Cathflo® Activase® Frequently Asked Questions

General Information

Cathflo is a thrombolytic agent that gives you a viable treatment option for central venous access device (CVAD) occlusions as assessed by the ability to draw blood. It is a human tissue plasminogen activator (alteplase) produced by recombinant DNA technology. In the clinical trials, the most serious adverse events reported after treatment were sepsis, gastrointestinal bleeding, and venous thrombosis.8

Cathflo is the only FDA-approved thrombolytic agent for restoration of function to CVADs as assessed by the ability to withdraw blood.8

Cathflo binds to fibrin in the thrombus, converting entrapped plasminogen to plasmin, initiating local fibrinolysis.8

As with native tissue-plasminogen activator, Cathflo is highly fibrin-specific. It therefore acts specifically on fibrin-rich clots in the occluded catheter. The clinical significance of fibrin specificity is unknown.8

Cathflo has proven efficacy.8 In COOL-1, Cathflo restored function to 88% (112/127) of central lines after up to 2 doses using a 120-minute dwell time for each in catheters with occlusions present for up to 24 hours.8 In COOL-1 and COOL-2, Cathflo restored function to 68% (796/1043) of central lines after 1 dose and 88% (902/1043) of central lines after 2 doses in catheters with occlusions present for less than 14 days.8

COOL-1 was a double-blind, randomized, placebo-controlled study of 150 patients to evaluate the efficacy of Cathflo 2 mg/2 mL, in up to 2 doses, with function assessed at 120 minutes.8 COOL-2 was a phase III, single-arm, open-label, multicenter study of 995 patients to evaluate the safety of serial administration of up to 2 doses of Cathflo. Secondary objectives included assessing success rates at 30 minutes and 120 minutes.8

The most frequent adverse reaction associated with all thrombolytics in all approved indications is bleeding.8

Adverse events seen in the largest clinical trial involving Cathflo included sepsis (0.4%), a major hemorrhage (0.4%), gastrointestinal bleeding (0.3%), and venous thrombosis (0.3%).10 There were no instances of intracranial hemorrhage (ICH) or embolic events.8

Cathflo should not be administered to patients with known hypersensitivity to alteplase or any component of the formulation. It should be used with caution in the presence of known or suspected infections in the catheter. Using Cathflo in patients with infected catheters may release a localized infection into the systemic circulation.8

The Cathflo Activase Pediatric Study (CAPS) was designed to evaluate the safety profile in 310 pediatric patients 17 years of age and younger.2 In CAPS, Cathflo restored function in 83% (257/310) of central lines after up to 2 doses using a 120-minute dwell time for each.2 Adverse events that occurred in the study included catheter-related complications (1.3%),a sepsis (1.0%), and fever/lethargy (<1.0%).2 There were no reports of intracranial hemorrhage or embolic events with Cathflo in clinical trials, including infants as young as 2 weeks of age. Sepsis developed in 3 patients; each of these patients had evidence of infection prior to administration of Cathflo.2

CAPS was an open-label, single-arm trial that evaluated the safety of Cathflo in 310 patients between the ages of 2 weeks and 17 years.8 Cathflo was evaluated in a maximum of 2 doses at ≤2 mg per dose. The primary objective was to evaluate safety, as measured by the incidence of intracranial hemorrhage (ICH). Secondary objectives included assessing restoration rates at 30 minutes and 120 minutes, and serious adverse events within 48 hours.2

When administered for restoration of function to CVADs according to instructions, circulating plasma levels of alteplase are not expected to reach pharmacologic concentrations. If a 2-mg dose of Cathflo was administered by bolus injection into the circulation, the concentration of circulating drug would be expected to return to endogenous levels of 5 to 10 ng/mL within 30 minutes.8

Coverage

Medicare does not have a specific national coverage policy on Cathflo for the treatment of occluded CVADs, but local coverage determinations (LCDs) for some Medicare Administrative Contractors (MACs) support use of Cathflo.23 Additionally, the absence of a coverage policy does not mean noncoverage. In general, Medicare covers a drug used in the outpatient setting if it is not usually self-administered and its use is reasonable and necessary for treatment of the patient's condition.23

Most private payers do not have coverage policies related to the use of Cathflo for the treatment of occluded CVADs, but the absence of a coverage policy does not mean noncoverage. Please contact individual payers as necessary to determine their specific coverage guidelines.

Reimbursement

Reimbursement for all services, supplies, and drugs furnished to a Medicare beneficiary during an inpatient hospitalization is bundled into a single prospective payment under the Medicare Severity Diagnosis Related Group (MS-DRG) system. Cathflo is not separately reimbursed.

Cathflo is reimbursed at Average Sales Price (ASP) plus 6% when administered to Medicare beneficiaries in the outpatient hospital setting (ASP is published quarterly by the Centers of Medicare and Medicaid Services).

Cathflo is reimbursed at Average Sales Price (ASP) plus 6% when administered to Medicare beneficiaries in a physician’s office or freestanding clinic (ASP is published quarterly by the Centers of Medicare and Medicaid Services).

