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Bupivacaine Effectiveness and Safety in SABER® Trial (BESST)

Primary Purpose

Postoperative Pain, Abdominal Surgery

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
SABER-Bupivacaine
Bupivacaine HCl
SABER-Placebo
Sponsored by
Durect
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postoperative Pain focused on measuring Postoperative pain, Post-operative pain, Opioid, Laparoscopic surgery, Bupivacaine, Local anesthetic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must be able to read and understand the consent form, provide written consent, complete trial-related procedures, and communicate with the trial staff
  • Males and females, 18 years of age and older scheduled to undergo elective general abdominal surgery
  • Patients must be healthy or have only mild systemic disease
  • BMI < 45
  • Patients must have ECG wave form within normal limits
  • Female and male patients must agree to use medically acceptable method of contraception throughout the entire trial period and for 1 week after the trial participation is completed

Exclusion Criteria:

  • Patients who are pregnant or lactating
  • Patients undergoing emergency surgery (unless full consent is obtained and all screening procedures are completed prior to surgery)
  • Significant concomitant surgical procedure
  • History of multiple prior laparotomy procedures
  • Cancer with known metastases pre-operatively, which are suspected to impact post-operative recovery or pain
  • Planned formation of stoma during surgery or plans to undergo another laparotomy procedure within 30 days post-operatively
  • Pre-operative evidence of sepsis or septic shock
  • Pre-operative evaluation that suggests a surgery may preclude full closure of the incision(s)
  • Patients with current or regular use of systemic steroids, anticonvulsants, antiepileptics, antidepressants, or monoamine oxidase inhibitors, who cannot be withdrawn from these medications
  • Patients with current or regular use of drugs known to significantly prolong the QTc interval
  • Patients with known hypersensitivity to local anesthetic agents of the amide type (e.g. lidocaine, bupivacaine)
  • Patients with known hypersensitivity to morphine
  • Patients with conditions contraindicated for use of opioids
  • Patients with atrial fibrillation/flutter or other non-sinus rhythm (including paced rhythm); left bundle branch block (LBBB); or the following conditions: right bundle branch block (RBBB) in presence of a cardiac disease, significant cardiomyopathy, and myocardial infarction within last 6 months
  • Patients with a serum creatinine level two times more than the local laboratory normal limit
  • Patients who have received greater than 600 mg morphine equivalent daily dose for three or more days per week in the month prior to the surgical procedure
  • Patients who are currently being treated with methadone, or history of methadone use within the previous 6 months
  • Patients with known or suspected abuse of opioids or other illicit drugs
  • Patients with known or suspected alcohol abuse
  • Participation in another clinical trial at the same time or within 30 days of this trial
  • Patients who, in the Investigator's opinion, should not participate in the trial or may not be capable of following the trial schedule for any reason

Sites / Locations

  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site
  • DURECT Study Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Active: SABER-Bupivacaine

Comparator: Bupivacaine HCl

Placebo: SABER-Placebo

Arm Description

SABER-Bupivacaine

Bupivacaine HCl

SABER-Placebo

Outcomes

Primary Outcome Measures

Mean Pain Intensity on Movement
Mean pain intensity on movement AUC (time-normalized AUC) during the period 0 to 72 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.
Supplemental Opioid Use
Total morphine-equivalent dose during 0-72 hours post dose. Median values were presented because data was not normally distributed.

Secondary Outcome Measures

Mean Pain Intensity on Movement
Mean pain intensity on movement AUC (time-normalized AUC) during the period 0 to 48 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.
Total Morphine-equivalent Dose
Total morphine-equivalent dose during 0-48 hours post dose.
Proportion (Percent) of Patients Who Have Evidence of a Wound Infection
From Surgical Wound Healing and Local Tissue Condition Evaluation
Time-to-first Use of Opioid Rescue Medication
Number (Incidence) of Participants With Opioid-related Side Effects
AEs include: nausea, vomiting, constipation, dizziness, somnolence, urinary retention, respiratory depression
Pain Intensity at Rest AUC During 0-72 Hours Post Dose
Mean pain intensity at rest AUC during the period 0 to 72 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.
Mean Pain Intensity at Rest AUC During 0-48 Hours Post Dose
Mean pain intensity at rest AUC during the period 0 to 48 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.

