Background: The burden of stroke is becoming an important issue in Asian countries, where half of the world's population lives. In Western populations, standard-dose intravenous tissue plasminogen activator (tPA) at a dose of 0.9 mg/kg administered up to 4.5 h following acute ischaemic stroke has been shown to improve clinical outcomes. However, the dosage of tPA in Asian populations varies, partly influenced by treatment costs in developing countries and the perceived racial differences in treatment response. Furthermore, no randomized controlled trial of intravenous tPA thrombolysis has been carried out in Asia with the exceptions of observational and multicentre registries in Japan. Summary of the Review: This review aims to examine the current use of low-dose tPA in Asian populations with particular emphasis on its clinical benefits. Historically, the findings of 2-chain tPA (duteplase) trials in the early 1990s were the basis of low-dose tPA in Japan, and standard-dose tPA was chosen taking into account a pilot dose escalation study. Most of the trials incorporating low-dose tPA suggested that low-dose tPA has clinical efficacy comparable with the standard dose and that it is associated with a lower incidence of symptomatic haemorrhage. It follows that consensus regarding the dosage of tPA is wanting. Conclusions: Standard-dose tPA would be a reasonable choice in Asian populations until the results are available from randomized controlled studies comparing low-dose with standard-dose tPA.

01 Sep 2012·Annals of the New York Academy of SciencesQ2 · CROSS-FIELD

Safety and efficacy of 0.6 mg/kg rt‐PA: optimum rt‐PA dose revisited

Q2 · CROSS-FIELD

Review

Author: Mori, Etsuro

Although the internationally recommended dosage of alteplase, a single‐chain rt‐PA, is 0.9 mg/kg, 0.6 mg/kg is the only approved dosage in Japan, and it is widely used there. Duteplase is a two‐chain rt‐PA, and based on findings of the duteplase trials in the early 1990s, the smaller dosage of 0.6 mg/kg of alteplase was tested in the Japan Alteplase Clinical Trial (J‐ACT), which indicated that the efficacy/safety profile of this dose was comparable to the 0.9 mg/kg dosage used in other countries. The Japan Alteplase Clinical Trial II (J‐ACT II) further demonstrated efficacy of 0.6 mg/kg alteplase with regard to vascular outcomes in patients with middle cerebral artery (MCA) occlusion. Finally, the Japan post‐Marketing Alteplase Registration Study (J‐MARS) confirmed the efficacy/safety profile of 0.6 mg/kg alteplase in a clinical setting that was comparable to the dose of 0.9 mg/kg in the European counterpart, the Safe Implementation of Thrombolysis in Stroke‐Monitoring Study (SITS‐MOST). The dose of 0.6 mg/kg seems to be optimal, at least in far‐east Asians, and might be extrapolated to other ethnic groups as well.

01 Sep 2009·Brain and nerve = Shinkei kenkyu no shinpo

[Prospects of thrombolytic therapy for acute ischemic stroke].

Review

Author: Minematsu, Kazuo ; Nakashima, Takahiro

The US Food and Drug Administration (FDA) approved the use of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in 1996, on the basis of the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study. IV rt-PA therapy at a dose of 0.9 mg/kg has been approved internationally for the treatment of hyperacute ischemic stroke. After a dose comparison study using duteplase and a multicenter study using a single dose of alteplase (Japan Alteplase Clinical Trial: J-ACT), the administration of IV rt-PA therapy at a dose of 0.6 mg/kg was approved in Japan in 2005. Immediately after the approval, the Japan Stroke Society published the Japanese guidelines for this low-dose therapy. Two years after the approval in Japan, the outcome of IV rt-PA therapy in Japan was observed to be comparable to that of NINDS rt-PA therapy and to those published in studies based in Western nations. Several trials have reported predictors of unfavorable outcome for IV rt-PA therapy. Patients with severe strokes (higher NIHSS score, coma), higher age at disease onset, aortic arch dissection, higher blood pressure, higher blood sugar, occlusion of the internal carotid artery (ICA) or tandem lesion of the left ICA and right middle cerebral artery (MCA), or the presence of major early ischemic changes as observed upon computed tomography (CT) or magnetic resonance imaging (MRI), showed a greater probability for unfavorable response to treatment. The results of the randomised 2008 trial conducted by the third European Cooperative Acute Stroke Study (ECASS III) suggested that treatment with IV rt-PA administered 3-4.5 hours after symptom onset can still induce significant improvement in clinical outcomes after an acute ischemic stroke as opposed to a placebo. MRI-based thrombolysis might be safer than standard CT-based thrombolysis. A combination of reperfusion therapies, IV rt-PA and sonothrombolysis, neuroprotective agents or antiplatelet agents may be effective. However, currently available data do not provide conclusive evidence for the safety or efficacy of these combination therapies. Patients having ICA occlusion may require alternatives including a higher dose of alteplase, combined IV/IA thrombolysis, or possibly mechanical thrombectomy by using a thrombus-removal device.

100 Deals associated with Duteplase

External Link

KEGG	Wiki	ATC	Drug Bank
D09823	Duteplase	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Myocardial Infarction	Preclinical	JP	Sumitomo Pharmaceuticals Co., Ltd.	-
Myocardial Infarction	Discovery	JP	Sumitomo Pharmaceuticals Co., Ltd.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis