A Study of Postsurgical Pain Control for Lower Extremity Fractures

A Randomized, Single-blinded, Prospective Study of Postsurgical Pain Control After Open Reduction and Internal Fixation of Lower Extremity Fractures With Liposomal Marcaine.

Postsurgical pain may effectively be treated with a multimodal approach that incorporates the use of local anesthetics. Bupivacaine is a local anesthetic that has been proven to be effective at reducing postsurgical pain. Furthermore, this local anesthetic has been shown to reduce opioid use, improve functional outcomes, allow for early mobilization, and decrease hospital length of stay. However, local anesthetics, via wound infiltration, are often short-acting and do not meet the duration of postsurgical pain due to their solubility and protein-binding properties. ExparelTM is an FDA-approved liposomal formulation of bupivacaine that allows for 72 hours of postsurgical analgesia with a single injection. This formulation has been shown to have little to no adverse effects; although some studies have reported adverse effects with the use of ExaprelTM, most frequently being nausea, vomiting, and dizziness. The occurrences of these adverse events were still less than the placebo cohort.

Study Overview

• Status: Withdrawn
• Conditions: Lower Extremity Fractures.
• Intervention / Treatment: Drug: Bupivacaine/Exparel

Detailed Description

All patients undergoing surgical fixation of a lower extremity fracture(s) will be offered the opportunity to enroll in the study. Patients undergoing unilateral or bilateral surgical fixation would be included. Written, informed consent to enrollment will be recorded and included in the patient record. The study is designed around the standard of care for postsurgical pain management. There are no additional costs to the patient strictly related to this study.

Patients will undergo surgical fixation of a lower extremity fracture(s) by one of surgical investigators at a single institution. A sealed, opaque envelope, selected in the pre-operative holding area, will accompany each patient participant to the operating room. The envelope will be opened at the conclusion of the fracture fixation to reveal patient assignment to either study Group 1 or Group 2. Once the total numbers of patients have completed their procedures and follow-up, the study will close.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Ft. Lauderdale, Florida, United States, 33316
      • Broward Health 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:

• Patients over 18 years of age
• Preoperative diagnosis of lower extremity fracture(s) requiring surgical fixation

Exclusion Criteria:

• Allergy to ExparelTM or certain other local anesthetic agents
• Surgery performed at an outside institution or by a different surgeon
• Chronic analgesic users (defined as use of opioid medication >14 days in the past 3 months, or use of non-opioid pain medication >5 times per week
• Pregnant females or females who think they may become pregnant
• Peripheral neuropathy
• Major psychiatric disease
• Inability to comprehend the nature of the study
• Unwillingness to provide signed informed consent
• Markedly abnormal kidney function or renal disease
• Non-English speaking
• Signs or symptoms of compartment syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control- Marcain; Group 1 will receive non-liposomal bupivacaine introduced into the soft tissue surrounding the fracture at the conclusion of the surgery.	Drug: Bupivacaine/Exparel; The opaque envelope, which was selected by the treating physician, will accompany each of the study participants will be opened and the patient identified as belonging to either Group 1 or Group 2. It is important to note that randomization of the envelopes were computer-generated and placed by a co-investigator; the treating physician is completely unaware of the order of the opaque envelopes. Patients in Group 1 will receive a standardized medication regimen including non-liposomal bupivacaine by soft-tissue injection at the conclusion of their surgical procedure. Those in Group 2 will receive non-liposomal bupivacaine and ExparelTM by soft-tissue injection at the conclusion of their surgical procedure. Study participants will undergo injection in this manner until the conclusion of the study.
Experimental: Experimental- Exparel; Group 2 will receive a mixture of non-liposomal bupivacaine and Exparel introduced into the soft tissue surrounding the fracture at the conclusion of the surgery.	Drug: Bupivacaine/Exparel; The opaque envelope, which was selected by the treating physician, will accompany each of the study participants will be opened and the patient identified as belonging to either Group 1 or Group 2. It is important to note that randomization of the envelopes were computer-generated and placed by a co-investigator; the treating physician is completely unaware of the order of the opaque envelopes. Patients in Group 1 will receive a standardized medication regimen including non-liposomal bupivacaine by soft-tissue injection at the conclusion of their surgical procedure. Those in Group 2 will receive non-liposomal bupivacaine and ExparelTM by soft-tissue injection at the conclusion of their surgical procedure. Study participants will undergo injection in this manner until the conclusion of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain Visual Analogue Scale (VAS)	Patients will be asked to complete a Pain Visual Analogue Scale every 2 hours for the first 12 hours of their stay (2, 4, 6, 8, 10, 12), and then again at 24, 30 and 72 hours into their hospitalization.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Management Satisfaction	Patients will complete the post-surgery satisfaction form at their 2-week, post-operative office visit.	2 weeks, post-operatively

Collaborators and Investigators

• Sponsor: Broward Health
• Investigators: Principal Investigator: Brian J Cross, MD, Broward Health

Publications and helpful links

General Publications

• References 1-Candoitti 2012 2-Gupta Curr Opin Anaesthesiol 2010, Liu J Am Coll Surg 2006 3-Lynch Anesth Analg 1997, Amin J Surg Pakistan 2010 4-Golf Adv Ther 2011, Onel 2011, Bergese IARS Annual Meeting 2011 5-Angst Clin Pharmacokinet 2006, Howell Cancer J 2001

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): September 1, 2015
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: August 8, 2014
• First Submitted That Met QC Criteria: August 11, 2014
• First Posted (Estimate): August 12, 2014

Study Record Updates

• Last Update Posted (Estimate): February 19, 2016
• Last Update Submitted That Met QC Criteria: February 18, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Bupivacaine; exparel; internal fixation; multimodal; open reduction; post-surgical pain control
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Wounds and Injuries; Pain, Postoperative; Fractures, Bone; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 5187