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TerminatedNCT02058290IMPROVE-LapUpdated May 14, 2014Results posted

A Health Economic Trial in Adult Patients Undergoing Laparoscopic Colectomy

A Phase 4 interventional study of IV morphine sulfate or Sponsor-approved equivalent and EXPAREL in Bowel Obstruction, sponsored by Pacira Pharmaceuticals, Inc. Terminated at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-05-14.

Sponsored by Pacira Pharmaceuticals, Inc · Phase 4, Interventional, and Health services research

Why this study was terminated
Slower than expected enrollment
Phase
Phase 4
Study type
Interventional
Enrollment
122
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
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Study summary

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.

Read the 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.

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Conditions studied

  • Bowel Obstruction

Keywords

  • laparoscopic colectomy
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In context

Intestinal Obstruction

160 studies on the registry are indexed under Intestinal Obstruction; 27 are open to participants now.

This study's enrollment of 122 is above the median of 80 across 80 interventional studies indexed under Intestinal Obstruction.

Browse Intestinal Obstruction studies →

Lead sponsor

Pacira Pharmaceuticals, Inc is the lead sponsor of 100 studies on the registry; 3 are open to participants now.

Of its 26 completed or terminated interventional studies of FDA-regulated products, 17 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 4
Primary purpose
Health services research
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
122 participants (actual)

Study arms

  • Active comparator
    IV Morphine Sulfate or Sponsor-approved Equivalent

    Standard of Care (SOC)

    Drug: IV morphine sulfate or Sponsor-approved equivalent

  • Experimental
    EXPAREL

    EXPAREL (bupivacaine liposome injectable suspension)

    Drug: EXPAREL

Interventions

  • DrugIV 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.

  • DrugEXPAREL

    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.

    Also known as: bupivacaine liposome injectable suspension

06

What researchers measure

Primary outcomes

  1. Total Opioid Burden

    Total opioid consumed (IV and PO) postsurgically until hospital discharge order is written or through Day 30, whichever is sooner.

    Time frame: Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.

  2. 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.

    Time frame: Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.

  3. 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.

    Time frame: Wound closure at time hospital discharge order is written or Day 30, whichever is sooner

Secondary outcomes

  1. 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.

    Time frame: Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.

  2. Patient Satisfaction With Pain Treatment After Surgery

    Responses to question pertaining to patient satisfaction with pain treatment

    Time frame: Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.

07

Results

Posted May 14, 2014

Participant flow

Participant flow — Overall Study
MilestoneIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
Started7745
Completed6636
Not completed119
Withdrew: Protocol violation21
Withdrew: Physician decision10
Withdrew: Didn't meet intraoperative criteria87
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryTotal Opioid Burden

Total opioid consumed (IV and PO) postsurgically until hospital discharge order is written or through Day 30, whichever is sooner.

Time frame:
Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.
Reported as:
Mean · mg
Total Opioid Burden
mgIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
Total Opioid Burden96.47 ± 77.7432.06 ± 53.16
Statistical analysis
  • IV Morphine Sulfate or Sponsor-approved Equivalent vs EXPAREL · ANOVA · p = <0.0001
PrimaryHealth 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.

Time frame:
Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.
Reported as:
Mean · dollars
Health Economic Benefits - Total Cost of Hospitalization
dollarsIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
Health Economic Benefits - Total Cost of Hospitalization15158.79 ± 11417.5014802.70 ± 18382.12
Statistical analysis
  • IV Morphine Sulfate or Sponsor-approved Equivalent vs EXPAREL · ANOVA · p = 0.2612
PrimaryHealth 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.

Time frame:
Wound closure at time hospital discharge order is written or Day 30, whichever is sooner
Reported as:
Median · days
Health Economic Benefits - Length of Stay (LOS)
daysIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
Health Economic Benefits - Length of Stay (LOS)4.0 (0 to 30)3.0 (1.9 to 10.7)
Statistical analysis
  • IV Morphine Sulfate or Sponsor-approved Equivalent vs EXPAREL · Log Rank · p = 0.0019
SecondaryIncidence 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.