Full Information

First Posted
January 18, 2010
Last Updated
May 6, 2021
Sponsor
Durect
Collaborators
Nycomed, Hospira, now a wholly owned subsidiary of Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01052012
Brief Title
Bupivacaine Effectiveness and Safety in SABER® Trial
Acronym
BESST
Official Title
Bupivacaine Effectiveness and Safety in SABER Trial (BESST)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Durect
Collaborators
Nycomed, Hospira, now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a research study testing SABER-Bupivacaine (an experimental pain-relieving medication). SABER-Bupivacaine is designed to continuously deliver bupivacaine, a common local anesthetic, for a few days in order to treat local post-surgical pain. The purpose of this study is to investigate safety (side effects) associated with the use of SABER-Bupivacaine and how well it works in reducing pain and opioid-related side effects following various kinds of abdominal surgeries.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Pain, Abdominal Surgery
Keywords
Postoperative pain, Post-operative pain, Opioid, Laparoscopic surgery, Bupivacaine, Local anesthetic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
331 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active: SABER-Bupivacaine
Arm Type
Experimental
Arm Description
SABER-Bupivacaine
Arm Title
Comparator: Bupivacaine HCl
Arm Type
Active Comparator
Arm Description
Bupivacaine HCl
Arm Title
Placebo: SABER-Placebo
Arm Type
Placebo Comparator
Arm Description
SABER-Placebo
Intervention Type
Drug
Intervention Name(s)
SABER-Bupivacaine
Other Intervention Name(s)
POSIMIR® bupivacaine solution
Intervention Description
Injectable Extended Release Solution; SABER-Bupivacaine /Once
Intervention Type
Drug
Intervention Name(s)
Bupivacaine HCl
Intervention Description
Injectable Solution; Bupivacaine HCl /Once
Intervention Type
Drug
Intervention Name(s)
SABER-Placebo
Intervention Description
Injectable Solution; SABER-Placebo/Once
Primary Outcome Measure Information:
Title
Mean Pain Intensity on Movement
Description
Mean pain intensity on movement AUC (time-normalized AUC) during the period 0 to 72 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.
Time Frame
0 to 72 hours post-dose
Title
Supplemental Opioid Use
Description
Total morphine-equivalent dose during 0-72 hours post dose. Median values were presented because data was not normally distributed.
Time Frame
0-72 hours post dose
Secondary Outcome Measure Information:
Title
Mean Pain Intensity on Movement
Description
Mean pain intensity on movement AUC (time-normalized AUC) during the period 0 to 48 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.
Time Frame
0 to 48 hours post-dose
Title
Total Morphine-equivalent Dose
Description
Total morphine-equivalent dose during 0-48 hours post dose.
Time Frame
0-48 hours post dose
Title
Proportion (Percent) of Patients Who Have Evidence of a Wound Infection
Description
From Surgical Wound Healing and Local Tissue Condition Evaluation
Time Frame
0 to 14 days post-dose (Visits 3 and 4)
Title
Time-to-first Use of Opioid Rescue Medication
Time Frame
0 to 14 days post-dose (Time from extubation until first opioid use)
Title
Number (Incidence) of Participants With Opioid-related Side Effects
Description
AEs include: nausea, vomiting, constipation, dizziness, somnolence, urinary retention, respiratory depression
Time Frame
0 to 30 days post-dose
Title
Pain Intensity at Rest AUC During 0-72 Hours Post Dose
Description
Mean pain intensity at rest AUC during the period 0 to 72 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.
Time Frame
0-72 hours post dose
Title
Mean Pain Intensity at Rest AUC During 0-48 Hours Post Dose
Description
Mean pain intensity at rest AUC during the period 0 to 48 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude.
Time Frame
0-48 hours post dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must be able to read and understand the consent form, provide written consent, complete trial-related procedures, and communicate with the trial staff Males and females, 18 years of age and older scheduled to undergo elective general abdominal surgery Patients must be healthy or have only mild systemic disease BMI < 45 Patients must have ECG wave form within normal limits Female and male patients must agree to use medically acceptable method of contraception throughout the entire trial period and for 1 week after the trial participation is completed Exclusion Criteria: Patients who are pregnant or lactating Patients undergoing emergency surgery (unless full consent is obtained and all screening procedures are completed prior to surgery) Significant concomitant surgical