Parasternal Nerve Block in Cardiac Patients

• ClinicalTrials.gov Identifier: NCT01826851
• Recruitment Status: Completed
• First Posted: April 9, 2013
• Results First Posted: August 1, 2018
• Last Update Posted: August 1, 2018
• Sponsor: Peter A Knight
• Information provided by (Responsible Party): Peter A Knight, University of Rochester

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease; Pain, Postoperative	Drug: Exparel; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Parasternal Intercostal Nerve Block in Post-Cardiac Surgery Patients: A Randomized, Controlled Trial of Extended-release Liposomal Bupivacaine (Exparel) Versus Placebo
• Study Start Date: March 2013
• Actual Primary Completion Date: June 2017
• Actual Study Completion Date: June 2017

Arms and Interventions

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 Name: Preservative-free normal saline

Outcome Measures

Primary Outcome Measures :

1. Median Cumulative Morphine Equivalent [ Time Frame: Outcome was measured at 1,2,4,8,12,24,36,48,60, and 72 hours post intercostal nerve block. ]
   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.
2. Median Pain Levels [ Time Frame: Outcome was measured at 1,2,4,8,12,24,36,48,60, and 72 hours post intercostal nerve block. ]
   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.

Secondary Outcome Measures :

1. Time to Extubation (Hours) [ Time Frame: 77 hours ]
   Time to remove endotracheal tube following surgery.
2. ICU Length of Stay (Hours) [ Time Frame: 135 hours ]
   Duration of time spent in the intensive care unit postoperatively.
3. Time to First Bowel Movement (Days) [ Time Frame: 35 days ]
   Time to first bowel movement following surgery.
4. Hospital Length of Stay (Days) [ Time Frame: 25 days ]
   Duration of time spent in the hospital following surgery.
5. Time to Return to Work or Daily Activities [ Time Frame: 36 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, New York

University of Rochester Medical Center

Rochester, New York, United States, 14642

Sponsors and Collaborators

Peter A Knight

Investigators

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

  Study Documents (Full-Text)

Documents provided by Peter A Knight, University of Rochester:

Study Protocol and Statistical Analysis Plan  [PDF] February 15, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Peter A Knight, Professor, Cardiac Surgery, University of Rochester
• ClinicalTrials.gov Identifier: NCT01826851
• Other Study ID Numbers: RSRB 00044181
• First Posted: April 9, 2013
• Results First Posted: August 1, 2018
• Last Update Posted: August 1, 2018
• Last Verified: July 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peter A Knight, University of Rochester:

Pain management; Anesthetic, local; Nerve blockade; Coronary Artery Bypass Surgery; Analgesics, opioid; Postoperative complications; Bupivacaine

Additional relevant MeSH terms:

Coronary Artery Disease; Pain, Postoperative; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Bupivacaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents