Postoperative Pain
Conditions
Keywords
Post operative pain, Local anaesthesia, Postoperative pain after arthroscopic shoulder surgery
Brief summary
The objective is to identify the optimal dose of SABER-Bupivacaine for postoperative pain control in patients undergoing elective arthroscopic shoulder surgery on the basis of pharmacokinetics, efficacy and safety evaluations. The study duration consists of a screening period up to 14 days and a treatment period 14 days with a long term follow up visit at 6 months. The study will provide further data on safety.
Interventions
5.0 ml
5.0 ml
20.0 ml
7.5 ml
7.5 ml
20.0 ml
Sponsors
Nycomed
Durect
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subacromial impingement syndrome * MRI with intact rotator cuff * Patients suitable for general anaesthesia
Exclusion criteria
* Known major joint trauma, infection, avascular necrosis, chronic dislocation, inflammatory or degenerative glenohumeral arthropathy, glenohumeral arthritis, frozen shoulder or previous surgery of the affected shoulder * Abnormal ECG * Prolonged QT syndrome * Current or regular use of analgesic medication for other indication(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity (PI) | 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. |
| Supplemental Opioid Use | 0-3 days after surgery | Cumulative IV morphine-equivalent dose of opioid rescue medication |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Opioid Rescue Medication Usage | 0-14 days after surgery | — |
| Opioid Related Side Effects | 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. |
Countries
Austria, Germany, Latvia, Poland, Sweden
Participant flow
Recruitment details
Multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled study in adult subjects undergoing elective arthroscopic subacromial decompression.
Participants by arm
| Arm | Count |
|---|---|
| SABER-Bupivacaine 5 mL, single dose instilled subacromially | 53 |
| SABER-placebo 5 mL, single dose instilled subacromially | 25 |
| Bupivacaine HCl 0.25% 20 mL, single dose instilled subacromially | 29 |
| Total | 107 |
Baseline characteristics
| Characteristic | SABER-Bupivacaine | SABER-placebo | Bupivacaine HCl | Total |
|---|---|---|---|---|
| Age, Continuous | 50.1 years | 48.6 years | 51.6 years | 50.2 years |
| Sex: Female, Male Female | 33 Participants | 14 Participants | 17 Participants | 64 Participants |
| Sex: Female, Male Male | 20 Participants | 11 Participants | 12 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 25 | 0 / 29 |
| other Total, other adverse events | 12 / 53 | 6 / 25 | 6 / 29 |
| serious Total, serious adverse events | 1 / 53 | 1 / 25 | 4 / 29 |
Outcome results
Primary
Pain Intensity (PI)
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.
Time frame: 0-3 days after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SABER-Bupivacaine | Pain Intensity (PI) | 5.16 score on a scale (time-normalized AUC) | Standard Deviation 1.94 |
| SABER-placebo | Pain Intensity (PI) | 6.43 score on a scale (time-normalized AUC) | Standard Deviation 1.77 |
| Bupivacaine HCl | Pain Intensity (PI) | 5.16 score on a scale (time-normalized AUC) | Standard Deviation 2.38 |
Comparison: Exploratory comparison between SABER-Bupivacaine and Bupivacaine HCl not analyzed inferentiallyp-value: 0.01295% CI: [-2.25, -0.28]t-test in ANOVA model
Primary
Supplemental Opioid Use
Cumulative IV morphine-equivalent dose of opioid rescue medication
Time frame: 0-3 days after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SABER-Bupivacaine | Supplemental Opioid Use | 4.0 mg |
| SABER-placebo | Supplemental Opioid Use | 12.0 mg |
| Bupivacaine HCl | Supplemental Opioid Use | 8.0 mg |
Comparison: Exploratory comparison between SABER-Bupivacaine and Bupivacaine HCl not analyzed inferentiallyp-value: 0.0195% CI: [-12, 0]Wilcoxon (Mann-Whitney)
Secondary
Opioid Related Side Effects
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.
Time frame: 0-7 days after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SABER-Bupivacaine | Opioid Related Side Effects | 0.22 score on a scale | Standard Deviation 0.35 |
| SABER-placebo | Opioid Related Side Effects | 0.22 score on a scale | Standard Deviation 0.24 |
| Bupivacaine HCl | Opioid Related Side Effects | 0.25 score on a scale | Standard Deviation 0.24 |
Comparison: Exploratory comparison between SABER-Bupivacaine and Bupivacaine HCl not analyzed inferentiallyp-value: 0.77395% CI: [-0.18, 0.14]ANOVA
Secondary
Time to First Opioid Rescue Medication Usage
Time frame: 0-14 days after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SABER-Bupivacaine | Time to First Opioid Rescue Medication Usage | 12.4 hours |
| SABER-placebo | Time to First Opioid Rescue Medication Usage | 1.2 hours |
| Bupivacaine HCl | Time to First Opioid Rescue Medication Usage | 1.4 hours |
Comparison: Exploratory comparison between SABER-Bupivacaine and Bupivacaine HCl not analyzed inferentiallyp-value: 0.014Log Rank