Study design and protocol of a randomized, pragmatic, comparative effectiveness trial evaluating a sequenced strategy for improving outcomes in people with knee osteoarthritis pain (SKOAP): Conservative treatment evaluation
Year: 2025
Type: article
Study design: Study Protocol
Abstract: BACKGROUND: Treatment guidelines for knee osteoarthritis (KOA) vary across organizations, partly due to the lack of high-quality evidence. Experts disagree on the role of psychological management, pharmacologic treatments including opioids, and interventional therapies. METHODS/DESIGN: The Sequenced strategy for Knee OsteoArthritis Pain (SKOAP) trial is a multi-site, randomized, pragmatic clinical trial that uses a two-phase sequential design to evaluate the effectiveness of several interventions in individuals reporting KOA pain. Described here is the protocol for Phase 1 of the trial sequence which focuses on conservative treatments. All participants receive Best Practices (BP), a guideline-based approach to care that includes physical therapies, alternative treatments, and over-the-counter medications. Participants are then randomized to one of three groups: (1) BP alone, (2) BP plus duloxetine (30-120 mg/day), or (3) BP plus duloxetine and painTRAINER, a web-based, Cognitive Behavioral Therapy (CBT)-informed pain coping skills training. Phase 1 aims to determine whether the combination of duloxetine and BP improves pain compared to BP alone, and whether the combination of painTRAINER, duloxetine and BP provides additional benefit compared to duloxetine combined with BP. The analysis will include a modified Intention to Treat (mITT) approach and two Per-Protocol (PP) analyses; Receipt of Prescription (PP-ROP) and Minimum Effective Dose (PP-MinED). A third aim of Phase 1 is to identify clinical characteristics, patient-level factors, and psychosocial phenotypes that predict short- and long-term outcomes. DISCUSSION: Findings from Phase 1 of the SKOAP trial will provide evidence on the effectiveness of non-opioid pharmacologic and psychological interventions for the treatment of painful KOA beyond established best practices. It may also help refine personalized treatment strategies.
Authors: Heavon M. Allen, Melinda M. Holena, Lauren E. Allen, SiNing Zhao, Renan C. Castillo, Steven P. Cohen, Robert W. Hurley, Daniel O. Scharfstein, Jennifer A. Haythornthwaite, Srinivasa N. Raja, Stephen T. Wegener, Christine M. Rini, Francis J. Keefe, Jordan Bridges, Ron Reeder, Richard E. Thompson, Dan Hanley, Claudia M. Campbell
Institutions: Johns Hopkins University, Northwestern University, Atrium Health Wake Forest Baptist, Wake Forest University Health Sciences, Wake Forest University, University of Utah, Johns Hopkins Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Duke University, Duke Medical Center
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,370
Awards: G2267104472, Center for Innovative TRIals in ChilDrEN and AdulTs (TRIDENT), Johns Hopkins-Tufts Trial Innovation Center, A sequenced-strategy for improving outcomes in patients with knee osteoarthritis pain, Utah Trial Innovation Center, Improving Clinical trial Education, Recruitment, and Enrollment at CTSA Hubs (I-CERCH), Johns Hopkins Statistical and Safety Resource Center-HEAL PAIN ERN, ICERCH-Supporting the HEAL Pain ERN, HEAL Clinical Coordinating Resource Center for the Pain Management Effectiveness Research Network, HEAL ERN: Data Coordinating Resource Center
OpenAlex ID: W4414484833