A Sequenced Strategy for Improving Outcomes in People With Knee Osteoarthritis Pain
概览
- 阶段
- 3 期
- 干预措施
- Duloxetine
- 疾病 / 适应症
- Knee Osteoarthritis
- 发起方
- Johns Hopkins University
- 入组人数
- 1937
- 试验地点
- 29
- 主要终点
- Change in Pain Intensity as assessed by the Modified 4-item Brief Pain Inventory (BPI) Pain Scale
- 状态
- 已完成
- 最后更新
- 23天前
概览
简要总结
There is an urgent public health need to reduce reliance on opioids for effective long-term pain management, particularly in knee osteoarthritis (KOA). This effectiveness trial will compare commonly recommended treatments to reduce pain and functional limitations in KOA.These results will lead to improved patient selection for treatment and inform evidence based guidelines by offering well-tested, effective, non-surgical alternatives.
详细描述
Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability worldwide, affecting over 30% of older adults. It represents a major global health and economic burden to individuals and society. The rates of KOA have more than doubled in the past 70 years and continue to grow sharply, given increases in life expectancy and population body mass index (BMI). Surgery is often employed to treat KOA, but it is associated with a high rate of persistent pain, and is not a permanent solution. Numerous nonsurgical therapies have been advocated to treat pain in patients with KOA yet are not often used in clinical care. The limited pain relief and functional improvement seen in a subset of knee OA sufferers has led to a high rate of opioid use and disability in this population. The overarching goal of this study is to conduct a sequential parallel group randomized controlled trial (RCT) to evaluate the comparative effectiveness of conservative behavioral and non-opioid pharmacological treatments (Phase 1) and, among those that indicate interest in obtaining further treatment and those not eligible for conservative treatment, the benefits of procedural interventions (Phase 2). This study will also evaluate whether clinical and psychosocial phenotypes predict short- and longer-term treatment response. The results of this study will examine the effectiveness of each tested intervention and provide meaningful information regarding effectiveness across key subgroups of participants.
研究者
入排标准
入选标准
- •Knee pain score of ≥4 and ≤ 9 on the Modified 4-Item BPI Pain Scale at pre-intervention screening
- •Meets at least 1 of the 3 American College of Rheumatology (ACR) Classification criteria for knee osteoarthritis.
- •ACR criteria are:
- •At least three of the following using history and physical examination: age \>50 years old; morning stiffness \<30 minutes; crepitus on knee motion; bony tenderness; bony enlargement; no palpable warmth
- •At least one of the following using history, physical examination, and radiographic findings + the presence of osteophytes: age \>50 years old; morning stiffness \<30 minutes; crepitus on active motion and osteophytes
- •At least 5 of the following using history, physical examination, and laboratory findings: age \>50 years old; morning stiffness \<30 minutes; crepitus on knee motion; bony tenderness; bony enlargement; no palpable warmth; erythrocyte sedimentation rate (ESR) \<40 mm/hour; Rheumatoid Factor (RF) \<1:40; synovial fluid signs of osteoarthritis
排除标准
- •\<18 years of age
- •Any inability to complete study procedures, including, but not limited to inadequate resources to mitigate low English language literacy
- •Refusal of randomization
- •Knee pain exclusions: Pain during an average of \< 4 days per week over the past 3 months; pain in the index knee from a joint disease other than OA (e.g., infectious arthritis, rheumatoid arthritis, spondyloarthropathy)
- •Medication exclusions: Report changes in analgesic medication dose within 2 weeks of baseline; oral morphine equivalent dose of \> 90 mg/d at baseline
- •Medical condition exclusions: Severe vision or hearing impairment or any signs of cognitive impairment that would prevent comprehension of consent procedures, study measures, or procedures; unstable medical condition that presents an absolute or relative contraindication for participation in both arms (e.g., unstable angina, congestive heart failure); poorly controlled serious psychiatric condition that could prevent full participation or affect outcomes (e.g., suicidal ideation, active psychosis, poorly controlled depression, active substance abuse \[excluding tobacco, caffeine or moderate alcohol use\])
- •Knee-specific medical condition exclusions: History of bilateral knee joint replacement arthroplasty total knee arthroplasty (TKA) or TKA in the affected knee; partial replacements may be eligible depending on physician judgment; scheduled joint replacement; history of unilateral TKA and complaints of KOA pain limited to the operated knee; Intra-articular viscosupplementation, steroid injection or arthroscopic surgery in the index knee within 12 weeks of baseline
