Pro-UK (recombinant human pro-urokinase for injection) / Tasly - LARVOL DELTA

Mechanism and prospects of rhPro-UK in acute pulmonary embolism. (PubMed, Asian J Surg) - No abstract available

Journal • Cardiovascular • Pulmonary Embolism • Respiratory Diseases

FIBRINOLYSIS WAS REPLACED BEFORE IT WAS UNDERSTOOD. (PubMed, Cardiology) - "Methods This uses a sequential combination of a 5 mg mini bolus of tPA followed by an infusion of proUK (40 mg/hr) for 90 minutes...This requires doses of 90-100 mg of tPA over 60 minutes, which is neither very effective nor safe, due to a risk of bleeding complications from the lysis of hemostatic fibrin by tPA's fibrin affinity. Due to this problem, fibrinolysis was replaced by interventional procedures, like percutaneous coronary intervention (PCI), which is much slower, limited to clots larger than the catheter, but is generously reimbursed by third party payers."

Journal

rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2) (clinicaltrials.gov) - P3 | N=1552 | Completed | Sponsor: Tasly Biopharmaceuticals Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Mar 2024

Trial completion • Trial completion date • Cardiovascular • Ischemic stroke

ProUrokinase in Mild IsChemic strokE (PUMICE) (clinicaltrials.gov) - P3 | N=1446 | Completed | Sponsor: Beijing Tiantan Hospital | Recruiting ➔ Completed

Trial completion • Cardiovascular • Hematological Disorders • Ischemic stroke • Thrombosis

Evaluation of Recombinant Human Prourokinase in the Treatment of Acute Pulmonary Embolism (ERUPTE): A Randomized, Single-Blinded, Multicenter, Phase 2 Trial (ISTH 2024) - P2a | "Baseline characteristics were comparable among three groups (Table 1). All patients achieved a reduction in mean sPAP at 24 hours: rhPro-UK 40 mg group, -13.40 mmHg (95% confidence interval [CI], -24.10 to -2.71); rhPro-UK 50 mg, -15.42 mmHg (95% CI -25.93, -4.91); and alteplase, -16.02 mmHg (95% CI -25.53, -6.51) (Figure 1), but without inter-group differences (P > 0.05). Incidence of bleeding was lower in two rhPro-UK groups (63.9%, 23/37 at 40 mg; 55.6%, 20/35 at 50 mg) compared to alteplase group (82.9%, 29/35) (P=0.04)."

Clinical • Late-breaking abstract • P2 data • Cardiovascular • Pulmonary Embolism • Respiratory Diseases

RhPro-UK in acute ischemic stroke within 4.5 hours of stroke onset trial-2(The PROST-2 study): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial. (PubMed, Int J Stroke) - P3 | "URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591."

Head-to-Head • Journal • P3 data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke • Myocardial Infarction

rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2) (clinicaltrials.gov) - P3 | N=1552 | Active, not recruiting | Sponsor: Tasly Biopharmaceuticals Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2024 ➔ Dec 2024

Enrollment closed • Trial completion date • Cardiovascular • Ischemic stroke

Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction. (PubMed, J Cardiothorac Surg) - "Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI."

Journal • Cardiovascular • Hematological Disorders • Myocardial Infarction

In silico study of combination thrombolytic therapy with alteplase and mutant pro-urokinase for fibrinolysis in ischemic stroke. (PubMed, Comput Biol Med) - "The synergistic advantage of combining tissue plasminogen activator (tPA) with pro-urokinase (proUK) for thrombolysis has been demonstrated in several in vitro experiments, and a single site proUK mutant (m-proUK) has been developed for better stability in plasma. Therefore, future optimization of dose regimen should focus on limiting the tPA bolus while adjusting m-proUK dosage and infusion rate. Such adjustments could potentially maximize the therapeutic advantages of this combination therapy for ischemic stroke treatment."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Rationale and design of ProUrokinase in Mild IsChemic strokE (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. (PubMed, Stroke Vasc Neurol) - P3 | "This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset."

Journal • Cardiovascular • Cerebral Hemorrhage • Ischemic stroke

Thrombolysis with Recombinant Human Prourokinase 4.5-6 h After Acute Ischemic Stroke: A Phase IIa, Randomized, and Open-Label Multicenter Clinical Trial. (PubMed, CNS Drugs) - "In the 4.5-6 h time window, more than 60% of patients at either dose of rhPro-UK (50 mg or 35 mg) achieved functional independence at 90 days without increased mortality and sICH risk. Thus, intravenous rhPro-UK was effective and safe for patients with AIS within 4.5-6 h after stroke onset. While no significant differences were identified between different dosages of rhPro-UK regarding clinical outcomes, it is a logical step to further test the safety and efficacy of the low dose of rhPro-UK in a well-powered phase III study."

Journal • P2a data • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke

Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P3 | "The rhPro-UK group showed a similar rate of symptomatic ICH but fewer cases of systemic bleeding than the alteplase group. ClinicalTrials.gov Identifier: NCT03541668."

Clinical • Journal • P3 data • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke

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Dual Thrombolytic Therapy With Mutant Pro-Urokinase And Low Dose Alteplase For Ischemic Stroke (DUMAS) (ISC 2023) - P2 | "Background and AimsFibrinogen depletion is strongly associated with intracranial hemorrhage (ICH) and symptomatic ICH (sICH). ICH occurred in 16/121 (13%) patients in the intervention group and 16/117 (14%) patients in the control group (OR 0.99 [95% CI 0.46-2.14]). sICH occurred in 0/121 (0%) patients in the intervention group and in 3/117 (3%) patients in the control group (P=0.12).|ConclusionsDual thrombolytic treatment with m-proUK has an improved safety profile, as it does not cause fibrinogen depletion.|NCT04256473"

Late-breaking abstract • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology • Ischemic stroke

rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2) (clinicaltrials.gov) - P3 | N=1552 | Recruiting | Sponsor: Tasly Biopharmaceuticals Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2) (clinicaltrials.gov) - P3 | N=1552 | Not yet recruiting | Sponsor: Tasly Biopharmaceuticals Co., Ltd.

New P3 trial • Cardiovascular • Ischemic stroke