Time frame:
Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.
Reported as:
Number · participants
Incidence of Opioid-related Adverse Events
participantsIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
Incidence of Opioid-related Adverse Events232
SecondaryPatient Satisfaction With Pain Treatment After Surgery

Responses to question pertaining to patient satisfaction with pain treatment

Time frame:
Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.
Reported as:
Number · participants
Patient Satisfaction With Pain Treatment After Surgery
participantsIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
Extremely Satisfied3017
Satisfied195
Neither Satisfied nor Dissatisfied02
Dissatisfied30
Extremely Dissatisfied10
Not Reported32

Adverse events

Collected over Through Day 30 post surgery.. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
IV Morphine Sulfate or Sponsor-approved Equivalent—9/67 (13.4%)53/67 (79.1%)
EXPAREL—5/38 (13.2%)15/38 (39.5%)
Most frequent serious events
Showing 10 of 27
Most frequent serious events
EventIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
Small Intestinal ObstructionGastrointestinal disorders2/670/38
Urinary Tract InfectionInfections and infestations2/670/38
Abdominal painGastrointestinal disorders1/671/38
Gastrointestinal PerforationGastrointestinal disorders0/671/38
Intestinal PerforationGastrointestinal disorders0/671/38
Cholecystitis AcuteHepatobiliary disorders0/671/38
AbscessInfections and infestations0/671/38
Bacterial InfectionInfections and infestations0/671/38
Bacterial SepsisInfections and infestations0/671/38
Wound InfectionInfections and infestations0/671/38
Most frequent other events
Showing 10 of 29
Most frequent other events
EventIV Morphine Sulfate or Sponsor-approved EquivalentEXPAREL
NauseaGastrointestinal disorders23/673/38
HeadacheNervous system disorders7/670/38
Abdominal DistentionGastrointestinal disorders5/670/38
Abdominal PainGastrointestinal disorders5/672/38
VomitingGastrointestinal disorders5/670/38
Urinary RetentionRenal and urinary disorders5/670/38
PruritusSkin and subcutaneous tissue disorders5/670/38
AnemiaBlood and lymphatic system disorders4/672/38
LeukocytosisBlood and lymphatic system disorders4/670/38
Urinary Tract InfectionInfections and infestations4/670/38

Baseline characteristics

122 subjects were enrolled. Of these, 105 subjects received study drug: 67 subjects received IV morphine sulfate or sponsor-approved equivalent and 38 subjects received EXPAREL.

Age, Continuous
Age, Continuous(years)IV Morphine Sulfate or Sponsor-approved EquivalentEXPARELTotal
Mean58.6 ± 14.3557.8 ± 11.8658.3 ± 13.45
Sex: Female, Male
Sex: Female, Male(Participants)IV Morphine Sulfate or Sponsor-approved EquivalentEXPARELTotal
Female352156
Male321749
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)IV Morphine Sulfate or Sponsor-approved EquivalentEXPARELTotal
Hispanic or Latino7411
Not Hispanic or Latino603494
American Society of Anesthesiologist (ASA) Classification
American Society of Anesthesiologist (ASA) Classification(participants)IV Morphine Sulfate or Sponsor-approved EquivalentEXPARELTotal
Normal [1]101
Mild Systemic Disease [2]322557
Severe Systemic Disease [3]321345
Severe Systemic Disease Threat to Life [4]202
Patient's Pain Level 24 Hours Prior to Surgery
Patient's Pain Level 24 Hours Prior to Surgery(units on a scale)IV Morphine Sulfate or Sponsor-approved EquivalentEXPARELTotal
Mean1.9 ± 2.141.3 ± 0.861.7 ± 1.81
08

Study locations

6 sites
  • Washington Hospital Center
    Washington DC, District of Columbia 20010, United States
  • University of Miami, Dept. Anesthesiology
    Miami, Florida 33136, United States
  • Tampa General Hospital
    Tampa, Florida 33606, United States
  • Albany Medical College
    Albany, New York 12208, United States
  • The Ohio State University Medical Center
    Columbus, Ohio 43210, United States
  • Methodist Hospital
    Houston, Texas 77030, United States
09

References and documents

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. PubMed 25018650 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 14, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02058290
Lead sponsor
Pacira Pharmaceuticals, Inc
Collaborators
Registrat-Mapi
Responsible party
Sponsor
First posted
Feb 10, 2014
Start date
Dec 2011
Primary completion
Sep 2012
Completion
Feb 2013
Results posted
May 14, 2014
Last update
May 14, 2014

Study contacts

Edward C Lee, MD
principal investigator · Albany Medical College
Keith Candiotti, MD
principal investigator · University of Miami
Sergio Bergese, MD
principal investigator · Ohio State University
Eric M Haas, MD
principal investigator · The Methodist Hospital Research Institute
Jorge Marcet, MD
principal investigator · Tampa General Hospital
Anjali Kumar, MD
principal investigator · Medstar Health Research Institute

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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