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Tramadol Versus Placebo in the Management of Postoperative Pain Following Bunionectomy

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ClinicalTrials.gov Identifier: NCT03290378
Recruitment Status : Completed
First Posted : September 21, 2017
Results First Posted : March 19, 2020
Last Update Posted : March 19, 2020
Sponsor:
Information provided by (Responsible Party):
Avenue Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Pain Management
Interventions Drug: Tramadol
Other: Placebo
Enrollment 409
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AVE-901 50 mg AVE-901 25 mg Placebo
Hide 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
Arm/Group Title AVE-901 50 mg AVE-901 25 mg Placebo Total
Hide 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 Number of Baseline Participants 139 134 136 409
Hide Baseline Analysis Population Description
Patient 03-042 was randomized to tramadol 25 mg but received tramadol 50 mg in error.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 139 participants 134 participants 136 participants 409 participants
45.3  (13.51) 44.5  (13.15) 45.0  (13.44) 45.2  (13.35)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 134 participants 136 participants 409 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 134 participants 136 participants 409 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
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 134 participants 136 participants 409 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
   0.0%
1
   0.7%
0
   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
   0.0%
1
   0.7%
0
   0.0%
1
   0.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 139 participants 134 participants 136 participants 409 participants
139
 100.0%
134
 100.0%
136
 100.0%
409
 100.0%
Previous opioid history  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 134 participants 136 participants 409 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   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 134 participants 136 participants 409 participants
1
70
  50.4%
71
  53.0%
72
  52.9%
213
  52.1%
2
69
  49.6%
63
  47.0%
64
  47.1%
196
  47.9%
[1]
Measure Description:

Patient was to meet definition of American Society of Anesthesiologists (ASA) Physical Class of I or II:

ASA I) normal healthy patient: healthy, non-smoking, no or minimal alcohol use) or

ASA II) A patient with mild systemic disease: Mild diseases only without substantive functional limitations. Examples include (but not limited to): current smoker, social alcohol drinker, pregnancy, obesity (30<BMI<40), well-controlled DM/HTN, mild lug disease.

Qualifying Categorical Pain Score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 134 participants 136 participants 409 participants
Moderate
89
  64.0%
80
  59.7%
75
  55.1%
244
  59.7%
Severe
50
  36.0%
54
  40.3%
61
  44.9%
165
  40.3%
[1]
Measure Description: The patient reported a score of moderate or severe on a 4-point categorical rating scale (with categories of none, mild, moderate, or severe)
BMI   [1] 
Median (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 139 participants 134 participants 136 participants 409 participants
27.9  (4.97) 28.1  (5.48) 28.3  (4.91) 28.1  (5.12)
[1]
Measure Description: BMI Calculation: Sites used the NIH website BMI calculator: https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm
Qualifying Numerical Pain Rating Scale (NPRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 139 participants 134 participants 136 participants 409 participants
6.7  (1.66) 6.8  (1.39) 6.9  (1.63) 6.8  (1.56)
[1]
Measure Description:

Patient recorded a pain score ≥5, within 8 hours after removal of popliteal block, on an Numerical Pain Rating Scale (NPRS) where 0 is no pain and 10 is the worst pain imaginable. Patient needed to have a pain score of ≥5 to qualify for the study.

Mean pain score per treatment group noted below.

1.Primary Outcome
Title The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 139 134 136
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-122.8
(-135.14 to -110.50)
-110.9
(-123.64 to -98.17)
-97.8
(-110.60 to -85.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AVE-901 50 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Time Frame 6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AVE-901 50 mg AVE-901 25 mg Placebo
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/140 (0.00%)   0/133 (0.00%)   0/136 (0.00%) 
Hide Serious Adverse Events
AVE-901 50 mg AVE-901 25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/140 (0.00%)   1/133 (0.75%)   0/136 (0.00%) 
General disorders       
non-cardiac chest pain   0/140 (0.00%)  1/133 (0.75%)  0/136 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
AVE-901 50 mg AVE-901 25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   93/140 (66.43%)   56/133 (42.11%)   60/136 (44.12%) 
Gastrointestinal disorders       
Nausea   45/140 (32.14%)  12/133 (9.02%)  11/136 (8.09%) 
Vomiting   28/140 (20.00%)  4/133 (3.01%)  5/136 (3.68%) 
Constipation   8/140 (5.71%)  3/133 (2.26%)  3/136 (2.21%) 
Pruritus generalized   4/140 (2.86%)  3/133 (2.26%)  1/136 (0.74%) 
Diarrhea   0/140 (0.00%)  3/133 (2.26%)  2/136 (1.47%) 
Decreased Appetite   0/140 (0.00%)  1/133 (0.75%)  3/136 (2.21%) 
General disorders       
Infusion Site Pain   11/140 (7.86%)  5/133 (3.76%)  10/136 (7.35%) 
Infusion site extravasation   5/140 (3.57%)  7/133 (5.26%)  5/136 (3.68%) 
Rash   0/140 (0.00%)  3/133 (2.26%)  0/136 (0.00%) 
Nervous system disorders       
Headache   8/140 (5.71%)  14/133 (10.53%)  13/136 (9.56%) 
Dizziness   21/140 (15.00%)  7/133 (5.26%)  4/136 (2.94%) 
Somnolence   16/140 (11.43%)  6/133 (4.51%)  3/136 (2.21%) 
Muscle Twitching   0/140 (0.00%)  3/133 (2.26%)  1/136 (0.74%) 
Respiratory, thoracic and mediastinal disorders       
Hypoxia   5/140 (3.57%)  0/133 (0.00%)  1/136 (0.74%) 
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: VP of Clinical Operations and Program Management
Organization: Avenue Therapeutics
Phone: 781-652-4514
EMail: mryan@avenuetx.com
Layout table for additonal information
Responsible Party: Avenue Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03290378    
Other Study ID Numbers: AVE-901-102
First Submitted: September 19, 2017
First Posted: September 21, 2017
Results First Submitted: May 10, 2019
Results First Posted: March 19, 2020
Last Update Posted: March 19, 2020