Parasternal Nerve Block in Cardiac Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Coronary Artery Disease, Pain, Postoperative

Intervention / Treatment
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* Drug: Exparel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exparel<br>266 mg Exparel, single-dose injection. | Drug: Exparel<br>* 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.<br>* Other names: Bupivacaine liposome extended-release injectable suspension;|
| Placebo Comparator: Placebo<br>0.9% Normal saline, single-dose injection. | Drug: Placebo<br>* 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.<br>* Other names: Preservative-free normal saline;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthetic, local, Pain management, Nerve blockade, Coronary Artery Bypass Surgery, Analgesics, opioid, Postoperative complications, Bupivacaine