Activase (Alteplase) - Summary

ACTIVASE SUMMARY

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.

See all Activase indications & dosage >>

ACTIVASE NEWS HIGHLIGHTS

Published Studies Related to Activase (Alteplase)

Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. [2008.09.25]
BACKGROUND: Intravenous thrombolysis with alteplase [generic for Activase] is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke... CONCLUSIONS: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.) 2008 Massachusetts Medical Society

Comparison of alteplase and heparin in maintaining the patency of paediatric central venous haemodialysis lines: a randomised controlled trial. [2007.06]
OBJECTIVES: To determine whether the tissue plasminogen activator, alteplase [generic for Activase], is more effective than heparin in preventing blood clots developing in children's haemodialysis central lines between dialysis sessions... CONCLUSION: Alteplase is significantly more effective than heparin in preventing clot formation in central haemodialysis lines. This reduces morbidity and improves preservation of central venous access. It is more expensive, though relatively economic if packaged into syringes and stored frozen until needed, but reduces the costs of unblocking or replacing clotted lines.

Short and long alteplase dwells in dysfunctional hemodialysis catheters. [2005.04]
BACKGROUND: Hemodialysis catheter dysfunction (CD) is the inability to attain adequate blood pump speeds (BPS) and is attributed to thrombus or catheter malposition; alteplase [generic for Activase] (TPA) is often given in a variety of dwell times to treat CD. The purpose of this study was to determine if TPA dwell time affects short- or long-term catheter patency rates... CONCLUSION: This study demonstrates that although patency for the next HD run can be achieved with either short or long TPA dwell, neither is reliable in terms of long-term patency. Strategies that employ TPA for CD are temporary and allow a 2-week window during which more definitive therapies for HD access should be sought.

Comparison of rapidity of coronary recanalization in men with tenecteplase versus alteplase in acute myocardial infarction. [2004.06.15]
To determine whether tenecteplase (TNK-t-PA), a bioengineered variant of tissue-type plasminogen activator (t-PA) designed to accelerate thrombolysis, exhibits favorable properties compared with those of alteplase [generic for Activase], 266 men were studied </=6 hours after the onset of symptoms and signs of acute myocardial infarction... TNK-t-PA appears to induce recanalization more rapidly than alteplase, and thrombolysis initiated early after the onset of symptoms is associated with remarkably low mortality.

Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase: comparison with unfractionated heparin. [2003.10.15]
OBJECTIVES: We examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment-elevated acute myocardial infarction (AMl). BACKGROUND: Activated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro... CONCLUSIONS: Administration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients.

more studies >>

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 arm.

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.

Trial to Compare the Efficacy and Safety of a Single Bolus of TNK-tPA (Tenecteplase, Metalyse®) With Accelerated Infusion of rt-PA (Alteplase, Actilyse®) in Asian Patients With Acute Myocardial Infarction [Completed]
The objective of this trial was to compare the efficacy and safety of a single bolus of TNK-tPA (tenecteplase, Metalyse®) compared with rt-PA (alteplase, Actilyse®) in Asian patients.

A Study to Evaluate the Effects of YM872 on Brain Function and Disability When Administered in Combination With Alteplase (Tissue Plasminogen Activator) [Completed]
The purpose of this study is to determine if YM872 in combination with t-PA can reduce disability and brain damage from stroke. YM872 or placebo will be given as a continuous intravenous (iv) infusion for 24 hours. It is important that the study medication, YM872 or placebo, is administered prior to the completion of the t-PA administration. The clinical effects of YM872 in addition to t-PA will be determined by assessing neurological function and disability scores at follow up visits through Day 90 of the study.

Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR Stroke) Trial [Completed]
The purpose of this study is determine the effects of using of a combination of two drugs--integrilin (eptifibatide) and activase (recombinant tissue plasminogen activator, rt-PA, or recombinant t-PA)--to dissolve blood clots in patients who have a stroke.

more trials >>