Genentech has established the Access to Care Foundation for each of its marketed products. The program is designed to provide products to patients who are uninsured or rendered uninsured due to payer denial and who meet the program's medical and financial criteria. For information on Genentech's Access to Care Foundation, please visit GenentechAccessSolutions.com

aAt least 1 due to catheter rupture.
bCPT is a registered trademark of the American Medical Association. Copyright 2011 American Medical Association. All rights reserved.

Important Safety Information

Indication

Cathflo® Activase® (alteplase) is indicated for the restoration of function to central venous access devices as assessed by the ability to withdraw blood.

Contraindications

Cathflo Activase should not be administered to patients with known hypersensitivity to alteplase or any component of the formulation.

Precautions

General

Certain causes of catheter dysfunction should be considered before treatment with Cathflo Activase (e.g. catheter malposition, mechanical failure, constriction by a suture and lipid deposits or drug precipitates within the catheter lumen). These types of conditions should be considered before treatment with Cathflo Activase.

Excessive pressure should be avoided when Cathflo Activase is instilled into the catheter. Such force could cause rupture of the catheter or expulsion of the clot into the circulation.

Bleeding

The most frequent adverse reaction associated with all thrombolytics in all approved indications is bleeding. Cathflo Activase has not been studied in patients known to be at risk for bleeding events that may be associated with the use of thrombolytics. Caution should be exercised with patients who have any condition for which bleeding constitutes a significant hazard.

Should serious bleeding in a critical location (e.g., intracranial, gastrointestinal, retroperitoneal, pericardial) occur, treatment with Cathflo Activase should be stopped and the drug should be withdrawn from the catheter.

Infections

Cathflo Activase should be used with caution in the presence of known or suspected infection in the catheter. Using Cathflo Activase in patients with infected catheters may release a localized infection into the systemic circulation. As with all catheterization procedures, care should be used to maintain aseptic technique.

Hypersensitivity

Hypersensitivity, including urticaria, angioedema and anaphylaxis, has been reported in association with use of Cathflo Activase. Monitor patients treated with Cathflo Activase for signs of hypersensitivity and treat appropriately if necessary.

Drug Interactions and Drug/Laboratory Test Interactions

The interaction of Cathflo Activase with other drugs has not been formally studied. Concomitant use of drugs affecting coagulation and/or platelet function has not been studied.

Potential interactions between Cathflo Activase and laboratory tests have not been studied.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential or the effect on fertility.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Cathflo Activase should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Adverse Reactions

In clinical trials, the most serious adverse events reported after treatment were sepsis, gastrointestinal bleeding, and venous thrombosis.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see accompanying full Prescribing Information for additional Important Safety Information.

    • Infusion Nurses Society. Infusion therapy standards of practice. J Infus Nurs. 2021:44(suppl 1):S1-S224.

      Infusion Nurses Society. Infusion therapy standards of practice. J Infus Nurs. 2021:44(suppl 1):S1-S224.

    • Blaney M, Shen V, Kerner JA, et al; for CAPS Investigators. Alteplase for the treatment of central venous catheter occlusion in children: results of a prospective, open-label, single-arm study (the Cathflo Activase Pediatric Study). J Vasc Interv Radiol. 2006;17(11, pt 1):1745-1751.

      Blaney M, Shen V, Kerner JA, et al; for CAPS Investigators. Alteplase for the treatment of central venous catheter occlusion in children: results of a prospective, open-label, single-arm study (the Cathflo Activase Pediatric Study). J Vasc Interv Radiol. 2006;17(11, pt 1):1745-1751.

    • Camp-Sorrell D, Matey L, ed. Access Device Standards of Practice for Oncology Nursing. 4th ed. Oncology Nursing Society; 2017.

      Camp-Sorrell D, Matey L, ed. Access Device Standards of Practice for Oncology Nursing. 4th ed. Oncology Nursing Society; 2017.

    • McKnight S. Nurse's guide to understanding and treating thrombotic occlusion of central venous access devices. Medsurg Nurs. 2004;13(6):377-382.

      McKnight S. Nurse's guide to understanding and treating thrombotic occlusion of central venous access devices. Medsurg Nurs. 2004;13(6):377-382.

    • Haire WD, Herbst SF. Consensus conference on the use of alteplase (t-PA) for the management of thrombotic catheter dysfunction. J Vasc Access Devices. 2000;5(2):28-36.

      Haire WD, Herbst SF. Consensus conference on the use of alteplase (t-PA) for the management of thrombotic catheter dysfunction. J Vasc Access Devices. 2000;5(2):28-36.

    • AVA. Study Guide for Vascular Access Certification. Association for Vascular Access; 2011:iii-164.

      AVA. Study Guide for Vascular Access Certification. Association for Vascular Access; 2011:iii-164.

    • Cummings-Winfield C, Mushani-Kanji T. Restoring patency to central venous access devices. Clin J Oncol Nurs. 2008;12(6):925-934.

