A Health Economic Trial in Adult Patients Undergoing Laparoscopic Colectomy (IMPROVE-Lap)

A Pain Relief Trial Utilizing the Infiltration of a Multivesicular Liposome Formulation of Bupivacaine, EXPAREL(R): A Phase 4 Health Economic Trial in Adult Patients Undergoing Laparoscopic Colectomy (IMPROVE-Lap Colectomy)

This study is designed to compare the standard of care against EXPAREL (bupivacaine liposome injectable suspension) to determine if total opioid consumption is reduced when using EXPAREL, therefore possibly reducing total hospital costs.

Study Overview

• Status: Terminated
• Conditions: Bowel Obstruction
• Intervention / Treatment: Drug: IV morphine sulfate or Sponsor-approved equivalent; Drug: EXPAREL

Detailed Description

This is a Phase 4, prospective, sequential, open-label study designed to evaluate the efficacy, safety, and health economic benefits of intraoperative local wound infiltration with EXPAREL (bupivacaine liposome injectable suspension) compared with postsurgical administration of standardized intravenous (IV) morphine sulfate or Sponsor-approved equivalent for postsurgical analgesia in adult patients undergoing laparoscopic colectomy with general anesthesia.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington DC, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Dept. Anesthesiology
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Methodist Hospital

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:

• Male or female, at least 18 years of age.
• Patients scheduled to undergo laparoscopic segmental colectomy with planned primary anastamosis, as defined by cecectomy, right hemicolectomy, resection of transverse colon, left hemicolectomy, or sigmoidectomy. (Note: patients who converted from a planned laparoscopic colectomy to an open colectomy were not eligible.)
• Ability to provide informed consent, adhere to study visit schedule, and complete all study assessments.

Exclusion Criteria:

• Patients with a history of hypersensitivity or idiosyncratic reactions or intolerance to any local anesthetic, opioid, or propofol.
• Patients who abuse alcohol or other drug substance.
• Patients with severe hepatic impairment.
• Patients currently pregnant or who may become pregnant during the course of the study or who are unwilling to use acceptable means of contraception for at least 1 month before and 1 month after dosing. Acceptable means of contraception include hormonal contraceptives (e.g., oral, injectable, implantable), effective barrier methods (e.g., condoms with spermicide), intrauterine device, lifestyle with a personal choice of abstinence, non-heterosexual lifestyle, or in a strictly monogamous relationship with a partner who has had a vasectomy.
• Patients with any psychiatric, psychological, or other condition that the Investigator feels may make the patient an inappropriate candidate for this clinical study.
• Participation in an EXPAREL study within the last 30 days.
• Patients who have received any investigational drug within 30 days prior to study drug administration, or planned administration of another investigational product or procedure during the patient's participation in this study.

In addition, a patient was ineligible if he or she met the following criteria during surgery:

• Patients who had any concurrent surgical procedure.
• Patients with unplanned multiple segmental resections of large intestine.
• Patients who converted from laparoscopic-assisted colectomy to traditional open colectomy.
• Patients who had unplanned, temporary or permanent colostomies, ileostomies, or the like placed.
• Patients who received intraoperative administration of opioids (other than fentanyl or analogs) or any other analgesic, local anesthetics, or anti-inflammatory agents.
• Patients who received Entereg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IV Morphine Sulfate or Sponsor-approved Equivalent; Standard of Care (SOC)	Drug: IV morphine sulfate or Sponsor-approved equivalent; Patients in this group will receive IV morphine sulfate or Sponsor-approved equivalent via a patient-controlled analgesia (PCA) pump, as needed. The PCA pump will be set up postsurgically as soon as possible and prior to the patient leaving the post-anesthesia care unit (PACU) or immediately upon transfer to a floor if the stay in the PACU is less than one hour.
Experimental: EXPAREL; EXPAREL (bupivacaine liposome injectable suspension)	Drug: EXPAREL; Patients will receive 266 mg EXPAREL diluted with preservative-free 0.9% normal saline to a total volume of 40 cc administered via wound infiltration prior to wound closure. When not contraindicated, 30 mg IV ketorolac will be given at the end of surgery. If not indicated, an IV non-steroidal anti-inflammatory drug (NSAID) may be substituted per the site's standard of care. All patients will be offered rescue analgesia, as needed.; Other Names: bupivacaine liposome injectable suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Opioid Burden	Total opioid consumed (IV and PO) postsurgically until hospital discharge order is written or through Day 30, whichever is sooner.	Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.
Health Economic Benefits - Total Cost of Hospitalization	Total cost of hospitalization until the time hospital discharge order is written or through Day 30, whichever was sooner.	Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.
Health Economic Benefits - Length of Stay (LOS)	Length of stay, recorded in days, defined as the time of completion of the wound closure until the hospital discharge order is written or through Day 30, whichever is sooner.	Wound closure at time hospital discharge order is written or Day 30, whichever is sooner

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Opioid-related Adverse Events	Incidence of opioid-related adverse events defined as somnolence, respiratory depression, hypoventilation, hypoxia, dry mouth, nausea, vomiting, constipation, sedation, confusion, pruritus, urinary retention, and postoperative ileus.	Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.
Patient Satisfaction With Pain Treatment After Surgery	Responses to question pertaining to patient satisfaction with pain treatment	Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc
• Collaborators: Registrat-Mapi
• Investigators: Principal Investigator: Keith Candiotti, MD, University of Miami; Principal Investigator: Sergio Bergese, MD, Ohio State University; Principal Investigator: Edward C Lee, MD, Albany Medical College; Principal Investigator: Eric M Haas, MD, The Methodist Hospital Research Institute; Principal Investigator: Jorge Marcet, MD, Tampa General Hospital; Principal Investigator: Anjali Kumar, MD, MedStar Health Research Institute

Publications and helpful links

General Publications

• Cohen SM, Vogel JD, Marcet JE, Candiotti KA. Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis. J Pain Res. 2014 Jun 24;7:359-66. doi: 10.2147/JPR.S63764. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 10, 2014

Study Record Updates

• Last Update Posted (Estimate): May 14, 2014
• Last Update Submitted That Met QC Criteria: April 15, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: laparoscopic colectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bupivacaine; Morphine
• Other Study ID Numbers: MA402S23B6A/6B