Discontinuing NSAIDs in Veterans With Knee Osteoarthritis

NCT01799213 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IIR 11-113
• Study Type: interventional
• Target: 490
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

Knee Osteoarthritis

Keywords

Knee Osteoarthritis; NSAID; Cognitive Behavioral Therapy

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: WOMAC Pain Score (Likert Scale Version) at 4 Weeks

  The WOMAC pain score has a possible score range of 0-20 for Pain and higher scores indicate worse pain. The WOMAC pain scale consists of 5 questions that ask about pain during walking, stair use, lying in bed at night, sitting, and standing. Each question is scored on a 5-point scale, where 0 = None, 1 = Mild pain, 2 = Moderate pain, 3 = Severe pain, and 4 = Very severe pain. Total pain scores range from 0 to 20 with higher scores reflecting worse pain. The WOMAC also includes a lower extremity disability scale. Both the pain scale and disability scale (17 items) can be analyzed separately.

  4 Weeks

Secondary Outcomes (5)

• Area Under the Curve (AUC) of the WOMAC Pain Scale Score Over 14 Weeks

  14 Weeks

• Lower Extremity Disability

  14 weeks

• Global Impression of Change

  14 weeks

• Adherence to Study Medication (Assessed in Weeks Adherent)

  Weekly, for duration of observation period (14 weeks)

• Adherence to Study Medication (Assessed in % of Weeks With Perfect Adherence)

  Weekly, for duration of observation period (14 weeks)

Study Arms (2)

Active Treatment

EXPERIMENTAL

Eligible subjects will be randomized to Meloxicam 15 mg po per day (QD) vs placebo

Drug: Meloxicam 15 mg po QD

Placebo

PLACEBO COMPARATOR

Eligible subjects will be randomized to Meloxicam 15 mg po QD vs placebo

Behavioral: Cognitive Behavioral Therapy

Interventions

Meloxicam 15 mg po QD DRUG

Eligible subjects will be take Meloxicam 15 mg po QD

Active Treatment

Cognitive Behavioral Therapy BEHAVIORAL

Subjects originally assigned to placebo will receive cognitive behavioral therapy for 10 weeks

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (4)

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, 06516-2770, United States

Location

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, 32608-1135, United States

Location

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130, United States

Location

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908, United States

Location

Related Publications (2)

• Goulet JL, Buta E, Brennan M, Heapy A, Fraenkel L. Discontinuing a non-steroidal anti-inflammatory drug (NSAID) in patients with knee osteoarthritis: Design and protocol of a placebo-controlled, noninferiority, randomized withdrawal trial. Contemp Clin Trials. 2018 Feb;65:1-7. doi: 10.1016/j.cct.2017.11.020. Epub 2017 Dec 2.

  PMID: 29198731 BACKGROUND

• Fraenkel L, Buta E, Suter L, Dubreuil M, Levy C, Najem C, Brennan M, Corn B, Kerns R, Goulet J. Nonsteroidal Anti-inflammatory Drugs vs Cognitive Behavioral Therapy for Arthritis Pain: A Randomized Withdrawal Trial. JAMA Intern Med. 2020 Sep 1;180(9):1194-1202. doi: 10.1001/jamainternmed.2020.2821.

  PMID: 32702101 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Meloxicam; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Thiazines; Sulfur Compounds; Organic Chemicals; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Lisa G. Suter, MD
• Organization: Veterans Health Administration, West Haven, CT

lisa.suter@va.gov; lisa.suter@yale.edu

2039325711

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2013
• First Posted: February 26, 2013
• Study Start: September 2, 2013
• Primary Completion: October 5, 2018
• Study Completion: October 5, 2018
• Last Updated: July 27, 2023
• Results First Posted: December 16, 2019

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)