Otaplimastat is a neuroprotectant that inhibits matrix metalloproteases pathway, and reduces edema and intracerebral hemorrhage (ICH) 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.
This was a phase 2, two‐part, multicenter trial in stroke patients (19–80 years) receiving rtPA. Intravenous otaplimastat was administered <30 min 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, 80 mg or a placebo. The primary endpoint was the occurrence of parenchymal hematoma (PH) on day 1. Secondary endpoints included serious adverse events (SAE), mortality, and modified Rankin scale (mRS) distribution at 90 days (clinicaltrials.gov Identifier: NCT02787278).
No safety issues were encountered in stage 1. The incidence of PH during stage 2 was comparable: 0/22 with the placebo, 0/22 with otaplimastat 40 mg, and 1/21 with the 80 mg dose. No differences in the SAE (13%, 17%, 14%) or death (8.3%, 4.2%, 4.8%) were observed among the three groups. Three adverse events (chills, muscle rigidity, hepatotoxicity) were judged to be related to otaplimastat.
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.