A Randomized, Multicenter, Pilot Study Comparing the Efficacy and Safety of a Bupivacaine-Collagen Implant (XaraColl®) with the ON-Q PainBuster® Post-op Pain Relief System Following Open Gynecological Surgery
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Design
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Randomized, multicenter, pilot study
N= 27
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Objective
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To compare the efficacy and safety of XaraColl for the prevention of postsurgical pain versus a slow postoperative perfusion of bupivacaine to the wound environment via the ON-Q PainBuster® Post-op Pain Relief System (ON-Q)
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Study Groups
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XaraColl® (n=14)
ON-Q (n=13)
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Inclusion Criteria
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Women at least 18 years of age, generally healthy, scheduled to receive an elective total abdominal hysterectomy or other nonlaparoscopic gynecological procedure for reasons other than malignancy (e.g., adenocarcinoma, cervical cancer, or leiomyosarcoma) under general anesthesia.
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Exclusion Criteria
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Laparoscopic procedures, supraumbilical or Maylard incisions, or concomitant vaginal procedures (e.g., anterior and posterior colporrhaphy), any additional surgical procedures either related or unrelated to abdominal hysterectomy during the same hospitalization, neuraxial opioid analgesics during the surgery, use of an adhesion barrier, chronic painful conditions or other concomitant illness with agents that could affect the analgesic response (e.g., central alpha agents, neuroleptic agents, and other antipsychotic agents, monoamine oxidase inhibitors, or systemic corticosteroids), unreliable or incapable of complying with the requirements of the protocol.
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Methods
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Eligible patients undergoing open gynecological surgery were randomized (1:1) to receive either three XaraColl implants (each containing 50 mg bupivacaine hydrochloride) or ON-Q (900 mg bupivacaine hydrochloride perfused over 72 hours). Following surgery, patients had access to intravenous (IV) morphine via a patient-controlled analgesia (PCA) pump as rescue analgesia for the first 24 hours and to oral opioid medication thereafter.
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Duration
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September 2008 to December 2008
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Outcome Measures
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Primary: Total use of opioid analgesia through 24, 48, 72, and 96 hours after surgery.
Secondary: Time to first use of opioid rescue analgesia, patients' overall pain control over the 96-hour period using a five-point numeric rating scale, adverse events.
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Baseline Characteristics
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XaraColl®
(n=14)
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ON-Q
(n=13)
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Age, years
Mean (standard deviation [SD])
Median (minimum, maximum)
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43.3 (11.5)
39.0 (28, 63)
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43.4 (6.2)
41.0 (36, 59)
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Race
Asian
Black or African American
White or Caucasian
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1 (7.1%)
2 (14.3%)
11 (78.6%)
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0 (0.0%)
5 (38.5%)
8 (61.5%)
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Ethnicity
Hispanic or Latino
Not Hispanic or Latino
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3 (21.4%)
11 (78.6%)
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0 (0.0%)
13 (100.0%)
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Weight, kg
Mean (SD)
Median (minimum, maximum)
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71.7 (12.8)
77.0 (53.6, 90.5)
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73.3 (11.0)
74.1 (56.4, 93.6)
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Height, cm
Mean (SD)
Median (minimum, maximum)
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162.1 (6.4)
161.3 (150.0, 171.0)
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160.2 (8.6)
162.6 (139.7, 175.0)
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Body mass index, kg/m2
Mean (SD)
Median (minimum, maximum)
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27.1 (3.8)
27.6 (21.4, 32.5)
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28.7 (4.6)
29.0 (22.9, 37.0)
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Surgical procedure performed
Abdominal hysterectomy
Myomectomy
Abdominal hysterectomy with right salpingo-oophorectomy
Right salpingo-oophorectomy (adnexal only)
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10 (71.4%)
3 (21.4%)
1 (7.1%)
0 (0.0%)
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11 (84.6%)
1 (7.7%)
0 (0.0%)
1 (7.7%)
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Results
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Treatment group
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Non-inferiority and superiority statistics
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Total opioid use from 0 to 24 hours |
XaraColl® |
ON-Q |
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Mean (SD) |
46.9 (21.6) |
67.0 (32.4) |
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Mean difference |
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−20.2 |
Upper bound of one-sided 95% CI of the mean difference |
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−2.20 |
P-value* |
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p=0.067 |
Total opioid use from 0 to 48 hours |
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Mean (SD) |
55.4 (22.8) |
74.9 (35.4) |
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Mean difference |
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−19.4 |
Upper bound of one-sided 95% CI of the mean difference |
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−0.01 |
P-value* |
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p=0.100 |
Total opioid use from 0 to 72 hours |
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Mean (SD) |
62.0 (25.3) |
85.4 (41.9) |
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Mean difference |
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−23.4 |
Upper bound of one-sided 95% CI of the mean difference |
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−0.84 |
P-value* |
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p=0.089 |
Total opioid use from 0 to 96 hours |
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Mean (SD) |
67.9 (28.2) |
90.8 (46.1) |
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Mean difference |
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−22.9 |
Upper bound of one-sided 95% CI of the mean difference |
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2.01 |
P-value* |
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p=0.129 |
The time to first use of opioid analgesia was significantly delayed in patients treated with XaraColl (p=0.024). Fifty percent of patients took their first opioid medication at 0.78 and 0.57 hours after time 0 in the XaraColl and ON-Q groups, respectively.
Overall, there was no significant difference in the patients’ rating of pain control (p=0.847).
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Adverse Events
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Common Adverse Events: Constipation (14.3% XaraColl® vs. 0.0% ON-Q), flatulence (14.3% vs. 0.0%), nausea (7.1% vs. 15.4%), pyrexia (7.1% vs. 15.4%), headache (14.3% vs. 7.7%), rash (14.3% vs. 0.0%)
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Serious Adverse Events: 0%
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Percentage that Discontinued due to Adverse Events: 0%
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Study Author Conclusions
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Despite using only 17% of the ON-Q dose, XaraColl is as effective as ON-Q in providing postoperative analgesia for 4 days after open gynecological surgery. These preliminary findings suggest that XaraColl offers great potential for the management of postoperative pain and warrants further definitive studies.
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InpharmD Researcher Critique
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This could be considered an underpowered hypothesis-generating pilot study. Participants and investigators were non-blinded due to fundamentally different treatment modalities. The principal efficacy endpoint was patient use of opioid analgesia which can be readily influenced by confounding factors such as patient attitudes and educations.
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