Clinical trial: Discontinuing NSAIDs in Veterans With Knee Osteoarthritis (NCT01799213)

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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 20 Years old.


Patient description (medical language): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient description (patient's own words): I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Does the patient match the trial criteria? Contradiction