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FDA Approves Cathflo Activase (Alteplase) To Clear Blocked Central Venous Access Devices

SAN FRANCISCO, CA -- September 5, 2001 -- Genentech, Inc. announced today that its thrombolytic agent Cathflo ActivaseŽ (Alteplase), a tissue plasminogen activator, has been approved by the U.S. Food and Drug Administration (FDA) for the restoration of function to central venous access devices (CVADs), as assessed by the ability to withdraw blood.

Cathflo Activase, available in a 2 mg single-patient-use vial, is the only marketed thrombolytic available for this indication and offers medical professionals a viable treatment option for a CVAD complication that can hinder patient care.

"The availability of Cathflo Activase may help patients avoid surgical removal and replacement of blocked CVADs," said COOL-2 (Cardiovascular thrombolytic to Open Occluded Lines - 2) pivotal trial lead investigator Steven R. Deitcher, MD, director of clinical thrombosis and vascular research in the Department of Cardiovascular Medicine, section of vascular medicine and staff physician in the Department of Hematology and Medical Oncology at The Cleveland Clinic in Ohio. "Most importantly, an open CVAD line allows for the uninterrupted administration of critical medical therapies essential to many life-saving treatment regimens."

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 or withdraw blood.

An estimated five million CVADs are placed each year in the U.S. to provide patients with life-saving medications and critical treatment. Occlusions or blockages due to formation of a blood clot (thrombus) within or at the tip of the CVAD catheter are a common problem that can block the administration of these therapies to patients. It is estimated that up to 25 percent of CVADs become occluded and that 60 percent of those occlusions are caused by the formation of a blood clot.

Cathflo Activase works by activating plasminogen, which dissolves fibrin (a substance that causes blood to clot), breaking down the thrombus and restoring function to the CVAD.

FDA approval of Cathflo Activase is based on two Phase III clinical trials designed to assess its safety and efficacy in restoring function to CVADs that had become occluded due to a blood clot: the COOL efficacy trial and the COOL-2 safety trial. Neither study included patients with hemodialysis catheters, known mechanical occlusions, or those at high risk for bleeding or embolization.

The COOL efficacy trial, a Phase III, six-month, randomized, placebo-controlled, double-blind study, enrolled 150 adult and pediatric patients (ages two-16) with CVAD occlusion up to 24 hours. In this study, Cathflo Activase or placebo was instilled directly into the lumen opening (tube of the catheter that carries fluid through a CVAD directly to the vein), 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 second dose of Cathflo Activase as either a first active dose (for placebo group) or follow-up dose (treatment group).

The study found that patients treated with up to two active doses had restored CVAD function. After the initial dose of Cathflo Activase, 67 percent (n=51) of the patients' CVADs were functional, compared to 16 percent (n=12) restored in the placebo group. A total of 88 percent (n=112) of Cathflo Activase patients treated with either a double-dose or single-dose had restored CVAD function. These data have been published in the August issue of the Journal of Vascular and Interventional Radiology (JVIR).

The COOL-2 trial, a Phase IIIb, single-arm, open-label study, enrolled 995 adult and pediatric patients (ages two-16) with CVAD occlusion present for any duration to determine the safety of Cathflo Activase for restoring function to occluded CVADs.

The study demonstrated that the treatment has an acceptable safety profile in CVAD clearance and reconfirmed the product's efficacy, restoring CVAD function to 85 percent (n=844) of patients after up to two doses.

In the two trials, only serious adverse events thought to be possibly related to the study drug were reported. The most serious adverse events reported were sepsis, gastrointestinal bleeding and venous thrombosis.

Cathflo Activase will be marketed using a different dose and dosing regimen from Activase. Following Abbott Laboratories' removal of urokinase from the CVAD clearance market in late 1998, Genentech began working with the FDA to bring Activase to the market for use in occluded CVADs.

SOURCE: Genentech Corporation

Related Links: Activase (Alteplase) and Genentech Corporation.

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