Delving into the Latest Updates on Recombinant staphylokinase(Chengdu Diao Jiuhong Pharmaceutical Factory) with Synapse

Overview

Basic Info

Drug Type

Enzyme

Synonyms

Recombinant Staphylokinase(r-Sak), 重组葡激酶（地奥集团）, 依立通

Target

PLG

Mechanism

PLG stimulants(Plasminogen stimulants)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Myocardial Infarction

Inactive Indication-

Originator Organization

Chengdu Diao Jiuhong Pharmaceutical Factory

Active Organization

Chengdu Diao Jiuhong Pharmaceutical Factory

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (22 Nov 2006),

Myocardial Infarction

Regulation-

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Gene Sequence

Sequence Code 540044459

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

01 Feb 2024·Circulation. Cardiovascular interventions

Single Bolus r-SAK Before Primary PCI for ST-Segment–Elevation Myocardial Infarction

Article

Author: Wang, Jun ; Wang, Xiaoyan ; Zhang, Wenhao ; Chen, Xin ; Pu, Jun ; Xu, Yi ; Kong, Xiangqing ; Li, Chunjian ; Yang, Naiquan ; Liu, Kun ; Li, Baihong ; Ying, Lianghong ; Jiang, Meng ; Li, Chen ; Chen, Pengsheng ; Zhu, Xiaomei ; Zong, Jiaxin ; Yu, Hao ; Wang, Guoyu ; Wang, Tong ; Zhu, Li ; Huang, Jun ; Zhang, Fumin ; Jiang, Jun ; Chen, Zengguang ; Ma, Jiazheng ; Bai, Jianling ; Zhao, Xin ; Lu, Chuan ; Zhao, Bo ; Zhu, Jun ; Tan, Chunyue ; Eikelboom, John W. ; Gong, Xiaoxuan ; Dong, Zhou

BACKGROUND::

It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine whether in patients presenting with ST-segment–elevation myocardial infarction a single bolus recombinant staphylokinase (r-SAK) before timely PCI leads to improved patency of the infarct-related artery and reduces the infarct size.

METHODS::

This is an open-label, prospective, multicenter, randomized study. We enrolled patients aged 18 to 75 years who were within 12 hours of symptom onset of ST-segment–elevation myocardial infarction and expected to undergo PCI within 120 minutes. Patients were administered loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive 5 mg bolus of r-SAK or normal saline intravenously before PCI. The primary end point was Thrombolysis in Myocardial Infarction flow grade 2 to 3 or grade 3 in the infarct-related artery 60 minutes after thrombolysis. The infarct size was detected by cardiac magnetic resonance 5 days after randomization. The safety end point was major bleeding (Bleeding Academic Research Consortium ≥3) during 30-day follow-up.

RESULTS::

A total of 283 patients were screened from 8 centers and 200 were randomized (median age, 58.5 years; 14% female). The median symptom to thrombolysis time was 252.5 (interquartile range, 142.8–423.8) minutes and thrombolysis to coronary arteriography was 50.0 (interquartile range, 37.0–66.0) minutes. Patients randomized to r-SAK compared with normal saline more often had Thrombolysis in Myocardial Infarction flow grade 2 to 3 (69.0% versus 29.0%; P <0.001) and Thrombolysis in Myocardial Infarction flow grade 3 (51.0% versus 18.0%; P <0.001) and had smaller infarct size (21.91±10.84% versus 26.85±12.37%; P =0.016). There was no increase in major bleeding (r-SAK, 1.0% versus control, 3.0%; P =0.616).

CONCLUSIONS::

A single bolus r-SAK before primary PCI for ST-segment–elevation myocardial infarction improves infarct-related artery patency and reduces infarct size without increasing major bleeding.

REGISTRATION::

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05023681.

01 Nov 2023·American heart journal

Efficacy and safety of a bolus of half-dose r-SAK prior to primary PCI in ST-elevation myocardial infarction: Rationale and design of the OPTIMA-6 trial.

Article

Author: Huang, Jun ; Eikelboom, John W ; Zhao, Bo ; Jiang, Jun ; Yu, Hao ; Pu, Jun ; Li, Chen ; Zhao, Xin ; Bai, Jianling ; Gong, Xiaoxuan ; Zhu, Li ; Zhang, Fumin ; Tan, Chunyue ; Kong, Xiangqing ; Wang, Xiaoyan ; Zhu, Jun ; Li, Chunjian ; Zhang, Wenhao ; Chen, Xin ; Zhang, Xiwen ; Liu, Kun ; Zhong, Zihang ; Yang, Naiquan ; Wang, Qin

BACKGROUND:

Time to reperfusion is the key to the treatment of patients with ST-elevation myocardial infarction (STEMI). It is uncertain whether adjunctive thrombolytic therapy combined with contemporary antiplatelet agent ticagrelor improves outcomes as administered prior to primary percutaneous coronary intervention (PCI) expected to be performed within 120 minutes.

METHODS:

OPTIMA-6 is a multicenter, randomized, double-blind, placebo-controlled, and superiority trial to evaluate the efficacy of a bolus of half-dose recombinant staphylokinase (r-SAK) vs placebo prior to timely primary PCI in patients with STEMI. Enrollment began in April 2023 and is expected to enroll 2,260 patients at approximately 50 centers. Patients with acute STEMI presenting ≤12 hours of symptom onset and expected to undergo primary PCI within 120 minutes but more than 30 minutes are to be randomized to a bolus of half-dose r-SAK or placebo. All recruited patients will be mandatory to take aspirin and ticagrelor and receive a bolus of loading dose heparin before the thrombolytic therapy. The primary efficacy endpoint is major adverse cardiovascular events (MACE) within 90 days, and the MACE is defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, and major ventricular arrhythmia. The primary safety endpoints are major bleeding events (BARC 3, 5) within 90 days.

CONCLUSIONS:

OPTIMA-6 will reveal the efficacy and safety of a contemporary facilitated PCI with a bolus of half-dose r-SAK in combination with ticagrelor in patients with STEMI.

100 Deals associated with Recombinant staphylokinase(Chengdu Diao Jiuhong Pharmaceutical Factory)

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