Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial

Bennell KL, Paterson KL, Metcalf BR, et al. · JAMA

Null on both co-primary endpoints at 12 months: pain change -2.1 vs -1.8 points (difference -0.4, 95% CI -0.9 to 0.2; P=.17) and medial tibial cartilage volume change -1.4% vs -1.2% (difference -0.2%, 95% CI -1.9% to 1.5%; P=.81), the structural difference favouring placebo. Within-group pain improvement exceeded the 1.8-point minimum clinically important difference in both arms. Two of 31 secondary outcomes separated, both self-rated global improvement favouring PRP: overall improvement at 2 months, 48.2% vs 36.2% (risk ratio 1.37, 95% CI 1.05 to 1.80) and improvement in function at 12 months, 42.8% vs 32.1% (risk ratio 1.36, 95% CI 1.00 to 1.86). None of the 6 structural secondaries favoured PRP, and within one of them more PRP participants had three or more areas of cartilage thinning: 17.1% vs 6.8% (risk ratio 2.71, 95% CI 1.16 to 6.34; P=.02).

Population

Adults with symptomatic mild-to-moderate radiographic medial knee OA (mean age 61.9)

Intervention

3 weekly intra-articular injections of leukocyte-poor PRP

Comparator

Saline placebo injections

Limitations

The commercial leukocyte-poor kit is rated at a platelet concentration factor of 1.6 to 5 times whole blood with about 80% platelet recovery, and the trial assayed the preparation: growth factors and cytokines that promote healing were elevated and proinflammatory cytokines low. The authors' stated limits are that PRP preparations are not standardised so the result may not carry to others, that only Kellgren-Lawrence grade 2 or 3 knees were enrolled, and that participants were recruited from the community rather than from clinics. Blinding was measured and held: James Blinding Index 0.71 (95% CI 0.65 to 0.76) for participants and 0.74 (0.69 to 0.79) for injectors, with 269 of 288 (93%) completing. Adverse events were minor and transient, with more knee pain, swelling and stiffness after injection in the PRP arm. Funded by an NHMRC project grant, with the kits supplied free of charge by their manufacturer, Regen Lab SA.