- •Pregnancy by self-report, report of intention to become pregnant (Phase 1), or as determined by urine pregnancy screening (if Standard of Care at site) (Phase 2). Due to the unknown effects of duloxetine on the developing fetus and newborn, and the potential harms of fluoroscopy in pregnancy, women who are pregnant or lactating or intend to get pregnant will not be included in this study. Those of childbearing potential will be asked to use reliable contraception during the course of their participation in the study and to notify the study team if they become pregnant during participation. Definition of reliable birth control will be defined as: Female and male sterilization (female tubal ligation or occlusion, male vasectomy); long-acting reversible contraceptives (LARC) methods (intrauterine devices, hormonal implants); short-acting hormonal methods (pill, mini pills, patch, shot, vaginal ring); barrier methods (condoms, diaphragms, sponge, cervical cap)
- •Phase 1 specific Exclusion Criteria- An individual who meets any of the following criteria will be excluded from participation in Phase 1 of this study and will be enrolled and randomized directly into Phase 2:
- •Known allergic reaction or medical condition that renders an individual unsuitable for Phase 1 study interventions, including closed-angle glaucoma, kidney disease (creatinine clearance \< 30 mL/ min), severe liver disease, known adverse reaction to duloxetine or another selective serotonin-norepinephrine reuptake inhibitor (SNRI), bipolar disorder or mania, high likelihood of drug interactions that could lead to side effects (e.g., serotonin syndrome in people on multiple drugs that inhibit serotonin reuptake including monoamine oxidase (MAO) inhibitors).
研究组 & 干预措施
Phase 1: Best Practices + Duloxetine
Participants will receive Duloxetine and a prescription for guideline-recommended treatments for knee osteoarthritis, i.e., Best Practices. Best Practices can include topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen; physical therapy that may include aquatherapy; integrative treatments such as acupuncture, yoga, or a structured exercise program; and other non-invasive treatments. Phase 1 ended enrollment on April 12, 2024.
干预措施: Duloxetine
Phase 1: Best Practices + Duloxetine
Participants will receive Duloxetine and a prescription for guideline-recommended treatments for knee osteoarthritis, i.e., Best Practices. Best Practices can include topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen; physical therapy that may include aquatherapy; integrative treatments such as acupuncture, yoga, or a structured exercise program; and other non-invasive treatments. Phase 1 ended enrollment on April 12, 2024.
干预措施: Best Practices
Phase 1: Best Practices + Duloxetine + Pain coping skills
Participants will receive Duloxetine, pain coping skills training, and a prescription for guideline-recommended treatments for knee osteoarthritis, i.e., Best Practices. Best Practices can include topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen; physical therapy that may include aquatherapy; integrative treatments such as acupuncture, yoga, or a structured exercise program; and other non-invasive treatments. Phase 1 ended enrollment on April 12, 2024.
干预措施: Duloxetine
Phase 1: Best Practices + Duloxetine + Pain coping skills
Participants will receive Duloxetine, pain coping skills training, and a prescription for guideline-recommended treatments for knee osteoarthritis, i.e., Best Practices. Best Practices can include topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen; physical therapy that may include aquatherapy; integrative treatments such as acupuncture, yoga, or a structured exercise program; and other non-invasive treatments. Phase 1 ended enrollment on April 12, 2024.
干预措施: Pain Coping Skills Training
Phase 1: Best Practices + Duloxetine + Pain coping skills
Participants will receive Duloxetine, pain coping skills training, and a prescription for guideline-recommended treatments for knee osteoarthritis, i.e., Best Practices. Best Practices can include topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen; physical therapy that may include aquatherapy; integrative treatments such as acupuncture, yoga, or a structured exercise program; and other non-invasive treatments. Phase 1 ended enrollment on April 12, 2024.
干预措施: Best Practices
Phase 2: Intra-Articular Injection (HA+)
Participants will receive an intra-articular injection of hyaluronic acid mixed with steroid and bupivacaine. Phase 2 ended enrollment on October 24, 2024.
