Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial)

Abstract

Background Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the ‘active’ ingredients are unknown. Designing and executing an adequate and ‘blindable placebo’ version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used ‘state-of-art’ exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA. Methods In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients’ global assessment of disease impact, physical performance tests, and presence of knee joint swelling. Discussion This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA. Trial registration www.ClinicalTrials.govNCT03843931. Prospectively registered on 18 February 2019.

Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial

“…Potential participants were informed about the trial by an investigator who obtained written informed consent and coordinated trial inclusion. Information was delivered neutrally, ensuring that descriptions of both interventions were promoted equally including that the investigators had no treatment preference (clinical equipoise) 11. Saline injections were described as inert, yet with potential beneficial effects that may compare to those of exercise and education.…”

“…Saline injections were described as inert, yet with potential beneficial effects that may compare to those of exercise and education. The participants were informed that ‘active ingredients’ in both interventions are unverified and involves the sum and interaction of many factors 11. The most symptomatic knee at baseline was chosen as the study knee.…”

“…Intra-articular saline injection is one such inert treatment and is commonly used as a comparator in clinical trials for knee OA. In indirect comparisons, the symptom response to saline injection was comparable to that of exercise in knee OA 9–11…”

Short- and Midterm Comparison of Platelet-Rich Plasma with Hyaluronic Acid versus Leucocyte and Platelet-Rich Plasma on Pain and Function to Treat Hip Osteoarthritis. A Retrospective Study

“…The evidence that PRP, CS, and HA has a placebo effect should not be considered conclusive, as it must be considered that the equivalence of saline solution and these therapies has been studied in only 11 studies, taking into consideration 6 months of follow-up. Furthermore, there is no agreement on whether it can be accurate to consider intra-articular saline solution as a placebo: it determines a substantial pain reduction, especially in a short time span, as shown by several studies primarily on patients with knee osteoarthritis [16,17].…”

“…Gels 2021, 7, x FOR PEER REVIEW 5 of 11 whether it can be accurate to consider intra-articular saline solution as a placebo: it determines a substantial pain reduction, especially in a short time span, as shown by several studies primarily on patients with knee osteoarthritis [16,17]. Further evidence supporting the short-term efficacy of biological gel injections as a strong analgesic solution for HOA comes from a previous paper by Sante and colleagues: in a comparative study, either PRP or HA intra-articular injections were administered to a total of 43 patients suffering from severe monolateral HOA.…”