摘要：

Background. There are still some unmet needs for stroke management and safety. DLBS1033 is a protein fraction extracted from the earthworm Lumbricus rubellus that has shown fibrinolytic and fibrinogenolytic activities, reduces blood viscosity, and inhibits platelet aggregation that it can be considered an add-on therapy and potential medical breakthrough in acute ischemic stroke management. Objective. This study is aimed at measuring the benefit of DLBS1033 in acute ischemic stroke management. Methods. This was a randomized, open-label trial at a referral stroke center from November 2019 to December 2020. Subjects who met the inclusion criteria were randomly divided into a control group and an experimental group. The control group received standard therapy consisting of aspirin 100 mg once daily, atorvastatin 20 mg once daily, and vitamin B12 100 mg three times daily. The experimental group received standard therapy and DLBS1033 three times daily. The functional outcomes were measured using the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) at baseline, hospital discharge, and day 30. Results. Collected data from 180 subjects was analyzed. The NIHSS scores' improvements were significantly greater in the experimental group compared to the control group at both hospital discharge ( vs. ; ) and day 30 ( vs. ; ). Compared with the control group, the improvements in the BI scores were significantly better in the experimental group, at both hospital discharge ( vs. ; ) and day 30 ( vs. ; ). The distribution of mRS scores was improved in both groups during 30 days of follow-up and was more favorable in the experimental group. In both groups, a favorable outcome () was achieved better at day 30 (86.7% vs. 80%; ) than at baseline (0% vs. 6.7%; ) and at hospital discharge (58.9% vs. 43.3%; ). There was no clinically significant adverse event related to the study product. Conclusions. DLBS1033 in addition to the standard care was more effective in improving functional status compared to standard care alone in acute ischemic stroke patients with a similar safety profile. 1. Introduction Stroke is a pathological manifestation of cerebral dysfunction that occurs for longer than 24 hours or induces mortality without indication of causes apart from vascular disorders [1]. Dependent on pathological background, stroke can be categorized into ischemic or hemorrhagic. Ischemic stroke is caused by a disruption of the blood supply to the brain that induces glucose and oxygen depletion in neurons, glia, and vascular cells [2]. Several treatments, including thrombolytic therapy, antiplatelet drugs, anticoagulants, and neuroprotective agents, are widely used to treat ischemic stroke [3]. There are still some unmet needs for stroke management and the safety of these interventions. Thrombolytic agents are not fibrin-specific, causing excessive bleeding [4, 5]. Antiplatelet drugs and anticoagulants prevent platelet aggregation and formation of fibrin strands; these agents can therefore be used to inhibit thrombogenesis but do not affect existing clots [6]. DLBS1033 is lumbrokinase obtained from the extraction of Lumbricus rubellus [7]. Lumbrokinase is a collective name for a group of bioactive proteolytic enzymes that has fibrinolytic and fibrinogenolytic activities, reduces blood viscosity, and reduces platelet aggregation [8, 9]. In addition, lumbrokinase is highly specific to fibrin, meaning lumbrokinase does not induce excessive bleeding [10]. This study is aimed at measuring the benefit of DLBS1033 in ischemic stroke patients as add-on therapy. Thus, if DLBS1033 shows a better outcome than standard therapy, DLBS1033 for ischemic stroke patients can be considered an add-on therapy. 2. Methods 2.1. Study Design and Subject Selection This study was conducted using a randomized, controlled, open-label design from November 2019 to December 2020. The subjects consisted of acute ischemic stroke patients at Bethesda Hospital Yogyakarta, Indonesia. The inclusion criteria in this study were as fol

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