Activase (Alteplase) is a tissue plasminogen activator produced by recombinant DNA technology. It is a sterile, purified glycoprotein of 527 amino acids. It is synthesized using the complementary DNA (cDNA) for natural human tissue-type plasminogen activator obtained from a human melanoma cell line. The manufacturing process involves the secretion of the enzyme alteplase into the culture medium by an established mammalian cell line (Chinese Hamster Ovary cells) into which the cDNA for alteplase has been genetically inserted. Fermentation is carried out in a nutrient medium containing the antibiotic gentamicin, 100 mg/L. However, the presence of the antibiotic is not detectable in the final product.
Activase® (Alteplase) is indicated for use in the management of acute myocardial infarction in adults for the improvement of ventricular function following AMI, the reduction of the incidence of congestive heart failure, and the reduction of mortality associated with AMI. Treatment should be initiated as soon as possible after the onset of AMI symptoms (see CLINICAL PHARMACOLOGY).
Activase® (Alteplase) is indicated for the management of acute ischemic stroke in adults for improving neurological recovery and reducing the incidence of disability. Treatment should only be initiated within 3 hours after the onset of stroke symptoms, and after exclusion of intracranial hemorrhage by a cranial computerized tomography (CT) scan or other diagnostic imaging method sensitive for the presence of hemorrhage (CONTRAINDICATIONS).
Activase® (Alteplase) is indicated in the management of acute massive pulmonary embolism (PE) in adults:
For the lysis of acute pulmonary emboli, defined as obstruction of blood flow to a lobe or multiple segments of the lungs.
For the lysis of pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.
The diagnosis should be confirmed by objective means, such as pulmonary angiography or noninvasive procedures such as lung scanning.
Published Studies Related to Activase (Alteplase)
Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design. [2011.08]
BACKGROUND: TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. PURPOSE: (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs... CONCLUSIONS: (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.
SYNTHESIS expansion: design of a nonprofit, pragmatic, randomized, controlled trial on the best fast-track endovascular treatment vs. standard intravenous alteplase for acute ischemic stroke. [2011.06]
Rationale Reperfusion in ischemic stroke can be pursued by either systemic intravenous thrombolysis or endovascular treatment. However, systemic intravenous thrombolysis with alteplase within 4.5 h of symptom onset in selected patients is the only medication of proven efficacy... Secondary: neurological deficit seven-days after thrombolysis and the safety of the procedure on the basis of events reported within seven-days following thrombolysis - symptomatic cerebral hemorrhage, fatal and nonfatal stroke, death from any cause, neurological deterioration.
Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in
acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design. 
facilitate future approval of similar designs... CONCLUSIONS: (1) The design was innovative and efficient. Per protocol, type I
Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR. [2010.09]
BACKGROUND: In September, 2008, the European Acute Stroke Study III (ECASS III) randomised trial and the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) observational study reported the efficacy and safety of the extension of the time window for intravenous alteplase treatment from within 3 h to within 4.5 h after stroke onset. We aimed to assess the implementation of the wider time window, its effect on the admission-to-treatment time, and safety and functional outcome in patients recorded in SITS-ISTR... INTERPRETATION: Since October, 2008, thrombolysis within 3-4.5 h after stroke has been implemented rapidly, with a simultaneous increase in the number of patients treated within 3 h; admission-to-treatment time has not increased. Safety and functional outcomes are less favourable after 3 h, but the wider time window now offers an opportunity for treatment of those patients who cannot be treated earlier. Thrombolysis should be initiated within 4.5 h after onset of ischaemic stroke, although every effort should be made to treat patients as early as possible after symptom onset. FUNDING: Boehringer Ingelheim, Ferrer, the European Union Public Health Executive Authority, and Medical Training and Research (ALF) from Stockholm County Council and Karolinska Institutet. Copyright 2010 Elsevier Ltd. All rights reserved.
Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial. [2009.12]
BACKGROUND: In the European Cooperative Acute Stroke Study III (ECASS III), alteplase administered 3.0-4.5 h after the onset of stroke symptoms resulted in a significant benefit in the primary endpoint (modified Rankin scale [mRS] score 0-1) versus placebo, with no difference in mortality between the treatment groups. Compared with the 0-3 h window, there was no excess risk of symptomatic intracranial haemorrhage. We assessed the usefulness of additional endpoints and did subgroup and sensitivity analyses to further investigate the benefit of alteplase... INTERPRETATION: Our results support the use of alteplase up to 4.5 h after the onset of stroke symptoms across a broad range of subgroups of patients who meet the requirements of the European product label but miss the approved treatment window of 0-3 h. FUNDING: Boehringer Ingelheim.
