Postoperative Pain
Conditions
Keywords
Postoperative pain, Local anaesthesia, Postoperative pain after open abdominal hysterectomy surgery
Brief summary
The objective is to identify the optimal dose of SABER-Bupivacaine for postoperative pain control in patients undergoing hysterectomy 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 the efficacy and safety of the product.
Interventions
5.0 ml
5.0 ml
40 ml
7.5 ml
7.5 ml
40 ml
Sponsors
Nycomed
Durect
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A planned elective, abdominal hysterectomy * Patients suitable for general anaesthesia
Exclusion criteria
* Known clinically significant hepatic, gastrointestinal, renal, haematological, urologic, neurological, respiratory, endocrine or cardiovascular system abnormalities * Known serious uncontrolled illness: cancer, psychiatric or metabolic disturbances. History of cured localised malignancies is allowed (i.e. basal or squamous cell skin carcinoma, breast carcinoma or cervical carcinoma) * 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) | 1 to 72 hours post-surgery | Pain intensity (PI) on movement AUC over the period 1 to 72 hours post-surgery. Subjects assessed their pain intensity using an 11-point Pain Intensity Numeric Rating Scale (PI-NRS) with NRS scores ranging from 0 (no pain) to 10 (worst pain possible). 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
France, Germany, Hungary, Latvia, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SABER-Bupivacaine 5 mL, single dose instilled into surgical incision | 61 |
| SABER-placebo 5 mL, single dose instilled into surgical incision | 27 |
| Bupivacaine HCl 0.25% 40 mL, single dose infiltrated peri-incisionally | 27 |
| Total | 115 |
Baseline characteristics
| Characteristic | SABER-Bupivacaine | SABER-placebo | Bupivacaine HCl | Total |
|---|---|---|---|---|
| Age, Continuous | 46.7 years | 44.3 years | 45.1 years | 45.8 years |
| BMI | 26.1 kg/m^2 | 26.2 kg/m^2 | 27.0 kg/m^2 | 26.4 kg/m^2 |
| Sex: Female, Male Female | 61 Participants | 27 Participants | 27 Participants | 115 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 48 / 60 | 17 / 27 | 19 / 27 |
| serious Total, serious adverse events | 7 / 60 | 0 / 27 | 0 / 27 |
Outcome results
Primary
Pain Intensity (PI)
Pain intensity (PI) on movement AUC over the period 1 to 72 hours post-surgery. Subjects assessed their pain intensity using an 11-point Pain Intensity Numeric Rating Scale (PI-NRS) with NRS scores ranging from 0 (no pain) to 10 (worst pain possible). 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: 1 to 72 hours post-surgery
Population: ITT population (patients with data available)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SABER-Bupivacaine | Pain Intensity (PI) | 4.15 score on a scale | Standard Deviation 1.74 |
| SABER-placebo | Pain Intensity (PI) | 4.46 score on a scale | Standard Deviation 1.48 |
| Bupivacaine HCl | Pain Intensity (PI) | 4.27 score on a scale | Standard Deviation 1.69 |
Comparison: Exploratory comparison between SABER-Bupivacaine and Bupivacaine HCl not analyzed inferentiallyp-value: 0.46795% CI: [-0.79, 0.36]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
Population: ITT population (patients with data available)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SABER-Bupivacaine | Supplemental Opioid Use | 22.8 mg | Standard Deviation 24.3 |
| SABER-placebo | Supplemental Opioid Use | 26.3 mg | Standard Deviation 25.7 |
| Bupivacaine HCl | Supplemental Opioid Use | 23.9 mg | Standard Deviation 25.9 |
Comparison: Exploratory comparison between SABER-Bupivacaine and Bupivacaine HCl not analyzed inferentiallyp-value: 0.33195% CI: [-7.59, 2.58]t-test in ANOVA model
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
Population: ITT population (patients with data available)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SABER-Bupivacaine | Opioid Related Side Effects | 0.28 score on a scale | Standard Deviation 0.28 |
| SABER-placebo | Opioid Related Side Effects | 0.34 score on a scale | Standard Deviation 0.31 |
| Bupivacaine HCl | Opioid Related Side Effects | 0.27 score on a scale | Standard Deviation 0.24 |
Secondary
Time to First Opioid Rescue Medication Usage
Time frame: 0-14 days after surgery
Population: ITT population (patients with data available)
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| SABER-Bupivacaine | Time to First Opioid Rescue Medication Usage | 7.71 hours | Standard Deviation 45.79 |
| SABER-placebo | Time to First Opioid Rescue Medication Usage | 1.53 hours | Standard Deviation 1.56 |
| Bupivacaine HCl | Time to First Opioid Rescue Medication Usage | 87.77 hours | Standard Deviation 1.11 |