PAIN - Postoperative Analgesia INvestigation

Study Design:

This is a prospective, single-institution, parallel-group, single-blinded,
randomized-controlled, two-arm, effectiveness study comparing bupivacaine liposomal
injectable suspension (Exparel®) versus regular bupivacaine hydrochloride (HCl).

Procedure:

In patients aged 18 and over who require sternotomy, thoracotomy, mini-thoracotomy, or
laparotomy incisions will be screened and consented for potential enrollment. Patients will
be randomized following consenting to either Exparel® or regular bupivacaine hydrochloride
group.

Course of Study:

The study will accrue patients over the course of 4 years.

Enrollment:

Enrollment will consist of all adult patients aged 18 and over undergoing surgical procedures
requiring sternotomy, thoracotomy, mini-thoracotomy, or laparotomy incisions. Patients will
be screened and consented preoperatively. If the patient is deemed eligible and consents to
participate, randomization will occur and the patient will be considered enrolled.

Recruitment:

The target for enrollment will be 280 patients (the study target sample size per power
analysis, but actual enrollment will be greater (330 patients) to account for exclusions for
various reasons in order to achieve the target recruitment).

Risks:

There is a small increased risk to the patients by participating in the study in addition to
a possible chance of breach in patient confidentiality as the study involves evaluation of an
FDA-approved drug. As detailed in the informed consent, the subjects are at risk of
developing adverse effects from Exparel®, described on the drug packet insert and from HCl
Bupivacaine, also described on the drug packet insert. The investigators do not expect any
additional physical risks other than an unintentional disclosure of sensitive patient health
information.

Data Safety Monitoring:

As the Principal Investigator of this study, Dr. Charlton-Ouw from the Department of
Cardiothoracic and Vascular Surgery at The University of Texas at Houston Medical School will
conduct the data safety monitoring of this study. He will annually meet with all other
co-investigators to review the patients enrolled in this study. As part of the data safety
monitoring plan, all patients enrolled until that point in time would be unblinded in order
to review the outcomes. Additionally, in view of the uncertainty attached to the treatment
effects in this heterogeneous population, owing to limited currently available data, an
independent Data Safety Monitoring Committee, will oversee the progress of the trial.

IND#:

The drugs that will be used are already approved by the FDA and do not have IND/IDE#

Proposed Funding Source:

The study is internally funded and is investigator-initiated.

Communication of Study Results:

The communication of study results will occur only between authorized individuals who are
listed to take part in the study through our department. The individuals who will take part
in the study will acknowledge and adhere to the importance of patient safety and the
protection of their private information. The results of this study will be analyzed and
published after the approval of the principal investigator, co-investigators, and
biostatistician in a peer-reviewed scientific journal and/or presented at an
international/national scientific conference or meeting regardless of outcome.

Inclusion Criteria:

- 18 years-old or older, and

- Sternotomy, thoracotomy, laparotomy or mini-thoracotomy incision is planned

- There is reasonable expectation that the patient will be extubated within 24 hours
after surgery

Exclusion Criteria:

- The patient has a known allergy to morphine or any opioid

- The patient has a known chronic pain disorder or takes daily opioid medication > 1
month prior to surgery

- There is anticipated difficulty communicating pain status due to language or other
barriers at the investigator discretion

- High postoperative morbidity index based on preoperative assessment, such as, low
likelihood of extubation within 24 hours, extensive thoracoabdominal aortic aneurysm
(Extent 2 TAAA), preoperative renal insufficiency/failure, etc.