Toward Better Outcomes in Osteoarthritis
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): Nonsteroidal anti-inflammatory drugs (NSAIDs); Acetaminophen
Intervention type(s): Drug; Drug
Intervention MeSH terms: Acetaminophen; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Osteoarthritis; Skeletal disorder; Chemotherapy; Nonsteroidal anti-inflammatory drugs (NSAIDs); Arthroplasty; Cartilage metabolism; Hip; Knee; Outcomes research