Discontinuing NSAIDs in Veterans With Knee Osteoarthritis
Condition: Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Meloxicam 15 mg po QD; Cognitive Behavioral Therapy
Intervention description: Eligible subjects will be take Meloxicam 15 mg po QD; Subjects originally assigned to placebo will receive cognitive behavioral therapy for 10 weeks
Intervention MeSH terms: Meloxicam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 490.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Knee Osteoarthritis; NSAID; Cognitive Behavioral Therapy

Summary:

      Knee osteoarthritis (OA) is now recognized as a major health problem. It is the number one
      cause of lower extremity disability and has significant deleterious effects on quality of
      life. While there are numerous therapies available for knee OA, most have limited efficacy.
      Of particular concern, is the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs)
      for this disorder. Veterans, as a group, are at high risk for both gastrointestinal and
      cardiovascular NSAID-induced complications. In this study the investigators propose to
      examine whether replacing NSAIDs with cognitive behavioral therapy delivered by telephone is
      an effective strategy for Veterans with knee OA. Telephone-administered therapy is
      particularly appealing since Veterans with knee OA are more likely to have limited mobility.
      If successful, this program may result in significant cost-savings for both Veterans
      (decreased co-pays and transportation costs) and the VA (decreased hospitalizations due to
      NSAID induced toxicity).
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects will include those for whom a discontinuation trial of NSAIDs is most appropriate:
        1) Veterans with knee pain despite NSAID use and/or 2) Veterans at relatively higher risk
        of NSAID toxicity 55-59 as ascertained by meeting 1 or more of the following 4 criteria:

          -  Answer affirmatively to the question: "Do you have some knee pain on most days over
             the past 3 months?"

          -  Have 1 or more risk factors for NSAID-induced nephrotoxicity (age greater than 60
             years, atherosclerotic cardiovascular disease, current diuretic use, chronic renal
             insufficiency, congestive heart failure (New York Heart Association class I-II. Note,
             Class III and IV are excluded).

          -  Have 1 or more risk factors for NSAID-induced gastrointestinal toxicity (history of
             peptic ulcer disease, age > 65 years, concurrent use of daily ASA or corticosteroids),
             and are currently on a gastro-protective agent.

          -  Have 1 or more risk factors for NSAID-induced cardiovascular toxicity (prevalent
             cardiovascular disease, hypertension, hypercholesterolemia, diabetes, smoking, family
             history of early heart disease or age greater than 55 years for women).

        In addition, subjects must:

          -  Be age 20 years or older. While the usual cut off for knee OA is approximately 40
             years, the investigators chose to lower the age cutoff as younger Veterans have a
             higher than expected risk of OA (see B.1).

          -  Have radiographic evidence of knee OA reported in the VistA electronic system.

          -  Be using an NSAID (other than daily ASA) for knee pain on most days of the month for
             at least the past 3 months.

          -  Be able to understand and speak English and have a telephone.

          -  Be willing to engage in a CBT program, to discontinue (or replace) their NSAID, and to
             restrict co-therapies to acetaminophen for 14 weeks.

        Exclusion Criteria:

          -  Subjects desiring escalation of analgesics for their current level of knee pain as
             determined by endorsement of the following statement: "Is your knee pain bad enough
             that you want to talk to your doctor about taking stronger pain medications?"

          -  Current use of opioids and/or Celebrex.

          -  Current use of an NSAID (not including ASA) for a painful condition in addition to
             knee OA.

          -  Contraindications to chronic NSAID use: current use of warfarin or antiplatelet agent
             other than ASA, allergy to any NSAID, active upper gastrointestinal ulceration in the
             previous 30 days, upper gastrointestinal bleeding in the past year, history of
             gastroduodenal perforation or obstruction, cardiovascular event within the past 6
             months (myocardial infarction, cerebrovascular event, coronary-artery bypass graft,
             invasive coronary revascularisation, or new-onset angina), severe congestive heart
             failure (New York Heart Association class III-IV), evidence of serious anemia,
             hepatic, renal (including nephrotic syndrome), or blood coagulation disorders, and
             pregnancy.

        ***Though the investigators are proposing a RWT - and thus will not be initiating NSAID
        therapy - it would not be appropriate to continue NSAIDs (even when prescribed) in
        high-risk patients. The investigators acknowledge that these exclusion criteria limit
        generalizability, but the investigators feel justified to ensure subjects' safety.***

          -  Previous hyaluronic acid knee injections (within 6 months) or corticosteroid knee
             injections (within 3 months).

          -  Scheduled knee hyaluronic acid or corticosteroid injections, arthroscopy, or knee
             surgery.

          -  Co-morbid conditions that include the following: known other causes of arthritis
             (infectious arthritis, rheumatoid arthritis, connective tissue disease, or psoriatic
             arthritis), gout or pseudogout attack within the last 12 months, peripheral neuropathy
             or cardiopulmonary disease that limits walking more than knee pain, bone metastases or
             Paget's disease involving the lower extremities, and history of drug or alcohol abuse
             within the past 2 years, bilateral knee replacements or knee pain in the replaced knee
             only.

          -  Current involvement in litigation or receiving workmen's compensation.

          -  Hearing, cognitive impairment or mental illness, as determined by chart review that
             would preclude participation in a CBT program.

          -  For Women of Childbearing Age: Must not currently be pregnant, agree to avoid getting
             pregnant during the course of the study and should inform the study team if pregnancy
             occurs at any time during study participation.

          -  Previous meloxicam use discontinued due to lack of effective symptom relief

          -  Contraindications to prolonged NSAID use, per PI discretion.