procedure History of multiple prior laparotomy procedures Cancer with known metastases pre-operatively, which are suspected to impact post-operative recovery or pain Planned formation of stoma during surgery or plans to undergo another laparotomy procedure within 30 days post-operatively Pre-operative evidence of sepsis or septic shock Pre-operative evaluation that suggests a surgery may preclude full closure of the incision(s) Patients with current or regular use of systemic steroids, anticonvulsants, antiepileptics, antidepressants, or monoamine oxidase inhibitors, who cannot be withdrawn from these medications Patients with current or regular use of drugs known to significantly prolong the QTc interval Patients with known hypersensitivity to local anesthetic agents of the amide type (e.g. lidocaine, bupivacaine) Patients with known hypersensitivity to morphine Patients with conditions contraindicated for use of opioids Patients with atrial fibrillation/flutter or other non-sinus rhythm (including paced rhythm); left bundle branch block (LBBB); or the following conditions: right bundle branch block (RBBB) in presence of a cardiac disease, significant cardiomyopathy, and myocardial infarction within last 6 months Patients with a serum creatinine level two times more than the local laboratory normal limit Patients who have received greater than 600 mg morphine equivalent daily dose for three or more days per week in the month prior to the surgical procedure Patients who are currently being treated with methadone, or history of methadone use within the previous 6 months Patients with known or suspected abuse of opioids or other illicit drugs Patients with known or suspected alcohol abuse Participation in another clinical trial at the same time or within 30 days of this trial Patients who, in the Investigator's opinion, should not participate in the trial or may not be capable of following the trial schedule for any reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dmitri Lissin, MD
Organizational Affiliation
Durect
Official's Role
Study Director
Facility Information:
Facility Name
DURECT Study Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
DURECT Study Site
City
Florence
State/Province
Alabama
ZIP/Postal Code
35630
Country
United States
Facility Name
DURECT Study Site
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
DURECT Study Site
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36617
Country
United States
Facility Name
DURECT Study Site
City
Montgomery
State/Province
Alabama
ZIP/Postal Code
36106
Country
United States
Facility Name
DURECT Study Site
City
Sheffield
State/Province
Alabama
ZIP/Postal Code
35660
Country
United States
Facility Name
DURECT Study Site
City
Arcadia
State/Province
California
ZIP/Postal Code
91007
Country
United States
Facility Name
DURECT Study Site
City
Fontana
State/Province
California
ZIP/Postal Code
92335
Country
United States
Facility Name
DURECT Study Site
City
Laguna Hills
State/Province
California
ZIP/Postal Code
92653
Country
United States
Facility Name
DURECT Study Site
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
DURECT Study Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
DURECT Study Site
City
Powder Springs
State/Province
Georgia
ZIP/Postal Code
30127
Country
United States
Facility Name
DURECT Study Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46206
Country
United States
Facility Name
DURECT Study Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02135
Country
United States
Facility Name
DURECT Study Site
City
Troy
State/Province
Michigan
ZIP/Postal Code
48085
Country
United States
Facility Name
DURECT Study Site
City
Duluth
State/Province
Minnesota
ZIP/Postal Code
55805
Country
United States
Facility Name
DURECT Study Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
DURECT Study Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
DURECT Study Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
DURECT Study Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
DURECT Study Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
DURECT Study Site
City
Temple
State/Province
Texas
ZIP/Postal Code
77375
Country
United States
Facility Name
DURECT Study Site
City
Woodville South
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Facility Name
DURECT Study Site
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
DURECT Study Site
City
Ringwood East
State/Province
Victoria
ZIP/Postal Code
3135
Country
Australia
Facility Name
DURECT Study Site
City
Christchurch
ZIP/Postal Code
8022
Country
New Zealand

12. IPD Sharing Statement

Learn more about this trial

Bupivacaine Effectiveness and Safety in SABER® Trial

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