A Comparative Study of Tramadol Hydrochloride Plus Acetaminophen Tablets Maintenance Versus Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Maintenance in Participants With Knee Osteoarthritis

A Comparison of Tramadol/Acetaminophen Tablets Maintenance Versus NSAID Maintenance After Tramadol/Acetaminophen and NSAID Combination Therapy in Knee Osteoarthritis Patients: Multicenter, Randomized, Open Comparative Study

The purpose of this study is to compare the effectiveness of tramadol hydrochloride 37.5 milligram (mg) plus acetaminophen 325 mg maintenance with that of non-steroidal anti-inflammatory drugs (NSAIDs) maintenance in participants with knee osteoarthritis (a progressive and degenerative joint disease, in which the joints become painful and stiff) whose pain was relieved after the add-on treatment of tramadol hydrochloride to NSAIDs.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Meloxicam; Drug: Aceclofenac; Drug: Tramadol Hydrochloride Plus Acetaminophen

Detailed Description

This is a multicenter (when more than one hospital or medical school team work on a medical research study), randomized (the study drug is assigned by chance), open-label (all people know the identity of the intervention), comparative study to compare the efficacy of tramadol hydrochloride plus acetaminophen maintenance with that of NSAIDs maintenance in participants whose pain was relieved after the add-on treatment of tramadol 37.5 milligram (mg) plus acetaminophen 325 mg to NSAIDs. All participants will receive tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day along with NSAIDs (meloxicam [7.5 mg or 15 mg once daily] or aceclofenac [100 mg twice daily]) from Day 1 to Day 28, and participants will be randomly assigned into 2 treatment groups at Day 29 if the numerical rating scale score less than or equal 4. Tramadol plus acetaminophen group will receive 1 or 2 tablets containing tramadol 37.5 mg plus acetaminophen 325 mg 4 times daily (maximum daily dose will be 8 tablets) from Day 29 to Day 85 and NSAIDs group will receive either meloxicam 7.5 mg or 15 mg per day or aceclofenac 100 mg twice a day from Day 29 to Day 85. The efficacy will be evaluated on Day 1, Day 29, Day 57 and Day 85. The primary efficacy end point will be assessed through change in Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) total score from Day 29 to Day 85. Participant's safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants who have suffered from knee osteoarthritis at least for one year and meet the criteria of American College of Rheumatology
• Participants who are taking stable dose of meloxicam 7.5 milligram (mg) or 15 mg daily or aceclofenac 100 mg twice a day at least for four weeks
• Participants whose mean pain intensity has been 5 or higher on the numeric rating scale (NRS) for the last 48 hours
• Participants whose general health conditions are favorable, according to the criteria below: Medical and medication history, Physical examination before the study medication administration, Vital signs: Blood pressure, pulse, Clinical laboratory tests: Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvate transaminase (SGPT) less-than or equal to (=<) 2 X normal range, Renal function: Creatinine less than (<) 2.0 milligrams per deciliter (mg/dl)
• Female participants of childbearing potential to use the proper contraceptive methods during the study period (Urine pregnancy test prior to the study participation should be negative)

Exclusion Criteria:

• Participants who are applicable to Kellgren and Lawrence grade
• Participants who had failed tramadol treatment before or stopped taking tramadol due to adverse event(s)
• Participants who are applicable to one of the following conditions: Rheumatoid arthritis, Ankylosing spondylitis, Active gout or active pseudo-gout, Diagnosis of fibromyalgia (according to ACR Criteria), Anserine bursitis, Major trauma of the target joint within six months prior to the study medication administration, Infection of the target joint within six months prior to the study medication administration, Apparent avascular necrosis of the target joint within six months prior to the study medication administration, Anatomical deformities of the target joint, which may interfere with assessment of the target joint, Surgical procedures associated with the target joint within one year prior to the study medication administration, Arthroscopic procedures associated with the target joint within six months prior to the study medication administration
• Participants who have one of the following diseases: Significantly unstable diseases such as sleep disorder (e.g., sleep apnea or narcolepsy) or dementia, Functional damage or disease which may cause malabsorption, excessive accumulation, or metabolism or excretion disorder
• Participants who are pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Non-steroidal Anti-inflammatory Drug (NSAIDs); Participants will receive fixed dose combination of tramadol hydrochloride 37.5 milligram (mg) plus acetaminophen 325 mg, 1 to 3 tablets per day along with meloxicam (7.5 mg or 15 mg once daily) or aceclofenac (100 mg twice daily) from Day 1 to Day 28. Participants who will have the numeric rating scale score 4 or less on Day 29 will be randomly assigned to the treatment of NSAIDs to receive either meloxicam (7.5 mg or 15 mg once daily) or aceclofenac (100 mg twice daily) from Day 29 to Day 85.	Drug: Meloxicam; Meloxicam 7.5 mg or 15 mg per day along with fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day from Day 1 to Day 28, and meloxicam 7.5 mg or 15 mg per day from Day 29 to Day 85.; Drug: Aceclofenac; Aceclofenac 100 mg twice a day along with fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day from Day 1 to Day 28, and aceclofenac 100 mg twice a day from Day 29 to Day 85.; Drug: Tramadol Hydrochloride Plus Acetaminophen; Fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day along with NSAIDs (meloxicam [7.5 mg or 15 mg once daily] or aceclofenac [100 mg twice daily]) from Day 1 to Day 28, and fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 or 2 tablets 4 times daily from Day 29 to Day 85 (maximum daily dose will be 8 tablets).
Experimental: Tramadol Hydrochloride Plus Acetaminophen; Participants will receive fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day along with meloxicam (7.5 mg or 15 mg once daily) or aceclofenac (100 mg twice daily) from Day 1 to Day 28. Participants who will have the numerical rating scale score 4 or less on Day 29 will be randomly assigned to the treatment of fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 or 2 tablets 4 times daily from Day 29 to Day 85 (maximum daily dose will be 8 tablets).	Drug: Meloxicam; Meloxicam 7.5 mg or 15 mg per day along with fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day from Day 1 to Day 28, and meloxicam 7.5 mg or 15 mg per day from Day 29 to Day 85.; Drug: Aceclofenac; Aceclofenac 100 mg twice a day along with fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day from Day 1 to Day 28, and aceclofenac 100 mg twice a day from Day 29 to Day 85.; Drug: Tramadol Hydrochloride Plus Acetaminophen; Fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 to 3 tablets per day along with NSAIDs (meloxicam [7.5 mg or 15 mg once daily] or aceclofenac [100 mg twice daily]) from Day 1 to Day 28, and fixed dose combination of tramadol hydrochloride 37.5 mg plus acetaminophen 325 mg, 1 or 2 tablets 4 times daily from Day 29 to Day 85 (maximum daily dose will be 8 tablets).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Day 29 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score at Day 85	The WOMAC is a self-administered and health status questionnaire designed to capture elements of pain, stiffness and physical impairment in participants with osteoarthritis. It consists of 24 questions (5 questions about pain, 2 about stiffness and 17 about physical function) scored on a visual analog scale (VAS) of 0 to 10 cm (0 cm=no pain to 10 cm=worse pain). Individual question responses are assigned a score between 0=extreme and 4=none. Maximum scores for each element differ and therefore, scores were normalized. Total normalized score ranges from 0=worst to 100=best.	Day 29 and Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Day 29 in Pain Intensity Score at Day 85	Pain intensity was evaluated by 11- point numeric rating scale ranging from 0 to 10 where, 0=no pain and 10=pain as bad as you can imagine.	Day 29 and Day 85
Number of Participants With Pain Relief	Pain relief was assessed by using a 6-point scale ranging from -1 to 4 where, -1=pain aggravated, 0=no change, 1=slightly relieved, 2=moderately relieved, 3=considerably relieved, and 4=pain completely disappeared. Participants with pain slightly relieved, moderately relieved and completely disappeared were considered as pain relieved.	Day 29, Day 57 and Day 85
Number of Participants With Overall Assessment on Study Drug by Participants	Participants' overall assessment on study drug was done by using a 5-point scale ranging from -2 to 2 where, -2= very bad, 1= bad, 0=moderate, 1=good and 2=very good. Study drug refers specifically to the randomized treatment received from Day 29 to Day 85.	Day 85
Number of Participants With Overall Assessment on Study Drug by Investigator	Investigator was completed overall assessment on study drug by using a 5-point scale (-2 to 2; where, -2= very bad, 1= bad, 0=moderate, 1=good and 2=very good). Study drug refers specifically to the randomized treatment received from Day 29 to Day 85.	Day 85
Number of Participants With Categorical Swelling	Swelling was assessed by using a 4-point scale ranging from 0 to 3 where, 0=no swelling, 1=presence of cross fluctuation of fluid (PCFF), 2=patellar ballotment, and 3=swelling that distort the joint contours (SDJC).	Day 29, Day 57 and Day 85
Number of Participants With Categorical Tenderness	Tenderness was assessed by using a 4-point scale 0 to 3 where, 0= no tenderness, 1= complaint of tenderness, 2=complaint of tenderness with wincing (CTW), and 3=wincing and attempt to withdraw.	Day 29, Day 57 and Day 85

Collaborators and Investigators

• Sponsor: Janssen Korea, Ltd., Korea

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: March 6, 2008
• First Submitted That Met QC Criteria: March 6, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Estimate): July 22, 2013
• Last Update Submitted That Met QC Criteria: July 16, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: WOMAC; Acetaminophen; Tramadol; Meloxicam; Pain intensity; Knee osteoarthritis pain; Aceclofenac
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Cyclooxygenase 2 Inhibitors; Acetaminophen; Tramadol; Meloxicam; Aceclofenac
• Other Study ID Numbers: CR012964; NCT00635349; ULT-KOR-05