干预措施: Intra-Articular Injection
Phase 2: Nerve Procedure: Long Acting Blocks
Participants will receive a nerve blocking procedure, long-acting local anesthetic, and steroid injection. Phase 2 ended enrollment on October 24, 2024.
干预措施: Nerve Procedure with long acting blocks
Phase 2: Nerve Procedure: Nerve Ablation
Participants will receive a nerve ablation procedure and steroid injection. Phase 2 ended enrollment on October 24, 2024.
干预措施: Nerve Procedure with nerve ablation
Phase 1: Best Practices
Participants will receive a prescription for guideline-recommended treatments for knee osteoarthritis, i.e., Best Practices. Best Practices can include topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen; physical therapy that may include aquatherapy; integrative treatments such as acupuncture, yoga, or a structured exercise program; and other non-invasive treatments. Based on the pre-specified stopping rules described in Protocol section 13.2, the DSMB advised ceasing enrollment into Arm 1A (Best Practices). This recommendation was accepted by the sponsor and study investigators. Arm 1A (Best Practices) was closed on 11/29/2023.
干预措施: Best Practices
结局指标
主要结局
Change in Pain Intensity as assessed by the Modified 4-item Brief Pain Inventory (BPI) Pain Scale
时间窗: Change from Baseline to 8 weeks post-randomization (mITT) and to 8 weeks post-treatment (per protocol) in Phase 1; Change from Baseline to 12 weeks post-randomization (mITT) and to 12 weeks post-treatment (per protocol) in Phase 2
The Modified 4-item BPI Pain scale consists of 3 items from BPI Pain Intensity and 1 item from BPI Pain Interference. This is a continuous measure that will be calculated as the average of worst, average, current knee pain, and pain upon walking. Change from baseline (BL) will be used in mITT analyses, and change from treatment will be used in per protocol analyses.
次要结局
- Change in Physical Functioning as assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS)(Change from baseline to 8 weeks post-randomization (mITT) and to 8 weeks post-treatment (per protocol) in Phase 1; Change from Baseline to 12 weeks post-randomization (mITT) and to 12 weeks post-treatment (per protocol) in Phase 2)
- Compare Morphine Milligram Equivalent (MME) doses(Change from baseline to 8 weeks post-randomization (mITT) and to 8 weeks post-treatment (per protocol) in Phase 1; Change from baseline to 12 weeks post-randomization (mITT) and to 12 weeks post-treatment (per protocol) in Phase 2)
- Patient Global impression of Change (PGIC)(8 weeks post-randomization (mITT) and 8 weeks post-treatment (per protocol) in Phase 1; 12 weeks post-randomization (mITT) and 12 weeks post-treatment (per protocol) in Phase 2)
- Time to receipt of additional treatment for to KOA(Up to 2 years)
- Change in Pain Interference as assessed by the BPI(Change from Baseline to 8 weeks post-randomization (mITT) and to 8 weeks post-treatment (per protocol) in Phase 1; Change from Baseline to 12 weeks post-randomization (mITT) and to 12 weeks post-treatment (per protocol) in Phase 2)
- Change in Pain Intensity as assessed by the BPI(Change from baseline to 8 weeks post-randomization (mITT) and to 8 weeks post-treatment (per protocol) in Phase 1; Change from baseline to 12 weeks post-randomization (mITT) and to 12 weeks post-treatment (per protocol) in Phase 2)
- Treatment response as a binary outcome for Phase 1 and 2 intervention arms using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) guidelines(Opioid use and pain are measured at all follow-up time points and will be used through Phase1: 8 weeks post-rand. and 8 weeks post-treatment; Phase 2: 12 weeks post-rand. and 8 weeks post-treatment)
- Treatment response as a binary outcome for Phase 1 and 2 intervention arms based on OARSI-OMERACT guidelines, incorporating changes in opioid dose.(Opioid use and pain assessed up to 2 years. PGIC assessed at main outcome visit (8 and 12 weeks for Phase 1 and Phase 2, respectively). The treatment response categorical outcome will be analyzed separately for mITT and per- protocol analyses.)