Clinical Trials Related to Activase (Alteplase)
IV vs. IA tPA (Activase) in Acute Ischemic Stroke With CTA Evidence of Major Vessel Occlusion [Active, not recruiting]
Stroke is the third leading cause of death in the United States, responsible for 158,488
deaths in 1998 (American Heart Association). Nationwide, each year, an estimated 600,000 to
750,000 people suffer a new or recurrent stroke. Cerebral infarction comprises 80% of all
strokes and is the result of a complex series of cellular metabolic events that occur rapidly
after interruption of blood flow to a region of the brain. The extent of the brain damage is
dependent on the duration and severity of the cerebral ischemia. Acute thrombus formation or
migration is the principal cause of blood flow interruption in at least 75% of cerebral
infarctions. In several animal models of focal cerebral ischemia, restoration of cerebral
blood flow within two to six hours after initial occlusion has been associated with smaller
volumes of cerebral infarction and improved functional outcome. An effective way of
dissolving the thrombus is by administration of recombinant tissue plasminogen activator or
Activase (Alteplase, rt-PA), which promotes the proteolytic action of plasmin from
plasminogen at the site of a clot. In this study, the drug, Activase, will be administered in
subjects with acute ischemic stroke (AIS) intravenously (IV) or by local intra-arterial (IA)
injection. The use of the intravenous administration within 3 hours of stroke symptom onset
is FDA approved whereas the intra-arterial administration, despite evidence of potential
benefit, is not currently FDA approved. Although not FDA approved, this study will evaluate
the effectiveness of IA thrombolysis with Activase, used in AIS because of its higher rate of
recanalization , potential expansion of the time window out to 6 hours, and lower doses of
thrombolytic agent used compared with systemic or intravenous Activase. The study is designed
to test the feasibility and provide preliminary safety data regarding the relative benefits
and risks of IA Activase as compared to IV Activase when administered per the NINDS rt-PA
stroke study protocol, i. e. randomized within 3 hours of onset of symptoms of ischemic stroke
then treated within 3 hours in the IV Activase arm and within 4 hours in the IA Activase
Cathflo Activase Pediatric Study [Completed]
This was a Phase IV, open-label, single-arm, multicenter trial that was to be conducted at
~60 sites in the United States. Approximately 300 pediatric subjects with dysfunctional
CVADs (including catheters with valves, multiple lumens, umbilical catheters, and implanted
ports) were to be treated with up to two serially instilled doses of Cathflo Activase.
Interventional Management of Stroke (IMS) III Trial [Recruiting]
The purpose of this study is to compare two different treatment approaches—combined
intravenous and intra-arterial treatment including recombinant tissue plasminogen activator
(rt-PA) and standard intravenous (IV) rt-PAâto restoring blood flow to the brain.
EffIcicy and Safety of Activase vs Placebo in CPE/Empyemas [Recruiting]
Prolonged Hemodialysis Catheter Survival With Copolymer Coating and Rt-PA [Recruiting]
Surface thrombogenicity of standard double lumen catheters (stDLC) and surface modified
film-coated domain structured double lumen catheters (fcDLC) consisting of a novel reactive
polyurethane copolymer coating showed that in vitro measured surface thrombogenicity was
reduced in the modified catheter compared with standard catheter. The clinical investigation
revealed that both number of days before catheter removal according to clinical requirements
and number of treatments per catheter were significantly higher with the modified catheter
as compared with the standard catheter.
Recombinant tissue plasminogen activator (rt-PA) has been used primarily to treat catheter
thrombosis. The relatively high cost of rt-PA and its theoretical potential to cause
bleeding, as well as the morbidity and mortality associated with catheter malfunction and
infection, justify the need for more definitive evidence of the efficacy of rt-PA as a
No study aims to evaluate the impact of rt-PA locking in long-term Hemodialysis (HD)
uncuffed catheters survival.
Reports of Suspected Activase (Alteplase) Side Effects
Chest Pain (32),
Cerebral Haemorrhage (28),
Brain Oedema (14),
Ventricular Tachycardia (11),
Haemorrhage Intracranial (10), more >>
Page last updated: 2013-02-10