Cathflo® Activase® (Alteplase)

Full Prescribing Information

Restoring Function to Central Venous Access Devices as Assessed by the Ability to Withdraw Blood Cathflo Activase is a recombinant form of a naturally-occurring enzyme produced by the body known as tissue plasminogen activator, or t-PA. Cathflo Activase was approved by the FDA in September 2001, and later approved in pediatric patients in January 2005. There are currently no other pharmaceutical agents marketed for this indication.

Central venous access device, or CVAD, is a broad term that includes many types of catheters (thin, flexible hollow tubes) that are inserted into and positioned within a vein in the body to deliver therapies to the bloodstream or withdraw blood for testing. It is estimated that 5 million CVADs are placed each year in the U.S., and occlusions are a common complication. It is estimated that up to 25 percent of all CVADs become occluded and that 60 percent of those occlusions are caused by thrombosis, the formation of a blood clot.

Cathflo Activase is a thrombolytic that works by targeting fibrin (the substance that causes blood to clot), dissolving the thrombus (blood clot) and restoring function to the CVAD.

Cathflo Activase is currently marketed in a different dosing regimen under the trade name Activase® (Alteplase, recombinant) for the treatment of acute myocardial infarction (AMI), acute ischemic stroke within three hours of symptom onset, and acute massive pulmonary embolism. Activase was first licensed for marketing by the FDA for the treatment of AMI in November 1987.

Clinical Trials

• Genentech, Inc., studied Cathflo Activase in two Phase III clinical trials assessing the safety and efficacy of the product for use in clearing occluded CVADs. The trials in the COOL (Cardiovascular thrombolytic to Open Occluded Lines) program included the COOL efficacy trial and the COOL-2 safety trial.
• Cathflo Activase was instilled as a 2 mg bolus injection directly into the lumen opening (tube that carries fluid through a CVAD catheter directly to the vein) of a CVAD. If function was not restored after the first administration, a second 2 mg dose was given after 30-minute or 120-minute dwell times.

Efficacy

• The COOL efficacy trial, a Phase III, six-month, randomized, placebo-controlled, double-blind study, enrolled 150 patients with CVAD occlusion up to 24 hours in duration. In this study, Cathflo Activase or placebo was instilled directly into the lumen opening, for a dwell time of 120 minutes. Patients with CVADs that remained occluded after an initial dose of Cathflo Activase or placebo were administered a 2mg dose of Cathflo Activase as either a first dose (for the placebo group) or follow-up dose (treatment group).
• Study results demonstrated that after just one dose of Cathflo Activase, 67 percent of the patients' CVADs were functional, compared to 16 percent restored in the placebo group. A total of 88 percent of Cathflo Activase patients treated with either a double-dose or single-dose had restored CVAD function. COOL efficacy data was presented at the International Symposium on Endovascular Therapy in Miami Beach, Florida, January 2001 and published in the August issue of the Journal of Vascular and Interventional Radiology.
• In January 2005, Genentech announced results from the Cathflo Activase Pediatric Study (CAPS), demonstrating that Cathflo Activase can be used to restore function to central venous catheters in pediatric patients. The label extension was supported by findings from the CAPS study, a Phase IIIb open-labeled, single-arm trial involving 310 patients between the ages of 2 weeks and 17 years.

Safety

• In clinical trials, the most serious adverse events reported after treatment were sepsis, gastrointestinal bleeding, and venous thrombosis. Cathflo Activase should be used with caution in the presence of known or suspected infections in the catheter.

Past and Current Treatment Options

• The thrombolytic urokinase was previously used for CVAD clearance until the FDA recommended its removal from the marketplace in December 1998 due to inconsistencies in the manufacturing process at Abbott Laboratories.
• Current treatments include invasive techniques such as surgically removing and replacing the CVAD, which can be an uncomfortable, expensive and potentially risky procedure for patients. But it can be even more dangerous and uncomfortable for patients if CVADs remain occluded, which can prevent proper administration of needed fluids and medications or require that patients undergo multiple needle sticks to withdraw blood samples.
• Approved by the U.S. Food and Drug Administration in September 2001, Cathflo Activase restores function of the CVAD without the need for invasive surgery. A convenient 2 mg single-patient-use vial will enable simple dosing and administration.