Discontinuing NSAIDs in Veterans with Knee Osteoarthritis

患有膝骨关节炎的退伍军人停用非甾体抗炎药

基本信息

批准号：
8475972
负责人：
Liana Fraenkel
金额：
--
依托单位：
VA CONNECTICUT HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8475972
关键词：
Acetaminophen Address Adherence Ambulatory Care Facilities Analgesics Area Cardiovascular system Caring Chronic Chronic Disease Cognitive Therapy Communities Comorbidity Cost Savings Data Degenerative polyarthritis Disease Double-Blind Method Drug usage Education Eligibility Determination Enrollment Guidelines Health Hospitalization Hospitals Knee Osteoarthritis Life Lower Extremity Measures Medical Informatics Mental Depression Modality Morbidity - disease rate Non-Steroidal Anti-Inflammatory Agents Ontario Pain Pain Research Patients Pharmaceutical Preparations Pharmacy facility Phase Phase I Clinical Trials Physicians Placebos Population Post-Traumatic Stress Disorders Protocols documentation Publishing Quality of Care Quality of life Randomized Recruitment Activity Research Design Risk Running Safety Sample Size Self Management Services Sleeplessness Study Subject Symptoms Telephone Testing Topical agent Toxic effect Transportation Universities Veterans Withdrawal alternative treatment arm base blind care delivery chronic pain clinically significant cost cost effectiveness design disability empowered evidence based guidelines experience follow-up gastrointestinal health economics high risk impression improved indexing innovation knee pain knee replacement arthroplasty meetings meloxicam mortality primary outcome programs secondary outcome

项目摘要

DESCRIPTION (provided by applicant): 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, we 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 12-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. We 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 16 weeks. We 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, we will perform both an intent to treat and per protocol analysis. Lastly, we 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, we 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 our 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.

描述（由申请人提供）：膝盖骨关节炎（OA）是退伍军人残疾的主要原因，是VA中膝盖替代的主要迹象。非甾体类抗炎药（NSAID）是膝盖OA最常见的药物。尽管短期研究表明，NSAID比安慰剂和对乙酰氨基酚更有效，但没有长期数据支持其使用。这是令人关注的，因为长期使用NSAID与显着的发病率和死亡率有关。已经发布了指南，以改善NSAID的安全使用；但是，在VA中，遵守这些基于证据的建议的依从性很低。因此，重要的是要确定NSAID的长期使用是否比更安全的替代方案提供任何增量益处。对于退伍军人来说尤其如此 NSAID引起的毒性的高风险。认知行为疗法（CBT）是OA的有效且安全的治疗方法。在VA中，这种方式越来越多，用于治疗慢性疼痛以及其他慢性疾病，例如抑郁症，创伤后应激障碍和失眠。 CBT可以通过电话成功管理，因此可以使居住在更偏远地区的退伍军人受益，而无法获得医院或基于社区的门诊诊所。在这项研究中，我们建议进行2期随机戒断试验（RWT）。该审判将着重于使用NSAID至少3个月的膝盖OA招募退伍军人。在研究的第一阶段中，有544名膝盖OA的退伍军人将被随机分配以继续NSAID或安慰剂4周。这个双盲阶段将使我们能够推断安慰剂是否不属于NSAID使用。在第二阶段，NSAIDS组的受试者将继续NSAID，安慰剂上的受试者将停止接受安慰剂并参加为期12周的CBT计划。第二个单盲阶段将使我们能够推断CBT是否不属于NSAID。所有研究数据都将通过电话收集，从而使他们能够安排向VA运输的退伍军人参加。我们将在4和16周（主要结局）测试使用经过验证的西安省和麦克马斯特大学骨关节炎指数（主要结局）测量的组间疼痛差异。我们还将测试下肢残疾的群体差异，受试者对变革的全球印象和使用疗法的使用（次要结果）。根据非效率试验的建议，我们将同时执行治疗和通过协议分析的意图。最后，我们将估计CBT协议与持续使用的CBT协议的潜在成本效益。尽管对于随机分配为活性研究药物的受试者继续其当前的NSAID是理想的选择，但使VA药房配制了多种不同的活性药物并保持盲人是不可能的。因此，我们将包括一个为期2周的跑步期，研究对象将用Meloxicam代替其NSAID。之所以选择Meloxicam作为研究药物，是因为它是我们中心最常见的处方，并且与其他NSAID相比具有良好的安全性。如果成功，该试验将提高因OA而患有慢性膝盖疼痛的退伍军人的护理质量。拟议的策略特别有吸引力，因为它可以用更安全的替代方案取代NSAID的广泛使用，从而可以向有限访问权限的退伍军人提供护理，并且可能会节省成本。