# 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

## TL;DR

This study tests how adding medication and online therapy to standard care affects knee osteoarthritis pain.

## Contribution

The study introduces a sequenced trial design to evaluate non-opioid interventions for knee osteoarthritis pain.

## Key findings

- Combining duloxetine with standard care may improve pain outcomes.
- Adding online CBT training could provide additional benefits beyond medication.
- The study will identify factors predicting treatment success in patients with knee osteoarthritis.

## Abstract

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.

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.

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.