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Toward Better Outcomes in Osteoarthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00000425
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : May 3, 2013
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Stanford University

Brief Summary:
This study will determine if there is a difference between commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (a pain-reliever that does not prevent inflammation) for treating knee pain in osteoarthritis (OA). The two main results we will look at are disease progression according to x-rays and disability over 3.5 years. Study participants with moderate knee OA and knee pain will continue taking their NSAID or stop taking their NSAID and start taking acetaminophen. Every 6 months we will send the participants questionnaires that ask about pain, medication use, and disability. We will take x-rays of the knees at the start of the study and again at the end of the study.

Condition or disease Intervention/treatment Phase
Osteoarthritis Drug: Nonsteroidal anti-inflammatory drugs (NSAIDs) Drug: Acetaminophen Phase 3

Detailed Description:

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular agents used to treat the joint pain and inflammation associated with OA. Although NSAIDs are useful for pain management, recent studies have not found NSAIDs to be better than acetaminophen for the treatment of painful knee OA. The relative lack of efficacy and possibility of accelerated disease progression, coupled with the known gastrointestinal risks of these medications, especially to the elderly, have led us to reevaluate NSAIDs as the first-line medical therapy for osteoarthritis. Our dominant NSAID-based approach to this disease may be resulting in unnecessary costs, unnecessary toxicity, and accelerated disability.

These data allow us to hypothesize that NSAIDs, by inhibiting pain and inflammation in osteoarthritic joints, may cause or encourage people with OA to overuse damaged joints, resulting in accelerated joint degeneration and joint replacements at an earlier time or, alternatively, that treatment with NSAIDs may accelerate joint damage by altering cartilage metabolism and inhibiting joint healing. We further hypothesize that anti-inflammatory therapy with NSAIDs results in toxicities that lead to increased comorbidity and higher medical care use compared to analgesic therapy for OA.

The specific aims of our study are to determine if (1) nonsteroidal anti-inflammatory drug therapy accelerates joint degeneration compared to analgesic medications; and (2) nonsteroidal anti-inflammatory drug therapy results in greater comorbidity and higher medical care costs and use compared to simple analgesic medication. To accomplish these aims, we will randomize 200 people with knee OA and 200 people with hip OA, defined by a Kellgren and Lawrence x-ray grade of 2 or 3, currently on NSAIDs, to either NSAIDs at their current dose or acetaminophen up to 4000 mg/day for 4 years.

Primary outcome measures will be the rate of radiographic progression, and pain and disability in the two groups. Secondary outcome variables will include medical care use, time to joint replacements, and medication side-effect profiles. We will separately identify and describe those clinical, demographic, and radiographic variables that predict accelerated progression in each group by multivariate analyses. By these methods, we will determine the long-term outcome of NSAID therapy versus analgesic therapy for the treatment of clinical OA of the knee and hip. This information is critical to improving the outcome of a disease that is the principal cause of disability in the elderly.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 900 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Toward Better Outcomes in Osteoarthritis (OA): Finding the Appropriate Role for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Study Start Date : July 1996
Study Completion Date : April 2001

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Knee osteoarthritis
  • Moderate radiographic evidence by Kellgren and Lawrence grade 2-4
  • Knee pain > 20 on VAS pain scale

Exclusion Criteria:

  • Bilateral knee replacements
  • Unwillingness to take acetaminophen for pain relief

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00000425

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United States, California
San Francisco General Hospital
San Francisco, California, United States, 94110
Sponsors and Collaborators
Stanford University
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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Study Director: Nancy Lane, MD UCSF, Division of Rheumatology, SFGH
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Responsible Party: Stanford University Identifier: NCT00000425    
Other Study ID Numbers: P01 AR43584 Substudy 0003
P01AR043584 ( U.S. NIH Grant/Contract )
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: May 3, 2013
Last Verified: April 2013
Keywords provided by Stanford University:
Skeletal disorder
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Cartilage metabolism
Outcomes research
Additional relevant MeSH terms:
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Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents