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A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury.

ABSTRACT: Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI. The study enrolled patients 14-75 years of age with acute traumatic cervical SCIs, C4-C7 (motor level) on each side, and American Spinal Injury Association Impairment Scale (AIS) Grade A or B who had spinal decompression/stabilization surgery commencing within 72 h after injury. Patients were randomized 1:1 with stratification by age (<30 vs. ≥30 years) and AIS grade (A vs. B with sacral pinprick preservation vs. B without sacral pinprick preservation). A single dose of VX-210 or placebo in fibrin sealant was administered topically onto the dura over the site of injury during decompression/stabilization surgery. Patients were evaluated for medical, neurological, and functional changes, and serum was collected for pharmacokinetics and immunological analyses. Patients were followed up for up to 12 months after treatment. A planned interim efficacy-based futility analysis was conducted after ∼33% of patients were enrolled. The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI.

SUBMITTER: Fehlings MG

PROVIDER: S-EPMC8309435 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEarly routine intubation in motor-complete cervical spinal cord injury (CSCI) above the C5 level is a conventional protocol to prevent unexpected respiratory exacerbation (RE). However, in the context of recent advances in multidisciplinary respiratory management, the absolute indication for intubation in patients with CSCI based on initial neurologic assessment is controversial because of the drawbacks of intubation. This study aimed to redetermine the most important predictor of RE following CSCI after admission without routine intubation among patients admitted with motor-complete injury and/or injury above the C5 level to ensure timely intubation.MethodsWe performed a retrospective review of patients with acute traumatic CSCI admitted to our hospital without an initial routine intubation protocol from January 2013 to December 2017. CSCI patients who developed RE (defined as unexpected emergent intubation for respiratory resuscitation) were compared with those who did not. Baseline characteristics and severity of trauma data were collected. Univariate analyses were performed to compare treatment data and clinical outcomes between the two groups. Further, multivariate logistic regression was performed with clinically important independent variables: motor-complete injury, neurologic level above C5, atelectasis, and copious airway secretion (CAS).ResultsAmong 58 patients with CSCI, 35 (60.3%) required post-injury intubation and 1 (1.7%) died during hospitalization. Thirteen (22.4%) had RE 3.5 days (mean) post-injury; 3 (37.5%) of eight patients with motor-complete CSCI above C5 developed RE. Eleven of the 27 (40.7%) patients with motor-complete injury and five of the 22 (22.7%) patients with neurologic injury above C5 required emergency intubation at RE. Three of the eight CSCI patients with both risk factors (motor-complete injury above C5) resulted in emergent RE intubation (37.5%). CAS was an independent predictor for RE (odds ratio 7.19, 95% confidence interval 1.48-42.72, P = 0.0144) in multivariate analyses.ConclusionTimely intubation post-CSCI based on close attention to CAS during the acute 3-day phase may prevent RE and reduce unnecessary invasive airway control even without immediate routine intubation in motor-complete injury above C5.

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A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury.

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