ABSTRACT
Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.
ABSTRACT
OBJECTIVES: We aimed to assess the feasibility of using a telemedicine bridge clinic model as a low-barrier mechanism to initiate patients on medication treatment for opioid use disorder (MOUD) while facilitating engagement in long-term treatment. METHODS: We established a telemedicine bridge clinic after the U.S. Drug Enforcement Administration temporarily suspended regulations limiting initial treatment of patients with buprenorphine via both audiovisual and audio-only technology during the COVID-19 public health emergency. The rate of engagement in medication treatment for opioid use disorder MOUD based upon review of the Prescription Drug Monitoring Program is described. Referral sources, technology utilization, and payer mix are also presented. RESULTS: The Bridge Clinic scheduled 208 new patient visits and physicians evaluated 200, a show rate of 96% from April 2020 to July 2021. Of the 200 patients who were treated, 192 (96%) were diagnosed with opioid use disorder. Most patients (159/200, 79%) scheduled audio-only visits. At least 1 prescription for buprenorphine was filled by 185/192 (96%) of opioid use disorder patients within 30 days of the telemedicine visit and 147/192 (77%) of patients filled 2 or more prescriptions. Most patients were covered by Medicaid (62%) or were uninsured (19%). There was no significant difference in outcomes for patients evaluated by audio-only vs. audiovisual techniques. CONCLUSION: A Bridge Clinic using audiovisual and audio-only telemedicine served a high-risk, vulnerable population and facilitated engagement in evidence-based MOUD.