Intradiscal Nucleus Pulposus Allograft Versus Sham Procedure in Patients with Lumbar Discogenic Pain: A Randomized Clinical Trial

Background/Objectives: Chronic lumbar discogenic pain is a leading cause of disability. We evaluated the efficacy and safety of a single intradiscal injection of nucleus pulposus allograft compared with a sham procedure. Methods: Randomized, double-blind, sham-controlled superiority trial at five Australian pain centers. Adults with chronic lumbar discogenic pain were assigned 1:1 to allograft or sham. The prespecified primary endpoint was the proportion of participants with a ≥30% reduction in back pain visual analog scale (VAS) at 6 months. Sham non-responders could cross over to allograft treatment at 3 months; their 3-month values were carried forward to 6 months (last observation carried forward, LOCF). Results: A total of 121 participants were randomized (allograft 60, sham 61). At 3 months, the last visit at which both groups were fully observed, 53% (32/60) of allograft and 5% (3/60) of sham participants achieved the back pain responder threshold (difference 48 percentage points, 95% CI 33 to 61; p < 0.001). At 6 months, with LOCF for the 55 of 61 sham participants who crossed over, responder rates were 60% (36/60) versus 1.6% (1/61) (difference 58 percentage points, 95% CI 44 to 70; p < 0.001); superiority persisted in sensitivity analyses unless ≥45% of crossover participants would have responded untreated. Oswestry Disability Index responder rates were 53% versus 32% at 3 months and 60% versus 31% at 6 months (LOCF). Within 3 months, procedure- or product-related adverse events occurred in 6/60 (10%) allograft and 3/61 (5%) sham participants; two of these events were serious. Conclusions: Nucleus pulposus allograft produced large, clinically meaningful reductions in discogenic back pain compared with sham in the fully observed 3-month comparison. Most sham participants crossed over at three months as permitted by the protocol, and their three-month values were carried forward to the 6-month primary endpoint analysis. Registration: NCT06615505.