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 Overview
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Brief Summary
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The objective of this study is to compare the analgesic efficacy and safety of Tramadol Once a Day 100, 200, 300 mg and Placebo

Conditions
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Pain

Intervention / Treatment
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* Drug: Tramadol Once A Day
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: Tramadol Once A Day 100mg<br> | Drug: Tramadol Once A Day<br>* One Tramadol Once A Day tablet at randomized dose daily.<br>|
| Experimental: 2: Tramadol Once A Day 200mg<br> | Drug: Tramadol Once A Day<br>* One Tramadol Once A Day tablet at randomized dose daily.<br>|
| Experimental: 3: Tramadol Once A Day 300mg<br> | Drug: Tramadol Once A Day<br>* One Tramadol Once A Day tablet at randomized dose daily.<br>|
| Placebo Comparator: 4: Placebo<br> | Drug: Placebo<br>* One Placebo tablet daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks | 
| 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. | 12 weeks | 
| 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 0, week 3, week 6 | 
| 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). | Week 0, week 3, week 6 | 
| 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). | 12 weeks | 
| 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. | 12 weeks | 
| Dropout Rate | Reasons for withdrawal from the trial were collected | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain due to Osteoarthritis of the Knee