## Protocol Section
### Identification Module
**NCT ID:** NCT02341079

**Brief Title:** Intraoperative Liposomal Bupivacaine Injection in Primary Total Knee Arthroplasty

**Official Title:** Prospective Randomized Trial Comparing Intraoperative Liposomal Bupivacaine Injection With Indwelling Femoral Nerve Blockade in Early Postoperative Pain Control for Primary Total Knee Arthroplasty

#### Organization Study ID Info
**ID:** NMCSD.2014.0101
#### Organization
**Class:** FED
**Full Name:** United States Naval Medical Center, San Diego
### Status Module
#### Completion Date
**Date:** 2015-10

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2017-03-10

**Type:** ACTUAL

**Last Update Submit Date:** 2017-03-07

**Overall Status:** WITHDRAWN

#### Primary Completion Date
**Date:** 2015-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2015-03

**Status Verified Date:** 2017-03

#### Study First Post Date
**Date:** 2015-01-19
**Type:** ESTIMATED
**Study First Submit Date:** 2015-01-14
**Study First Submit QC Date:** 2015-01-16
**Why Stopped:** Principal no longer interested in conducting study
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** FED

**Name:** United States Naval Medical Center, San Diego

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of the study is to evaluate the efficacy of local infiltration of liposomal bupivacaine versus use of an indwelling femoral peripheral nerve block in controlling early postoperative pain in primary total knee arthroplasty. The investigators hope to demonstrate equivalency of treatment modalities to provide an alternative to the commonly used treatment of femoral nerve blockade.

**Detailed Description:** Postoperative pain control in total knee arthroplasty is generally managed by a multimodal approach of premedication, epidural and/or peripheral nerve blocks, narcotic medications, and anti-inflammatories. Multiple studies have evaluated the efficacy of anesthetic "cocktails" of various medications for local tissue infiltration to aide in controlling postoperative pain. A recent systematic review supported the use of local anesthetic infiltration in a single intraoperative dose as an adjunct to femoral nerve block in the relief of pain; with combinations of ropivacaine, ketorolac, and adrenaline providing the best results. Several studies noted decreases in opioid consumption and overall pain scores in the perioperative period.

A novel compound, liposomal bupivacaine (EXPAREL®, Pacira Pharmaceuticals, Inc., Parsippany, NJ, USA), has been proposed for use in total knee arthroplasty. To our knowledge, only one randomized controlled trial involving use of this compound in total knee arthroplasty has been published and was performed as a phase two dose ranging trial comparing liposomal bupivacaine to bupivacaine HCl. No statistically significant difference between the two compounds was shown, but a trend towards benefit in short term pain control was shown with EXPAREL 532mg.

Our current pain management regimen utilizes the multimodal approach of neuraxial anesthesia, indwelling femoral nerve catheter, opioids, and anti-inflammatory medications. The regional anesthesia service manages postoperative pain while the indwelling femoral nerve catheter is in place. The epidural is utilized for early postoperative analgesia and thromboprophylaxis. The epidural is discontinued on post-operative day 1 and the femoral nerve catheter is removed by the morning of postoperative day 3. Although femoral nerve catheters provide excellent pain control following TKA, there are associated disadvantages. Most notably there is inherent quadriceps weakness which places the patient at increased fall risk. To reduce the risk of falling, patients must wear a knee immobilizer with ambulation until the catheter is removed and quadriceps function has returned. This may delay the ability to actively participate in physical therapy.

The purpose of our present study is to evaluate the efficacy of local infiltration of liposomal bupivacaine versus use of an indwelling femoral peripheral nerve block in controlling early postoperative pain. The investigators aim to show equivalency between the two treatment modalities. Our hypothesis is that a systematic local infiltration of liposomal bupivacaine provided intraoperatively is equally efficacious as femoral indwelling peripheral nerve blockade in immediate postoperative pain control with more rapid progression with physical therapy.

