A Prospective Phase III Parallel, Randomised Controlled Trial Using Double-bolus Recombinant Staphylokinase (THR-100) vs Streptokinase in Patients With Acute Myocardial Infarction

This novel fibrinolytic agent is a 136 amino acid single chain protein secreted by some strains of Staphylococcus aureus and readily produced by recombinant DNA technology. Two natural variants of recombinant staphylokinase, THR-100 and SakSTAR, have been developed for investigational use in preliminary trials. Like SK, it forms an equimolar complex with plasmin which in turn activates plasminogen to plasmin. Unlike SK, the complexed, activated molecule (which undergoes proteolytic cleavage of the first ten amino acids to generate active staphylokinase) has a high degree of fibrin-selectivity in a human plasma milieu. This fibrin-selectivity is due in large measure to potent activation at the clot surface by trace amounts of plasmin, and rapid inactivation of the circulating complex by antiplasmin. Hence, it provides an interesting and promising alternative therapy.

开始日期2010-10-01

申办/合作机构

Bharat Biotech International Ltd.

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100 项与 Recombinant staphylokinase variant(Katholieke Universiteit Leuven) 相关的专利（医药）

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项与 Recombinant staphylokinase variant(Katholieke Universiteit Leuven) 相关的文献（医药）

2000-05-01·American Heart Journal2区 · 医学

Collaborative Angiographic Patency Trial Of Recombinant Staphylokinase (CAPTORS)

2区 · 医学

Article

作者: Teo, K. K. ; Burton, Jeffrey R. ; Armstrong, Paul W. ; Palisaitis, Donald ; Van de Werf, Frans ; Thompson, Christopher R. ; Rose, Barry ; Collen, Desire

BACKGROUNDWe undertook an angiographic, dose-finding study of staphylokinase (SAK42D variant) to evaluate its efficacy and safety in patients with acute ST-segment myocardial infarction.METHODS AND RESULTSPatients were studied within 6 hours of symptom onset and received SAK42D as a 30-minute infusion with 20% of the total dose given as a bolus. Eighty-two patients with a median age of 60 years (interquartile range 52 to 69 years), 84% male and 43% with an anterior myocardial infarction, were studied at a median time from symptom onset of 2.7 hours. There was a high degree of Thrombolysis in Myocardial Infarction (TIMI) 3 flow achieved with 15 mg of SAK42D, that is, 62%. Therefore after 21 patients had been studied at this dose the next dose of 30 mg was used and 65% TIMI 3 patency was achieved. At the peak dose of 45 mg, TIMI 3 90-minute patency was 63%. There were no allergic reactions, and no patient had intracranial hemorrhage. Four patients had major and 9 moderate bleeding during the study; 2 of the major and 5 of the moderate bleeding events occurred within 48 hours of commencement of treatment. The majority (62%) of these were related to vascular instrumentation, and there was no relation between the extent of bleeding and dose of SAK42D used. Forty-five minutes after cessation of SAK42D, there were small percent decrements in plasma fibrinogen and plasminogen levels that did not reach statistical significance. However, there were dose-related changes in alpha(2) anti-plasmin that revealed a borderline significant reduction that was dose related (P =.053).CONCLUSIONThese data revealed similar fibrinolytic efficacy across a 3-fold increment in dose, indicating that this study operated on a flat portion of the dose-response curve. The favorable efficacy/safety profile achieved with staphylokinase is encouraging, and further investigation is warranted.

