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Efficacy of Extended Release Tramadol for Treating Prescription Opioid Withdrawal

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ClinicalTrials.gov Identifier: NCT00980044
Recruitment Status : Completed
First Posted : September 18, 2009
Results First Posted : December 3, 2014
Last Update Posted : April 5, 2017
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Michelle Lofwall, University of Kentucky

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Substance Withdrawal Syndrome
Interventions Drug: Tramadol
Drug: Placebo
Enrollment 53
Recruitment Details Outpatient screening. Recruitment by advertisement and word or mouth.
Pre-assignment Details

Persons screening who did not meet inclusion/ exclusion criteria were not enrolled.

Persons who did not complete the study were not included in analyses. The study was designed as an efficacy study that a priori stated it would enroll until 12 persons in each group completed the study and analyse only completers. No serious AEs in noncompleters.

Arm/Group Title Tramadol 200 mg Daily Placebo Tramadol 600 mg Daily
Hide Arm/Group Description Medication: Extended release tramadol 200 mg daily given for 1 week then placebo given for 1 week Placebo given for two weeks Medication: Extended release tramadol 600 mg daily given for 1 week followed by 1 week of placebo dosing.
Period Title: Overall Study
Started 17 19 17
Completed 12 12 12
Not Completed 5 7 5
Reason Not Completed
Withdrawal by Subject             5             7             3
Protocol Violation             0             0             2
Arm/Group Title Tramadol 200 mg Placebo Tramadol 600 mg Total
Hide Arm/Group Description Medication: Extended release tramadol for 1 week and then placebo given for 1 week Medication: Placebo given for two weeks Medication: Extended release tramadol 600 mg given for 1 week and then placebo given for 1 week Total of all reporting groups
Overall Number of Baseline Participants 12 12 12 36
Hide Baseline Analysis Population Description
The study was a priori defined to evaluate only completers. There were 12 completers in each of the three study arms. We retained the description of the completers because it corresponds to the primary outcomes results that are reported (and this is what was proposed a priori and approved by NIDA review).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
12
 100.0%
12
 100.0%
12
 100.0%
36
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 12 participants 36 participants
26.8  (0.9) 32.2  (2.2) 31.6  (1.5) 30.1  (1.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Female
5
  41.7%
4
  33.3%
5
  41.7%
14
  38.9%
Male
7
  58.3%
8
  66.7%
7
  58.3%
22
  61.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 12 participants 12 participants 12 participants 36 participants
12 12 12 36
1.Primary Outcome
Title Subjective Opioid Withdrawal Total Adjective Score
Hide Description range of scores is 0-84; low scores indicate no opioid withdrawal, higher scores indicating more opioid withdrawal present. T
Time Frame Days 1-7
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean across the days listed.
Arm/Group Title Tramadol 200 mg Daily Placebo Tramadol 600 mg Daily
Hide Arm/Group Description:
Medication: Extended release tramadol
Medication
Medication: Extended release tramadol
Overall Number of Participants Analyzed 12 12 12
Mean (Standard Error)
Unit of Measure: units on a scale
5.8  (0.1) 7.7  (0.1) 6.9  (0.1)
2.Primary Outcome
Title Total Number of Breakthrough Withdrawal Medication Doses Taken Week 1
Hide Description There were four medications (acetaminophen for aches/pains, zolpidem for trouble sleeping, bismuth subsalicylate for diarrhea, and alumina/magnesia/simethicone for nausea/upset stomach) available to all volunteers in all treatment arms to help relieve any withdrawal symptoms that were not relieved by the blinded tramadol/placebo doses.
Time Frame Days 1-7
Hide Outcome Measure Data
Hide Analysis Population Description
These are data from week 1 -- the 12 people who completed this week in each group. This is the analysis that was specified at the start of the study. The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean across the days listed.
Arm/Group Title Tramadol 200 mg Then Placebo Placebo for Two Weeks Tramadol 600 mg Then Placebo
Hide Arm/Group Description:

Tramadol 200 mg daily for 1 week then placebo given for 1 week

Tramadol: Oral Medication

Medication

Placebo: Oral Medication

Tramadol 600 mg daily given for 1 week given then placebo given for 1 week

Tramadol: Oral Medication

Overall Number of Participants Analyzed 12 12 12
Mean (Standard Error)
Unit of Measure: Mean doses per day
1.8  (0.2) 2.5  (0.2) 3.1  (0.3)
3.Primary Outcome
Title Subjective Opioid Withdrawal Adjective Total Score Week 2
Hide Description range of scores is 0-84; low scores indicate no opioid withdrawal, higher scores indicating more opioid withdrawal present
Time Frame days 8-13
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean total withdrawal score across the days listed.
Arm/Group Title Tramadol 200 mg Then Placebo Placebo for Two Weeks Tramadol 600 mg Then Placebo
Hide Arm/Group Description:

