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|ClinicalTrials.gov Identifier: NCT01799213|
Recruitment Status : Active, not recruiting
First Posted : February 26, 2013
Last Update Posted : November 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Knee Osteoarthritis||Drug: Meloxicam 15 mg po QD Behavioral: Cognitive Behavioral Therapy||Phase 2|
Knee osteoarthritis (OA) is a major cause of disability among Veterans and is the primary indication of knee replacement in the VA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed medications for knee OA. Though short-term studies have demonstrated that NSAIDs are more effective than placebo and acetaminophen, there are no long-term data supporting their use. This is of concern, because long-term use of NSAIDs is associated with significant morbidity and mortality. Guidelines have been published to improve safe use of NSAIDs; however, adherence to these evidence-based recommendations is low in the VA. There is therefore an important need to determine if the long-term use of NSAIDs offers any incremental benefit over safer alternatives. This is especially true for Veterans, a population at high risk for NSAID-induced toxicity.
Cognitive behavioral therapy (CBT) is an effective and safe treatment alternative for OA. This modality is becoming increasingly available in the VA for treatment of chronic pain as well as other chronic disorders such as depression, post-traumatic stress disorder and insomnia. CBT can be successfully administered over the telephone and thus stands to benefit Veterans living in more remote areas with limited access to hospital or community-based outpatient clinics.
In this study, the investigators propose to conduct a 2-phase randomized withdrawal trial (RWT). The trial will focus on recruiting Veterans with knee OA who have been using NSAIDs for at least 3 months.
In the first phase of the study, 544 Veterans with knee OA will be randomized to continue NSAIDs or to placebo for 4 weeks. This double-blind phase will enable us to infer whether placebo is non-inferior to continued NSAID use. In the second phase, subjects in the NSAIDs group will continue NSAIDs and those on placebo will stop taking the placebo and participate in a 10-week CBT program. The second, single-blind, phase will allow us to infer whether CBT is non-inferior to NSAIDs. All study data will be collected over the telephone thus enabling Veterans who have difficulty arranging transportation to the VA to participate.
The investigators will test for between-group differences in knee pain measured using the well-validated Western Ontario and McMaster Universities Osteoarthritis Index (primary outcome) at 4 and 14 weeks. The investigators will also test for between group differences in lower extremity disability, subjects' global impression of change and use of co-therapies (secondary outcomes). As recommended for non-inferiority trials, the investigators will perform both an intent to treat and per protocol analysis. Lastly, the investigators will estimate the potential cost-effectiveness of the CBT protocol compared with continued NSAID use.
Though it would be ideal for subjects randomized to the active study drug to continue their current NSAID, having the VA pharmacy formulate multiple different active drugs and maintaining the blind is not possible. Therefore, the investigators will include a 2-week run-in period where study subjects will replace their NSAID with meloxicam. Meloxicam was chosen as the study drug because it is the most commonly prescribed at the investigators' center and has a favorable safety profile compared to other NSAIDS.
If successful, the trial will improve the quality of care delivered to Veterans with chronic knee pain due to OA. The proposed strategy is particularly appealing because it replaces the widespread use of NSAIDs with a safer alternative, enables delivery of care to Veterans with limited access, and is likely to be cost saving.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||680 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Discontinuing NSAIDs in Veterans With Knee Osteoarthritis|
|Actual Study Start Date :||September 2, 2013|
|Actual Primary Completion Date :||October 5, 2018|
|Estimated Study Completion Date :||December 31, 2018|
Experimental: Active Treatment
Eligible subjects will be randomized to Meloxicam 15 mg po QD vs placebo
Drug: Meloxicam 15 mg po QD
Eligible subjects will be take Meloxicam 15 mg po QD
Placebo Comparator: Placebo
Eligible subjects will be randomized to Meloxicam 15 mg po QD vs placebo
Behavioral: Cognitive Behavioral Therapy
Subjects originally assigned to placebo will receive cognitive behavioral therapy for 10 weeks
- The primary endpoint will be between-group differences in the WOMAC pain score (Likert Scale version) measured at 4 weeks. [ Time Frame: 4 Weeks ]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.
- Area under the curve (AUC) of the WOMAC pain scale score over the observation period: AUC will be measured in order to capture the variability in pain that is characteristic of knee OA . [ Time Frame: 14 Weeks ]As above
- Intermittent vs. Constant Pain [ Time Frame: Weekly ]Measure of Intermittent and Constant Osteoarthritis Pain will be used to evaluate the subject's pain experience, including pain intensity, frequency, as well as impact on mood, sleep, and quality of life. This 11-item scale asks subjects to rate their "constant knee pain" and their "knee pain that comes and goes" over the past week. Each item is scored on a scale from 0 to 4, with higher scores indicating a worse pain experience. The Intermittent and Constant Osteoarthritis Pain (ICOAP) complements the WOMAC given that the latter focuses on the impact of pain on physical functioning.
- Lower extremity disability [ Time Frame: 4 and 14 weeks ]Lower extremity disability: Lower extremity functional outcomes will be measured using the WOMAC disability scale. The physical disability scale contains 17 items that assess the amount of difficulty subjects say they have with climbing stairs, rising from a chair, walking, and other activities of daily living. Responses are measured and scored in the same way as the pain scale.
- Global impression of change [ Time Frame: 4 and 14 weeks ]A balanced 5-point scale (1 = Much better to 5 = Much worse) asking subjects to rate their change (if any) in pain since starting the study.
- Adherence to study medication and use of co-therapies [ Time Frame: Weekly ]
- Over the past week, how many days did you use the study drug for your knee pain?
- Over the past week, how many days did you use Tylenol or acetaminophen for your knee pain?
- Over the past week, how many days did you use other medications that were prescribed by one of your doctors for your knee pain?
- Over the past week, how many days did you use other medications, creams or supplements that you got without a prescription for your knee pain?
- Over the past week, how many days did you use any medications for a different problem or type of pain (e.g. headache)?
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 ClinicalTrials.gov identifier (NCT number): NCT01799213
|United States, Connecticut|
|VA Connecticut Healthcare System West Haven Campus, West Haven, CT|
|West Haven, Connecticut, United States, 06516|
|United States, Florida|
|North Florida/South Georgia Veterans Health System, Gainesville, FL|
|Gainesville, Florida, United States, 32608|
|United States, Massachusetts|
|VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA|
|Boston, Massachusetts, United States, 02130|
|United States, Rhode Island|
|Providence VA Medical Center, Providence, RI|
|Providence, Rhode Island, United States, 02908|
|Principal Investigator:||Liana Fraenkel, MD MPH FRCPC||VA Connecticut Healthcare System West Haven Campus, West Haven, CT|