Trial Outcomes & Findings for An International Trial to Evaluate the Efficacy and Safety of SABER®-Bupivacaine for Postoperative Pain Control in Patients Undergoing Hysterectomy (NCT NCT00993226)

NCT ID: NCT00993226

Last Updated: 2021-06-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

115 participants

Primary outcome timeframe

1 to 72 hours post-surgery

Results posted on

2021-06-01

Participant Flow

Participant milestones

Participant milestones
Measure
SABER-Bupivacaine
5 mL, single dose instilled into surgical incision
SABER-placebo
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
0.25% 40 mL, single dose infiltrated peri-incisionally
Overall Study
STARTED
61
27
27
Overall Study
COMPLETED
60
26
27
Overall Study
NOT COMPLETED
1
1
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 Undergoing Hysterectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SABER-Bupivacaine
n=61 Participants
5 mL, single dose instilled into surgical incision
SABER-placebo
n=27 Participants
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
n=27 Participants
0.25% 40 mL, single dose infiltrated peri-incisionally
Total
n=115 Participants
Total of all reporting groups
Age, Continuous
46.7 years
n=5 Participants
44.3 years
n=7 Participants
45.1 years
n=5 Participants
45.8 years
n=4 Participants
Sex: Female, Male
Female
61 Participants
n=5 Participants
27 Participants
n=7 Participants
27 Participants
n=5 Participants
115 Participants
n=4 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
BMI
26.1 kg/m^2
n=5 Participants
26.2 kg/m^2
n=7 Participants
27.0 kg/m^2
n=5 Participants
26.4 kg/m^2
n=4 Participants

PRIMARY outcome

Timeframe: 1 to 72 hours post-surgery

Population: ITT population (patients with data available)

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.

Outcome measures

Outcome measures
Measure
SABER-Bupivacaine
n=60 Participants
5 mL, single dose instilled into surgical incision
SABER-placebo
n=27 Participants
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
n=27 Participants
0.25% 40 mL, single dose infiltrated peri-incisionally
Pain Intensity (PI)
4.15 score on a scale
Standard Deviation 1.74
4.46 score on a scale
Standard Deviation 1.48
4.27 score on a scale
Standard Deviation 1.69

PRIMARY outcome

Timeframe: 0-3 days after surgery

Population: ITT population (patients with data available)

Cumulative IV morphine-equivalent dose of opioid rescue medication

Outcome measures

Outcome measures
Measure
SABER-Bupivacaine
n=61 Participants
5 mL, single dose instilled into surgical incision
SABER-placebo
n=27 Participants
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
n=27 Participants
0.25% 40 mL, single dose infiltrated peri-incisionally
Supplemental Opioid Use
22.8 mg
Standard Deviation 24.3
26.3 mg
Standard Deviation 25.7
23.9 mg
Standard Deviation 25.9

SECONDARY outcome

Timeframe: 0-14 days after surgery

Population: ITT population (patients with data available)

Outcome measures

Outcome measures
Measure
SABER-Bupivacaine
n=61 Participants
5 mL, single dose instilled into surgical incision
SABER-placebo
n=27 Participants
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
n=27 Participants
0.25% 40 mL, single dose infiltrated peri-incisionally
Time to First Opioid Rescue Medication Usage
7.71 hours
Standard Deviation 45.79
1.53 hours
Standard Deviation 1.56
87.77 hours
Standard Deviation 1.11

SECONDARY outcome

Timeframe: 0-7 days after surgery

Population: ITT population (patients with data available)

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=53 Participants
5 mL, single dose instilled into surgical incision
SABER-placebo
n=25 Participants
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
n=23 Participants
0.25% 40 mL, single dose infiltrated peri-incisionally
Opioid Related Side Effects
0.28 score on a scale
Standard Deviation 0.28
0.34 score on a scale
Standard Deviation 0.31
0.27 score on a scale
Standard Deviation 0.24

Adverse Events

SABER-Bupivacaine

Serious events: 7 serious events
Other events: 48 other events
Deaths: 0 deaths

SABER-placebo

Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths

Bupivacaine HCl

Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
SABER-Bupivacaine
n=60 participants at risk
5 mL, single dose instilled into surgical incision
SABER-placebo
n=27 participants at risk
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
n=27 participants at risk
0.25% 40 mL, single dose infiltrated peri-incisionally
Investigations
ECG abnormal
3.3%
2/60
0.00%
0/27
0.00%
0/27
Investigations
ECG QT prolonged
1.7%
1/60
0.00%
0/27
0.00%
0/27
Infections and infestations
Haematoma infection
3.3%
2/60
0.00%
0/27
0.00%
0/27
Respiratory, thoracic and mediastinal disorders
Bronchospasm
1.7%
1/60
0.00%
0/27
0.00%
0/27
Respiratory, thoracic and mediastinal disorders
Laryngeal oedema
1.7%
1/60
0.00%
0/27
0.00%
0/27
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
1.7%
1/60
0.00%
0/27
0.00%
0/27

Other adverse events

Other adverse events
Measure
SABER-Bupivacaine
n=60 participants at risk
5 mL, single dose instilled into surgical incision
SABER-placebo
n=27 participants at risk
5 mL, single dose instilled into surgical incision
Bupivacaine HCl
n=27 participants at risk
0.25% 40 mL, single dose infiltrated peri-incisionally
Injury, poisoning and procedural complications
Post procedural contusion
60.0%
36/60
33.3%
9/27
0.00%
0/27
Blood and lymphatic system disorders
Anaemia
16.7%
10/60
14.8%
4/27
11.1%
3/27
Gastrointestinal disorders
Vomiting
15.0%
9/60
29.6%
8/27
14.8%
4/27
Nervous system disorders
Dizziness
15.0%
9/60
11.1%
3/27
14.8%
4/27
General disorders
Pyrexia
11.7%
7/60
11.1%
3/27
25.9%
7/27
Investigations
CRP increased
11.7%
7/60
0.00%
0/27
3.7%
1/27
Nervous system disorders
Somnolence
8.3%
5/60
0.00%
0/27
7.4%
2/27
Investigations
Blood potassium decreased
6.7%
4/60
3.7%
1/27
0.00%
0/27
Vascular disorders
Hypertension
6.7%
4/60
3.7%
1/27
7.4%
2/27
Injury, poisoning and procedural complications
Incision site haematoma
5.0%
3/60
0.00%
0/27
0.00%
0/27

Additional Information

Deborah Scott

Durect Corporation

Phone: 408-777-1417

Results disclosure agreements

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