Trial Outcomes & Findings for An International Trial to Evaluate the Efficacy and Safety of SABER®-Bupivacaine for Postoperative Pain Control in Patients Following Arthroscopic Shoulder Surgery (NCT NCT00993798)

NCT ID: NCT00993798

Last Updated: 2021-06-09

Results Overview

Mean pain intensity on movement AUC (time-normalized AUC) during the period 0-3 days after surgery. 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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

107 participants

Primary outcome timeframe

0-3 days after surgery

Results posted on

2021-06-09

Participant Flow

Multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled study in adult subjects undergoing elective arthroscopic subacromial decompression.

Participant milestones

Participant milestones
Measure
SABER-Bupivacaine 5 mL
5 mL, single dose instilled subacromially
SABER-placebo 5 mL
5 mL, single dose instilled subacromially
Bupivacaine HCl 0.25% 20 mL
0.25% 20 mL, single dose instilled subacromially
SABER- Placebo 7.5 mL
7.5 mL, single dose instilled subacromially. This arm was never pursued.
SABER-Bupivacaine 7.5 mL
7.5 mL, single dose instilled subacromially. This arm was never pursued.
Overall Study
STARTED
53
25
29
0
0
Overall Study
COMPLETED
53
25
29
0
0
Overall Study
NOT COMPLETED
0
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An International Trial to Evaluate the Efficacy and Safety of SABER®-Bupivacaine for Postoperative Pain Control in Patients Following Arthroscopic Shoulder Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SABER-Bupivacaine
n=53 Participants
5 mL, single dose instilled subacromially
SABER-placebo
n=25 Participants
5 mL, single dose instilled subacromially
Bupivacaine HCl
n=29 Participants
0.25% 20 mL, single dose instilled subacromially
Total
n=107 Participants
Total of all reporting groups
Age, Continuous
50.1 years
n=5 Participants
48.6 years
n=7 Participants
51.6 years
n=5 Participants
50.2 years
n=4 Participants
Sex: Female, Male
Female
33 Participants
n=5 Participants
14 Participants
n=7 Participants
17 Participants
n=5 Participants
64 Participants
n=4 Participants
Sex: Female, Male
Male
20 Participants
n=5 Participants
11 Participants
n=7 Participants
12 Participants
n=5 Participants
43 Participants
n=4 Participants

PRIMARY outcome

Timeframe: 0-3 days after surgery

Mean pain intensity on movement AUC (time-normalized AUC) during the period 0-3 days after surgery. 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.

Outcome measures

Outcome measures
Measure
SABER-Bupivacaine
n=53 Participants
5 mL, single dose instilled subacromially
SABER-placebo
n=25 Participants
5 mL, single dose instilled subacromially
Bupivacaine HCl
n=29 Participants
0.25% 20 mL, single dose instilled subacromially
Pain Intensity (PI)
5.16 score on a scale (time-normalized AUC)
Standard Deviation 1.94
6.43 score on a scale (time-normalized AUC)
Standard Deviation 1.77
5.16 score on a scale (time-normalized AUC)
Standard Deviation 2.38

PRIMARY outcome

Timeframe: 0-3 days after surgery

Cumulative IV morphine-equivalent dose of opioid rescue medication

Outcome measures

Outcome measures
Measure
SABER-Bupivacaine
n=53 Participants
5 mL, single dose instilled subacromially
SABER-placebo
n=25 Participants
5 mL, single dose instilled subacromially
Bupivacaine HCl
n=29 Participants
0.25% 20 mL, single dose instilled subacromially
Supplemental Opioid Use
4.0 mg
Interval 0.0 to 15.0
12.0 mg
Interval 4.0 to 36.0
8.0 mg
Interval 0.0 to 16.0

SECONDARY outcome

Timeframe: 0-14 days after surgery

Outcome measures

Outcome measures
Measure
SABER-Bupivacaine
n=53 Participants
5 mL, single dose instilled subacromially
SABER-placebo
n=25 Participants
5 mL, single dose instilled subacromially
Bupivacaine HCl
n=29 Participants
0.25% 20 mL, single dose instilled subacromially
Time to First Opioid Rescue Medication Usage
12.4 hours
Interval 1.2 to
The confidence interval is for a median estimated by a Kaplan-Meier curve. There were too few events overall to estimate an upper endpoint for this interval.
1.2 hours
Interval 0.7 to 1.5
1.4 hours
Interval 1.0 to 4.1

