A Four-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol Once a Day 100, 200 and 300 mg Versus Placebo for the Treatment of Pain Due to Osteoarthritis of the Knee (With 7-Day Follow-up)
Primary Purpose
Pain
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tramadol Once A Day
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pain focused on measuring Pain due to Osteoarthritis of the Knee
Eligibility Criteria
Inclusion Criteria:
Males or Females between the ages of 40-75 with a diagnosis of moderate to severe osteoarthritis of the knee, consistent with the ACR Clinical Classification Criteria for Arthritis of the Knee:
- Current knee pain.
- Less than 30 minutes of morning stiffness with or without crepitus on active motion.
- Confirmation either by arthroscopy or radiologist's report (X-rays showing osteophytes, joint space narrowing or subchondral bone sclerosis {eburnation}) within five years prior to entry into the study.
- CRP < 8 ug/mL (if available at local lab) or ESR < 40 mm/hr.
- Total WOMAC (Western Ontario and McMaster University Osteoarthritis Index) Pain Subscale Score of > 150 mm at Baseline corresponding with moderate to severe Osteoarthritis.
- Oral and written language comprehension at a level sufficient to comply with the protocol and complete study-related materials.
- REB approval of the written Informed Consent Form in Spanish or English which was signed and dated by the patient and Investigator, prior to study participation.
Exclusion Criteria:
- Known rheumatoid arthritis or any other rheumatoid disease.
- Secondary arthritis i.e. any of the following: septic arthritis; inflammatory joint disease; gout; pseudogout; Paget's disease; joint fracture; acromegaly; fibromyalgia; Wilson's disease; ochronosis; haemochromatosis; osteochondromatosis; or collagen gene mutations.
- Evidence of effusion greater than 15 cc upon physical examination of the joint at Baseline (Visit 1).
- BMI greater than or equal to 38.
- Major illness, requiring hospitalization during the 3 months before commencement of the screening period.
- Unwillingness to stop taking pain medication (for arthritis or other types of pain) or was unwilling to stop taking other medications for the treatment of OA.
- Previous failure or discontinuation (due to adverse events) of tramadol HCl therapy.
- Treatment within the last 3 weeks with any of the following medications: monoamine oxidase inhibitors; tricyclic antidepressants and other tricyclic compounds (e.g. cyclobenzaprine, promethazine); neuroleptics; selective serotonin reuptake inhibitors; or any other drug that reduces seizure threshold.
- Treatment with another investigational agent within the last 30 days.
- A history of seizure disorder other than Infantile Febrile Seizures.
- Previous or current opioid dependency.
- Bowel disease causing malabsorption.
- Pregnancy or lactating or childbearing potential and unwilling to utilize a medically approved method of contraception during participation in this clinical trial.
- Significant liver disease, defined as active hepatitis or elevated liver enzymes >3 times the upper boundary of the normal range.
- Significant renal disease, defined as creatinine clearance <30 mL/min as estimated by the method of Levey et al., 1999.
- Current substance abuse or dependence, other than nicotine.
- Allergy or adverse reaction to tramadol or any structurally similar drugs e.g. opiates.
- Any other condition that, in the opinion of the Investigators, would have adversely affected the patient's ability to complete the study or its measures.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
1: Tramadol Once A Day 100mg
2: Tramadol Once A Day 200mg
3: Tramadol Once A Day 300mg
4: Placebo
Arm Description
Outcomes
Primary Outcome Measures
Patient Global Rating of Pain for the Study Period (12 Weeks)
3-item Likert-scale: "How do you rate overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective". The average of ratings at visits 2-5 was calculated as median, rounded up to the closest integer.
Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)
Percentage of difference in WOMAC Pain Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale (VAS) ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 of the questions.
Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)
Percentage of difference in WOMAC Physical Function Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no difficulty (0mm) to extreme difficulty (100mm). The WOMAC Physical Function subscale results from the sum of 17 of the questions.
Secondary Outcome Measures
Percentage Change in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Percentage of difference in WOMAC Pain Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.
Percentage Change in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Percentage of difference in WOMAC Physical Function Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales. The WOMAC Physical Function Subscale comprises 17 questions each rated on a 100mm visual analog scale (VAS) ranging from no difficulty (0mm) to extreme difficulty (100mm).
Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
Patients rated their knee pain by marking a 100mm Visual Analogue Scale, ranging from no pain (0mm) to extreme pain (100mm).
Investigator Global Rating of Pain Relief
The Investigator Global Rating of Pain is a 3-item Likert-scale to answer the following question: "How do you rate this patient's overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective".
Dropout Rate
Reasons for withdrawal from the trial were collected
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00852917
Brief Title
A Four-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol Once a Day 100, 200 and 300 mg Versus Placebo for the Treatment of Pain Due to Osteoarthritis of the Knee (With 7-Day Follow-up)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
January 2003 (undefined)
Primary Completion Date
August 2003 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Labopharm Inc.
4. Oversight
5. Study Description
Brief Summary
The objective of this study is to compare the analgesic efficacy and safety of Tramadol Once a Day 100, 200, 300 mg and Placebo
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain
Keywords
Pain due to Osteoarthritis of the Knee
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
552 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1: Tramadol Once A Day 100mg
Arm Type
Experimental
Arm Title
2: Tramadol Once A Day 200mg
Arm Type
Experimental
Arm Title
3: Tramadol Once A Day 300mg
Arm Type
Experimental
Arm Title
4: Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Tramadol Once A Day
Intervention Description
One Tramadol Once A Day tablet at randomized dose daily.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One Placebo tablet daily.
