

General Publications

• Lee CY, Robinson DA, Johnson CA Jr, Zhang Y, Wong J, Joshi DJ, Wu TT, Knight PA. A Randomized Controlled Trial of Liposomal Bupivacaine Parasternal Intercostal Block for Sternotomy. Ann Thorac Surg. 2019 Jan;107(1):128-134. doi: 10.1016/j.athoracsur.2018.06.081. Epub 2018 Aug 28.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): June 1, 2017
• Study Completion (ACTUAL): June 1, 2017

Study Registration Dates

• First Submitted: March 25, 2013
• First Submitted That Met QC Criteria: April 6, 2013
• First Posted (ESTIMATE): April 9, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 1, 2018
• Last Update Submitted That Met QC Criteria: July 7, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Postoperative complications; Pain management; Bupivacaine; Coronary Artery Bypass Surgery; Analgesics, opioid; Anesthetic, local; Nerve blockade
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Coronary Disease; Coronary Artery Disease; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: RSRB 00044181

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No