SECONDARY outcome

Timeframe: 0-7 days after surgery

Opioid-related side effects were recorded 0-7 days after surgery. The Opioid-Related Symptom Distress Scale (OR-SDS) is a composite score computed from a questionnaire containing frequent opioid-related symptoms (Fatigue, Drowsiness, Inability to concentrate, Nausea, Dizziness, Constipation, Itching, Difficulty with urination, Confusion, Retching/vomiting). For each symptom, patients assigned integer scores to assess severity (none=0 to very severe=4), bothersomeness (none=0 to very much=5), and frequency (none=0 to almost constantly=4); patients reported number of Retching/vomiting episodes (none=0, 1-2 episodes=1, 3-4 episodes=2, 5-6 episodes=3, \>6 episodes=4). On each day (Day 0-7), the score for each symptom was the mean of the three component scores, and the OR-SDS score was the overall mean of the 10 symptom scores, (values from 0 to 4; larger outcomes are worse). The mean of the daily OR-SDS score from Day 0 to 7 gave the overall OR-SDS Score.

Outcome measures

Outcome measures
Measure
SABER-Bupivacaine
n=37 Participants
5 mL, single dose instilled subacromially
SABER-placebo
n=21 Participants
5 mL, single dose instilled subacromially
Bupivacaine HCl
n=23 Participants
0.25% 20 mL, single dose instilled subacromially
Opioid Related Side Effects
0.22 score on a scale
Standard Deviation 0.35
0.22 score on a scale
Standard Deviation 0.24
0.25 score on a scale
Standard Deviation 0.24

Adverse Events

SABER-Bupivacaine

Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths

SABER-placebo

Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths

Bupivacaine HCl

Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
SABER-Bupivacaine
n=53 participants at risk
5 mL, single dose instilled subacromially
SABER-placebo
n=25 participants at risk
5 mL, single dose instilled subacromially
Bupivacaine HCl
n=29 participants at risk
0.25% 20 mL, single dose instilled subacromially
Respiratory, thoracic and mediastinal disorders
Pleurisy
0.00%
0/53
0.00%
0/25
3.4%
1/29
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension
1.9%
1/53
0.00%
0/25
0.00%
0/29
General disorders
Drug intolerance
0.00%
0/53
4.0%
1/25
0.00%
0/29
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
0.00%
0/53
0.00%
0/25
3.4%
1/29
Nervous system disorders
Tongue paralysis
0.00%
0/53
0.00%
0/25
3.4%
1/29
Pregnancy, puerperium and perinatal conditions
Pregnancy
0.00%
0/53
0.00%
0/25
3.4%
1/29

Other adverse events

Other adverse events
Measure
SABER-Bupivacaine
n=53 participants at risk
5 mL, single dose instilled subacromially
SABER-placebo
n=25 participants at risk
5 mL, single dose instilled subacromially
Bupivacaine HCl
n=29 participants at risk
0.25% 20 mL, single dose instilled subacromially
Nervous system disorders
Headache
5.7%
3/53
4.0%
1/25
3.4%
1/29
Nervous system disorders
Dizziness
0.00%
0/53
4.0%
1/25
3.4%
1/29
Nervous system disorders
Hypoaesthesia
1.9%
1/53
0.00%
0/25
3.4%
1/29
Gastrointestinal disorders
Nausea
1.9%
1/53
12.0%
3/25
3.4%
1/29
Investigations
ALT increased
1.9%
1/53
8.0%
2/25
0.00%
0/29
Investigations
ECG T wave abnormal
3.8%
2/53
0.00%
0/25
0.00%
0/29
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
3.8%
2/53
4.0%
1/25
6.9%
2/29
Cardiac disorders
Bradycardia
0.00%
0/53
4.0%
1/25
3.4%
1/29
Injury, poisoning and procedural complications
Procedural pain
3.8%
2/53
0.00%
0/25
0.00%
0/29
Skin and subcutaneous tissue disorders
Pruritus generalized
3.8%
2/53
0.00%
0/25
0.00%
0/29

Additional Information

Deborah Scott

Durect Corporation

Phone: 408-777-1417

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place