Primary Outcome Measure Information:
Title
Patient Global Rating of Pain for the Study Period (12 Weeks)
Description
3-item Likert-scale: "How do you rate overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective". The average of ratings at visits 2-5 was calculated as median, rounded up to the closest integer.
Time Frame
12 weeks
Title
Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)
Description
Percentage of difference in WOMAC Pain Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale (VAS) ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 of the questions.
Time Frame
12 weeks
Title
Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)
Description
Percentage of difference in WOMAC Physical Function Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no difficulty (0mm) to extreme difficulty (100mm). The WOMAC Physical Function subscale results from the sum of 17 of the questions.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Percentage Change in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Description
Percentage of difference in WOMAC Pain Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.
Time Frame
Week 0, week 3, week 6
Title
Percentage Change in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Description
Percentage of difference in WOMAC Physical Function Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales. The WOMAC Physical Function Subscale comprises 17 questions each rated on a 100mm visual analog scale (VAS) ranging from no difficulty (0mm) to extreme difficulty (100mm).
Time Frame
Week 0, week 3, week 6
Title
Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
Description
Patients rated their knee pain by marking a 100mm Visual Analogue Scale, ranging from no pain (0mm) to extreme pain (100mm).
Time Frame
12 weeks
Title
Investigator Global Rating of Pain Relief
Description
The Investigator Global Rating of Pain is a 3-item Likert-scale to answer the following question: "How do you rate this patient's overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective".
Time Frame
12 weeks
Title
Dropout Rate
Description
Reasons for withdrawal from the trial were collected
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or Females between the ages of 40-75 with a diagnosis of moderate to severe osteoarthritis of the knee, consistent with the ACR Clinical Classification Criteria for Arthritis of the Knee:
Current knee pain.
Less than 30 minutes of morning stiffness with or without crepitus on active motion.
Confirmation either by arthroscopy or radiologist's report (X-rays showing osteophytes, joint space narrowing or subchondral bone sclerosis {eburnation}) within five years prior to entry into the study.
CRP < 8 ug/mL (if available at local lab) or ESR < 40 mm/hr.
Total WOMAC (Western Ontario and McMaster University Osteoarthritis Index) Pain Subscale Score of > 150 mm at Baseline corresponding with moderate to severe Osteoarthritis.
Oral and written language comprehension at a level sufficient to comply with the protocol and complete study-related materials.
REB approval of the written Informed Consent Form in Spanish or English which was signed and dated by the patient and Investigator, prior to study participation.
Exclusion Criteria:
Known rheumatoid arthritis or any other rheumatoid disease.
Secondary arthritis i.e. any of the following: septic arthritis; inflammatory joint disease; gout; pseudogout; Paget's disease; joint fracture; acromegaly; fibromyalgia; Wilson's disease; ochronosis; haemochromatosis; osteochondromatosis; or collagen gene mutations.
Evidence of effusion greater than 15 cc upon physical examination of the joint at Baseline (Visit 1).
BMI greater than or equal to 38.
Major illness, requiring hospitalization during the 3 months before commencement of the screening period.
Unwillingness to stop taking pain medication (for arthritis or other types of pain) or was unwilling to stop taking other medications for the treatment of OA.
Previous failure or discontinuation (due to adverse events) of tramadol HCl therapy.
Treatment within the last 3 weeks with any of the following medications: monoamine oxidase inhibitors; tricyclic antidepressants and other tricyclic compounds (e.g. cyclobenzaprine, promethazine); neuroleptics; selective serotonin reuptake inhibitors; or any other drug that reduces seizure threshold.
Treatment with another investigational agent within the last 30 days.
A history of seizure disorder other than Infantile Febrile Seizures.
Previous or current opioid dependency.
Bowel disease causing malabsorption.
Pregnancy or lactating or childbearing potential and unwilling to utilize a medically approved method of contraception during participation in this clinical trial.
Significant liver disease, defined as active hepatitis or elevated liver enzymes >3 times the upper boundary of the normal range.
Significant renal disease, defined as creatinine clearance <30 mL/min as estimated by the method of Levey et al., 1999.
Current substance abuse or dependence, other than nicotine.
Allergy or adverse reaction to tramadol or any structurally similar drugs e.g. opiates.
Any other condition that, in the opinion of the Investigators, would have adversely affected the patient's ability to complete the study or its measures.
12. IPD Sharing Statement
Citations:
PubMed Identifier
18181382
Citation
Fishman RL, Kistler CJ, Ellerbusch MT, Aparicio RT, Swami SS, Shirley ME, Jain AK, Fortier L, Robertson S, Bouchard S. Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid OAD). J Opioid Manag. 2007 Sep-Oct;3(5):273-80. doi: 10.5055/jom.2007.0015.
Results Reference
result
Links:
URL
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=9048
Description
Approved labelling
Learn more about this trial
A Four-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol Once a Day 100, 200 and 300 mg Versus Placebo for the Treatment of Pain Due to Osteoarthritis of the Knee (With 7-Day Follow-up)
We'll reach out to this number within 24 hrs