Tramadol 200 mg daily for 1 week then placebo given for 1 week

Tramadol: Oral Medication

Medication

Placebo: Oral Medication

Tramadol 600 mg daily given for 1 week given then placebo given for 1 week

Tramadol: Oral Medication

Overall Number of Participants Analyzed 12 12 12
Mean (Standard Error)
Unit of Measure: units on a scale
2.7  (0.2) 2.9  (0.2) 2.7  (0.1)
4.Primary Outcome
Title Total Number of Breakthrough Withdrawal Medication Doses Taken Week 2
Hide Description There were four medications (acetaminophen for aches/pains, zolpidem for trouble sleeping, bismuth subsalicylate for diarrhea, and alumina/magnesia/simethicone for nausea/upset stomach) available to all volunteers in all treatment arms to help relieve any withdrawal symptoms that were not relieved by the blinded tramadol/placebo doses.
Time Frame Days 8-13 (all groups now on placebo)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean number of doses/day across the days listed.
Arm/Group Title Tramadol 200 mg Then Placebo Placebo for Two Weeks Tramadol 600 mg Then Placebo
Hide Arm/Group Description:

Tramadol 200 mg daily for 1 week then placebo given for 1 week

Tramadol: Oral Medication

Medication

Placebo: Oral Medication

Tramadol 600 mg daily given for 1 week given then placebo given for 1 week

Tramadol: Oral Medication

Overall Number of Participants Analyzed 12 12 12
Mean (Standard Error)
Unit of Measure: mean # of doses per day
1.8  (0.2) 1.6  (0.1) 3.2  (0.2)
Time Frame [Not Specified]
Adverse Event Reporting Description There were no serious adverse events for anyone enrolled (completers and non-completers). The remaining adverse events are reported from both completers and non-completers.
 
Arm/Group Title Tramadol 200 mg Placebo Tramadol 600 mg
Hide Arm/Group Description Medication: Extended release tramadol 200 mg daily for one week followed by placebo for one week Medication: Placebo for 2 weeks Medication: Extended release tramadol 600 mg daily for one week followed by placebo for one week
All-Cause Mortality
Tramadol 200 mg Placebo Tramadol 600 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Tramadol 200 mg Placebo Tramadol 600 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/17 (0.00%)      0/19 (0.00%)      0/17 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tramadol 200 mg Placebo Tramadol 600 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/17 (11.76%)      1/19 (5.26%)      2/17 (11.76%)    
Gastrointestinal disorders       
abdominal pain  [1]  1/17 (5.88%)  1 1/19 (5.26%)  1 0/17 (0.00%)  0
Infections and infestations       
sore throat/strep B  [1]  0/17 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1
sore throat with cough  [2]  0/17 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1
athletes foot  [2]  1/17 (5.88%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0
Musculoskeletal and connective tissue disorders       
fleeting chest pain  [1]  1/17 (5.88%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0
left shoulder pain  [3]  0/17 (0.00%)  0 1/19 (5.26%)  1 0/17 (0.00%)  0
tooth pain  [4]  0/17 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1
flank pain  [5]  0/17 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1
Renal and urinary disorders       
unsteady urine flow without dysuria  [1]  0/17 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1
Indicates events were collected by systematic assessment
[1]
Occurred in a completer
[2]
Occurred in a non-completer.
[3]
Pre-existing condition -- pain due to old MVA whereby shoulder was hurt. Occurred in a non-completer.
[4]
Cracked right front tooth prior to admission to study - now with mild pain in that tooth. Occurred in a non-completer.
[5]
right sided flank pain that started 2 days prior to randomization, mild severity, occurs when twisting body. Occurred in a non-completer.
The study was designed to analyze only completers (12 subjects per group so the description of study participant characteristics and outcomes are from these a prior defined n=36 (12 per group) completers.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Michelle Lofwall, MD, Associate Professor
Organization: University of Kentucky College of Medicine
Phone: 8593239321
Responsible Party: Michelle Lofwall, University of Kentucky
ClinicalTrials.gov Identifier: NCT00980044     History of Changes
Other Study ID Numbers: 09-0489
R01DA027068 ( U.S. NIH Grant/Contract )
First Submitted: September 17, 2009
First Posted: September 18, 2009
Results First Submitted: June 10, 2013
Results First Posted: December 3, 2014
Last Update Posted: April 5, 2017