Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study
- Authors
- Kim, Jong S.; Lee, Kyung Bok; Park, Jong-Ho; Sung, Sang Min; Oh, Kyungmi; Kim, Eung-Gyu; Chang, Dae-il; Hwang, Yang Ha; Lee, Eun-Jae; Kim, Won-Ki; Ju, Chung; Kim, Byung Su; Ryu, Jei-Man
- Issue Date
- Feb-2020
- Publisher
- John Wiley & Sons Inc.
- Keywords
- Stroke; Neurology
- Citation
- Annals of Neurology, v.87, no.2, pp 233 - 245
- Pages
- 13
- Journal Title
- Annals of Neurology
- Volume
- 87
- Number
- 2
- Start Page
- 233
- End Page
- 245
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/3157
- DOI
- 10.1002/ana.25644
- ISSN
- 0364-5134
1531-8249
- Abstract
- Objective Otaplimastat is a neuroprotectant that inhibits matrix metalloprotease pathway, and reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA) in animal stroke models. We aimed to assess the safety and efficacy of otaplimastat in patients receiving rtPA. Methods This was a phase 2, 2-part, multicenter trial in stroke patients (19-80 years old) receiving rtPA. Intravenous otaplimastat was administered <30 minutes after rtPA. Stage 1 was a single-arm, open-label safety study in 11 patients. Otaplimastat 80 mg was administered twice daily for 3 days. Stage 2 was a randomized, double-blind, placebo-controlled study involving 69 patients, assigned (1:1:1) to otaplimastat 40 mg, otaplimastat 80 mg, or a placebo. The primary endpoint was the occurrence of parenchymal hematoma (PH) on day 1. Secondary endpoints included serious adverse events (SAEs), mortality, and modified Rankin scale (mRS) distribution at 90 days ( identifier: NCT02787278). Results No safety issues were encountered in stage 1. The incidence of PH during stage 2 was comparable: 0 of 22 with the placebo, 0 of 22 with otaplimastat 40 mg, and 1 of 21 with the 80 mg dose. No differences in SAEs (13%, 17%, 14%) or death (8.3%, 4.2%, 4.8%) were observed among the 3 groups. Three adverse events (chills, muscle rigidity, hepatotoxicity) were judged to be related to otaplimastat. Interpretation Intravenous otaplimastat adjunctive therapy in patients receiving rtPA is feasible and generally safe. The functional efficacy of otaplimastat needs to be investigated with further large trials. ANN NEUROL 2019
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Collections - College of Medicine > Department of Neurology > 1. Journal Articles
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