### Conditions Module

**Conditions:**

- Osteoarthritis

- Osteoarthritis, Knee

- Arthritis, Degenerative

- Osteoarthrosis

- Osteoarthrosis Deformans

**Keywords:**

- Total Knee Arthroplasty

- Osteoarthritis

- Femoral Nerve Blockade

- Liposomal Bupivacaine

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Type:** ACTUAL

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Femoral nerve block delivered via indwelling femoral nerve catheter

**Intervention Names:**

- Drug: Indwelling femoral nerve block

**Label:** Femoral Nerve Blockade

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Intraoperative intracapsular injection of bupivacaine liposome

**Intervention Names:**

- Drug: Bupivacaine Liposome Injection

**Label:** Bupivacaine Liposome Injection

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Bupivacaine Liposome Injection

**Description:** Intraoperative intracapsular injection of 266mg of bupivacaine liposome injection diluted to 60mL with 0.9% normal saline.

**Name:** Bupivacaine Liposome Injection

**Other Names:**

- EXPAREL

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Femoral Nerve Blockade

**Description:** Femoral nerve block delivered via indwelling femoral nerve catheter with 0.125% bupivacaine.

**Name:** Indwelling femoral nerve block

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 10cm VAS scale completed by the patient at set intervals postoperatively

**Measure:** Visual Analog Pain Scale

**Time Frame:** 0-3 months

**Description:** Oral and intravenous opioid use calculated in terms of morphine equivalents

**Measure:** Oral and Intravenous Opioid Consumption

**Time Frame:** 0-5 days (during hospitalization)

**Description:** Standardized functional clinical score for knee symptoms

**Measure:** Hospital for Special Surgery (HSS) Knee Scores

**Time Frame:** 0-3 months

#### Secondary Outcomes

**Measure:** Length of Hospital Stay

**Time Frame:** 0-5 days

**Measure:** Distance ambulated with physical therapy

**Time Frame:** 0-5 days (during hospitalization)

**Description:** Time to return of quadriceps function

**Measure:** Time to straight leg raise with physical therapy

**Time Frame:** 0-5 days (during hospitalization)

**Description:** Knee range of motion measure by physical therapy and in clinic

**Measure:** Postoperative range of motion

**Time Frame:** 0-3 months

**Description:** All intervention related complications for each arm of the study

**Measure:** Postoperative complication rate

**Time Frame:** 0-3 months

**Description:** Plasma levels of bupivacaine monitored throughout hospital stay

**Measure:** Plasma bupivacaine concentrations

**Time Frame:** 0-5 days (during hospitalization)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Age over 18 years old
* Undergoing unilateral primary total knee arthroplasty

Exclusion Criteria:

* Revision total knee arthroplasty
* Bilateral total knee arthroplasty
* Prior allergy or adverse reaction to local anesthetic
* Hepatic dysfunction

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** San Diego

**Country:** United States

**Facility:** Naval Medical Center San Diego

**State:** California

**Zip:** 92134

#### Overall Officials

**Official 1:**

**Affiliation:** Naval Medical Center San Diego Department of Orthopadic Surgery

**Name:** Patrick B Morrissey, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001168

- Term: Arthritis

- ID: D000007592

- Term: Joint Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000012216

- Term: Rheumatic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

### Condition Browse Module - Browse Leaves

- ID: M12926

- Name: Osteoarthritis

- Relevance: HIGH

- As Found: Osteoarthritis

- ID: M22168

- Name: Osteoarthritis, Knee

- Relevance: HIGH

- As Found: Osteoarthritis, Knee

- ID: M13069

- Name: Pain, Postoperative

- Relevance: LOW

- As Found: Unknown

- ID: M13066

- Name: Pain

- Relevance: LOW

- As Found: Unknown

- ID: M4476

- Name: Arthritis

- Relevance: LOW

- As Found: Unknown

- ID: M10621

- Name: Joint Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15045

- Name: Rheumatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6323

- Name: Collagen Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010003

- Term: Osteoarthritis

- ID: D000020370

- Term: Osteoarthritis, Knee

### Intervention Browse Module - Ancestors

- ID: D000000779

- Term: Anesthetics, Local

- ID: D000000777

- Term: Anesthetics

- ID: D000002492

- Term: Central Nervous System Depressants

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

### Intervention Browse Module - Browse Branches

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M5315

- Name: Bupivacaine

- Relevance: HIGH

- As Found: Following

- ID: M4107

- Name: Anesthetics

- Relevance: LOW

- As Found: Unknown

- ID: M4109

- Name: Anesthetics, Local

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000002045

- Term: Bupivacaine

### Misc Info Module

- Version Holder: 2024-05-24
