Analysis of recruitment and outcomes in the phase I/IIa cethrin clinical trial for acute spinal cord injury

摘要

The Cethrin? clinical trial was an open-label Phase I/IIa trial undertaken to assess the safety, tolerability, and neurological status of patients with acute spinal cord injury (SCI) who were treated with escalating doses of Cethrin, a therapeutic protein drug that inactivates Rho. Recruitment, motor scores, and data on adverse events of treated patients have been reported (Fehlings et al.).24 While determining efficacy in a small open-label study is not possible, it is important to understand if the results warrant further clinical study, because clinical trial failures have wide ranging impacts. We have examined the clinical data to analyze time to recruitment and sensory outcomes, and compared the outcomes with available registry and placebo data. The average time to recruitment was 52 h, and there was a trend to improved sensory scores in treated patients with thoracic injury. An analysis of patients who recovered two motor levels or more suggests that there may be a larger responder population in the Cethrin-treated participants than in historical controls. We examined time to recruitment and found that the extent of motor and sensory recovery could not be explained by early surgery, and the Cethrin-treated patients showed favorable trends compared with the Surgical Timing in Acute SCI data. The trends reported here indicate that further study of Cethrin is warranted and provide useful guidance to establish effective clinical protocols.