1996-01-01·Thrombosis and Haemostasis2区 · 医学

Procoagulant Properties of Intravenous Staphylokinase Versus Tissue-Type Plasminogen Activator

2区 · 医学

Article

作者: Collen, D ; Vanderschuere, S ; Okada, K ; Moreau, H ; Lijnen, H R

SummaryThe fibrin-specificity and procoagulant effects of recombinant staphylokinase (Sak42D) were compared with those of recombinant tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction. Plasma samples were obtained at baseline and at 25 and 90 min, from 24 patients who were randomly assigned to a double bolus (15 mg each, 30 min apart) administration of Sak42D or to accelerated weight-adjusted rt-PA (maximum of 100 mg over 90 min). Baseline levels of fibrinopeptide A (FPA), prothrombin fragment 1+2 and thrombin-antithrombin III complex (TAT) were comparable in the Sak42D and rt-PA groups (p ≥ 0.6). In patients treated with Sak42D, plasma levels of FPA, prothrombin fragment 1+2 and TAT did not markedly increase during treatment (p = 0.06, p = 0.4 and p = 0.03, respectively). In contrast, during administration of rt-PA the levels of FPA, prothrombin fragment 1+2 and TAT increased significantly over baseline (p = 0.003, p < 0.0001 and p = 0.001, respectively). As a result, the levels of all three procoagulant parameters were significantly lower during treatment with Sak42D as compared to rt-PA. Thus, FPA levels in the Sak42D group (median values) were 40 ng/ml at 25 min and 11 ng/ml at 90 min, as compared to 88 ng/ml and 50 ng/ml in the rt-PA group (p = 0.0007 and p = 0.009, respectively). Prothrombin fragment 1+2 levels in the Sak42D group were 1.3 nM at 25 min and 1.2 nM at 20 min, as compared to 11 nM and 5.3 nM in the rt-PA group (both p < 0.0001). TAT levels were 4.7 ng/ml at 25 min and 6.2 ng/ml at 90 min in the Sak42D group, with corresponding values of 16 ng/ml and 9.6 ng/ml in the rt-PA group (p = 0.02 and p = 0.03, respectively).In the patients treated with Sak42D, no significant systemic fibrinolytic activation was observed, as revealed by unaltered levels of clotta-ble fibrinogen, plasminogen and a2-antiplasmin up to 90 min after the start of therapy. In contrast, the corresponding residual levels at 90 min in patients treated with rt-PA decreased to (mean ± SEM; n = 12) 62 ± 6%, 45 ± 5% and 52 ± 10%, respectively (all p < 0.01 versus the Sak42D group)These data confirm the high degree of fibrin-specificity of Sak42D and demonstrate that this is associated with significantly less generation of procoagulant activity in plasma after intravenous administration in patients with acute myocardial infarction

Animals2区 · 农林科学

Effects of Dietary Threonine Levels on Intestinal Immunity and Antioxidant Capacity Based on Cecal Metabolites and Transcription Sequencing of Broiler

2区 · 农林科学

ArticleOA

作者: Liu, Xing ; Ji, Shuyun ; Min, Yuna ; Ma, Shuxue ; Qi, Xi

This study aimed to determine the effects of different dietary threonine levels on the antioxidant and immune capacity and the immunity of broilers. A total of 432 one-day-old Arbor Acres (AA) broilers were randomly assigned to 4 groups, each with 6 replicates of 18 broilers. The amount of dietary threonine in the four treatments reached 85%, 100%, 125%, and 150% of the NRC (Nutrient Requirements of Poultry, 1994) recommendation for broilers (marked as THR85, THR100, THR125, and THR150). After 42 days of feeding, the cecum contents and jejunum mucosa were collected for metabolic analysis and transcriptional sequencing. The results indicated that under the condition of regular and non-disease growth of broilers, compared with that of the THR85 and THR150 groups, the metabolic profile of the THR125 group was significantly higher than that of the standard requirement group. Compared with the THR100 group, the THR125 group improved antioxidant ability and immunity of broilers and enhanced the ability of resisting viruses. The antioxidant gene CAT was upregulated. PLCD1, which is involved in immune signal transduction and plays a role in cancer suppression, was also upregulated. Carcinogenic or indirect genes PKM2, ACY1, HK2, and TBXA2 were down-regulated. The genes GPT2, glude2, and G6PC, which played an important role in maintaining homeostasis, were up-regulated. Therefore, the present study suggests that 125% of the NRC recommendations for Thr level had better effects on antioxidant and immune capacity, as well as maintaining the homeostasis of the body.

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