Cathflo® Activase® (Alteplase)
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 in adult and pediatric patients (2001 and 2005, respectively) for the restoration of function to central venous access devices that have become occluded due to a blood clot. 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.
Important Safety Information In clinical trials, the most serious adverse events reported after treatment were serious blood infections, consider stomach and intestinal bleeding, and clots that form within veins. Cathflo Activase® (Alteplase) should be used with caution if the catheter is infected or might be infected. Using Cathflo Activase in patients with infected catheters may release an infection within the catheter into their bloodstream.
In the first two studies (which enrolled primarily adult patients) involving over 1100 patients, four catheter-related infections occurred from 15 minutes to 1 day after treatment with Alteplase, and a fifth infection occurred on Day 3 after Alteplase treatment. All five patients tested positive for infection in their catheter or infection in their blood within 24 hours after they had symptoms.
Three patients had major bleeding from a source in the digestive system 2 to 3 days after Alteplase treatment. One case of bleeding at the injection site was observed 4 hours after treatment in a patient that already had a low platelet count (platelets help a person's blood to clot). There were no reports of bleeding in the brain.
There were three cases of blood clots happening in the artery below the collar bone, and in arteries in the arm; and these were reported 3 to 7 days after treatment. There were no reports of clots in the lungs.
In the pediatric trial of 300 patients under age 17, three cases of serious blood infection occurred 2 to 44 hours after treatment with Cathflo Activase. All of these patients had evidence of infection before treatment with Cathflo Activase.
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.