Tramadol Versus Placebo in the Management of Postoperative Pain Following Bunionectomy
Study Details
Study Description
Brief Summary
The study evaluates the effectiveness and safety of IV tramadol compared to placebo managing postoperative pain following a bunionectomy
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
(Non-clinical summary)
Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with opioidlike effects. Tramadol is extensively metabolized following administration, which results in a number of enantiomeric metabolites that display different opioid-receptor binding properties, and monoaminergic reuptake inhibition.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: AVE-901 50 mg
|
Drug: Tramadol
IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
|
| Active Comparator: AVE-901 25 mg
|
Drug: Tramadol
IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
|
| Placebo Comparator: Placebo
|
Other: Placebo
IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
|
Outcome Measures
Primary Outcome Measures
- The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose [48 hours post first dose]
Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
The patient is male or female 18-75 years of age undergoing unilateral first metatarsal bunionectomy surgery
-
Willing to give consent and able to understand the study procedures
-
Female patients must be of non-childbearing potential or be practicing a highly effective contraception
-
The patient must be willing to be housed in a healthcare facility and able to receive parenteral analgesia for at least 72 hours after surgery.
-
The patient meets definition of American Society of Anesthesiologists (ASA) Physical Class 1, or 2.
Exclusion Criteria:
-
Patient is not expected to receive a continuous infusion nerve block as described in the Post-Op anesthetic procedures protocol
-
Patient is undergoing bilateral or revision bunionectomy surgery
-
The patient has allergy or hypersensitivity (or is intolerant) to opioids or tramadol The patient has known physical dependence on opioids
-
The patient has taken other prior/concurrent chronic medications that have not been at a stable dose for at least 2 weeks prior to screening
-
The patient is taking herbal or dietary supplements or medications that are moderate or strong inhibitors of CYP2D6 or CYP3A4 or inducers of CYP3A4
-
The patient has taken monoamine oxidase (MAO) inhibitors, trazodone, or cyclobenzaprine within 14 days prior to surgery
-
The patient cannot be withdrawn from medications (at least 7 days prior to surgery) that may lower the seizure threshold (e.g. anti-psychotic agents, MAOI inhibitors) or which increase serotonergic tone (e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, triptans).
-
The patient has a history of epilepsy, or is known to be susceptible to seizures
-
The patient has a history of Long QT Syndrome or a relative with this condition
-
The patient has expressed suicidal ideation or is considered to be at risk of suicide.
-
The patient is morbidly obese (body mass index [BMI] ≥ 40 kg/m2) or has documented sleep apnea requiring pharmacological or device intervention.
-
Clinically significant abnormalities in the judgement of the Investigator
-
The patient was administered an investigational product within 30 days prior to Screening.
-
The patient has previously participated in a clinical study with AVE-901.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Trovare Clinical Research | Bakersfield | California | United States | 93301 |
| 2 | Lotus Clinical Research | Pasadena | California | United States | 91105 |
| 3 | Cheseapeake Research Group, LLC | Pasadena | Maryland | United States | 21122 |
| 4 | H.D. Research Corporation | Houston | Texas | United States | 77004 |
| 5 | Endeavor Clinical Trials, PA | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Avenue Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- AVE-901-102
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | AVE-901 50 mg | AVE-901 25 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 |
| Period Title: Overall Study | |||
| STARTED | 140 | 133 | 136 |
| COMPLETED | 137 | 123 | 120 |
| NOT COMPLETED | 3 | 10 | 16 |
Baseline Characteristics
| Arm/Group Title | AVE-901 50 mg | AVE-901 25 mg | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Total of all reporting groups |
| Overall Participants | 139 | 134 | 136 | 409 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
45.3
(13.51)
|
44.5
(13.15)
|
45.0
(13.44)
|
45.2
(13.35)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
120
86.3%
|
116
86.6%
|
113
83.1%
|
349
85.3%
|
| Male |
19
13.7%
|
18
13.4%
|
23
16.9%
|
60
14.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
51
36.7%
|
46
34.3%
|
52
38.2%
|
149
36.4%
|
| Not Hispanic or Latino |
88
63.3%
|
88
65.7%
|
84
61.8%
|
260
63.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
2
1.4%
|
1
0.7%
|
4
2.9%
|
7
1.7%
|
| Asian |
2
1.4%
|
3
2.2%
|
4
2.9%
|
9
2.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.7%
|
0
0%
|
1
0.2%
|
| Black or African American |
29
20.9%
|
38
28.4%
|
37
27.2%
|
104
25.4%
|
| White |
104
74.8%
|
88
65.7%
|
88
64.7%
|
280
68.5%
|
| More than one race |
2
1.4%
|
2
1.5%
|
3
2.2%
|
7
1.7%
|
| Unknown or Not Reported |
0
0%
|
1
0.7%
|
0
0%
|
1
0.2%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
139
100%
|
134
100%
|
136
100%
|
409
100%
|
| Previous opioid history (Count of Participants) | ||||
| Yes |
42
30.2%
|
52
38.8%
|
47
34.6%
|
141
34.5%
|
| No |
97
69.8%
|
82
61.2%
|
89
65.4%
|
268
65.5%
|
| American Society of Anesthesiology (ASA) Physical Classification (Count of Participants) | ||||
| 1 |
70
50.4%
|
71
53%
|
72
52.9%
|
213
52.1%
|
| 2 |
69
49.6%
|
63
47%
|
64
47.1%
|
196
47.9%
|
| Qualifying Categorical Pain Score (Count of Participants) | ||||
| Moderate |
89
64%
|
80
59.7%
|
75
55.1%
|
244
59.7%
|
| Severe |
50
36%
|
54
40.3%
|
61
44.9%
|
165
40.3%
|
| BMI (kg/m2) [Median (Standard Deviation) ] | ||||
| Median (Standard Deviation) [kg/m2] |
27.9
(4.97)
|
28.1
(5.48)
|
28.3
(4.91)
|
28.1
(5.12)
|
| Qualifying Numerical Pain Rating Scale (NPRS) (score on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [score on a scale] |
6.7
(1.66)
|
6.8
(1.39)
|
6.9
(1.63)
|
6.8
(1.56)
|
Outcome Measures
| Title | The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose |
|---|---|
| Description | Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity. |
| Time Frame | 48 hours post first dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| One patient was randomized to tramadol 25 mg but received tramadol 50 mg in error. |
| Arm/Group Title | AVE-901 50 mg | AVE-901 25 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 |
| Measure Participants | 139 | 134 | 136 |
| Least Squares Mean (95% Confidence Interval) [score on a scale] |
-122.8
|
-110.9
|
-97.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | AVE-901 50 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Adverse Events
| Time Frame | 6 months | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | AVE-901 50 mg | AVE-901 25 mg | Placebo | |||
| Arm/Group Description | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 | |||
All Cause Mortality |
||||||
| AVE-901 50 mg | AVE-901 25 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/140 (0%) | 0/133 (0%) | 0/136 (0%) | |||
Serious Adverse Events |
||||||
| AVE-901 50 mg | AVE-901 25 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/140 (0%) | 1/133 (0.8%) | 0/136 (0%) | |||
| General disorders | ||||||
| non-cardiac chest pain | 0/140 (0%) | 1/133 (0.8%) | 0/136 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| AVE-901 50 mg | AVE-901 25 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 93/140 (66.4%) | 56/133 (42.1%) | 60/136 (44.1%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 45/140 (32.1%) | 12/133 (9%) | 11/136 (8.1%) | |||
| Vomiting | 28/140 (20%) | 4/133 (3%) | 5/136 (3.7%) | |||
| Constipation | 8/140 (5.7%) | 3/133 (2.3%) | 3/136 (2.2%) | |||
| Pruritus generalized | 4/140 (2.9%) | 3/133 (2.3%) | 1/136 (0.7%) | |||
| Diarrhea | 0/140 (0%) | 3/133 (2.3%) | 2/136 (1.5%) | |||
| Decreased Appetite | 0/140 (0%) | 1/133 (0.8%) | 3/136 (2.2%) | |||
| General disorders | ||||||
| Infusion Site Pain | 11/140 (7.9%) | 5/133 (3.8%) | 10/136 (7.4%) | |||
| Infusion site extravasation | 5/140 (3.6%) | 7/133 (5.3%) | 5/136 (3.7%) | |||
| Rash | 0/140 (0%) | 3/133 (2.3%) | 0/136 (0%) | |||
| Nervous system disorders | ||||||
| Headache | 8/140 (5.7%) | 14/133 (10.5%) | 13/136 (9.6%) | |||
| Dizziness | 21/140 (15%) | 7/133 (5.3%) | 4/136 (2.9%) | |||
| Somnolence | 16/140 (11.4%) | 6/133 (4.5%) | 3/136 (2.2%) | |||
| Muscle Twitching | 0/140 (0%) | 3/133 (2.3%) | 1/136 (0.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Hypoxia | 5/140 (3.6%) | 0/133 (0%) | 1/136 (0.7%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | VP of Clinical Operations and Program Management |
|---|---|
| Organization | Avenue Therapeutics |
| Phone | 781-652-4514 |
| mryan@avenuetx.com |
- AVE-901-102