      Cummings-Winfield C, Mushani-Kanji T. Restoring patency to central venous access devices. Clin J Oncol Nurs. 2008;12(6):925-934.

    • Cathflo Prescribing Information. Genentech USA, Inc.

      Cathflo Prescribing Information. Genentech USA, Inc.

    • Siegel JD, Rhinehart E, Jackson M, Chiarello L; Healthcare Infection Control Practices Advisory Committee (HICPAC). Guidelines for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings. 2007:1-226.

      Siegel JD, Rhinehart E, Jackson M, Chiarello L; Healthcare Infection Control Practices Advisory Committee (HICPAC). Guidelines for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings. 2007:1-226.

    • Deitcher SR, Fesen MR, Kiproff PM, et al; for the Cardiovascular Thrombolytic to Open Occluded Lines-2 Investigators. Safety and efficacy of alteplase for restoring function in occluded central venous catheters: results of the Cardiovascular Thrombolytic to Open Occluded Lines trial. J Clin Oncol. 2002;20(1):317-324.

      Deitcher SR, Fesen MR, Kiproff PM, et al; for the Cardiovascular Thrombolytic to Open Occluded Lines-2 Investigators. Safety and efficacy of alteplase for restoring function in occluded central venous catheters: results of the Cardiovascular Thrombolytic to Open Occluded Lines trial. J Clin Oncol. 2002;20(1):317-324.

    • Doellman D, Buckner JK, Garrett JH Jr, et al. Best practice guidelines in the care and maintenance of pediatric central venous catheters. 2015. http://www.ivas.online/newstyle/wp-content/uploads/2019/06/AVA-Pediatric-Guidelines-2nd-edition_web.pdf

      Doellman D, Buckner JK, Garrett JH Jr, et al. Best practice guidelines in the care and maintenance of pediatric central venous catheters. 2015. http://www.ivas.online/newstyle/wp-content/uploads/2019/06/AVA-Pediatric-Guidelines-2nd-edition_web.pdf

    • Frey AM. Intravenous therapy in children. In: Hankins J, Lonsway RAW, Hedrick C, Perdue M, eds. Infusion Therapy in Clinical Practice. 2nd ed. WB Saunders; 2001:561-591.

      Frey AM. Intravenous therapy in children. In: Hankins J, Lonsway RAW, Hedrick C, Perdue M, eds. Infusion Therapy in Clinical Practice. 2nd ed. WB Saunders; 2001:561-591.

    • Richardson D. Vascular access nursing: standards of care, and strategies in the prevention of infection: a primer on central venous catheters (part 2 of a 3-part series). JAVA. 2007;12(1):19-27.

      Richardson D. Vascular access nursing: standards of care, and strategies in the prevention of infection: a primer on central venous catheters (part 2 of a 3-part series). JAVA. 2007;12(1):19-27.

    • Mohiaddin RH, Wann SL, Underwood R, Firmin DN, Rees S, Longmore DB. Vena caval flow: assessment with cine MR velocity mapping. Radiology. 1990;177(2):537-541.

      Mohiaddin RH, Wann SL, Underwood R, Firmin DN, Rees S, Longmore DB. Vena caval flow: assessment with cine MR velocity mapping. Radiology. 1990;177(2):537-541.

    • Raaf JH. Results from use of 826 vascular access devices in cancer patients. Cancer. 1985;55(6):1312-1322.

      Raaf JH. Results from use of 826 vascular access devices in cancer patients. Cancer. 1985;55(6):1312-1322.

    • Stephens LC, Haire WD, Kotulak GD. Are clinical signs accurate indicators of the cause of central venous catheter occlusion? J Parenter Enteral Nutr. 1995;19(1):75-79.

      Stephens LC, Haire WD, Kotulak GD. Are clinical signs accurate indicators of the cause of central venous catheter occlusion? J Parenter Enteral Nutr. 1995;19(1):75-79.

    • National Institutes of Health. Management of central venous catheter occlusions. Pharm Update. 1999:1-4.

      National Institutes of Health. Management of central venous catheter occlusions. Pharm Update. 1999:1-4.

    • Ryder M. The role of biofilm in vascular catheter-related infections. N Dev Vasc Dis. 2001;2:15-25.

      Ryder M. The role of biofilm in vascular catheter-related infections. N Dev Vasc Dis. 2001;2:15-25.

    • Hadaway LC. Reopen the pipeline for IV therapy. Nursing. 2005;35(8):54-61.

      Hadaway LC. Reopen the pipeline for IV therapy. Nursing. 2005;35(8):54-61.

    • Wingerter L. Vascular access device thrombosis. Clin J Oncol Nurs. 2003;7(3):345-348.

      Wingerter L. Vascular access device thrombosis. Clin J Oncol Nurs. 2003;7(3):345-348.

    • Kaler W, Chinn R. Successful disinfection of needleless access ports: a matter of time and friction. JAVA. 2007;12(3):140-142.

      Kaler W, Chinn R. Successful disinfection of needleless access ports: a matter of time and friction. JAVA. 2007;12(3):140-142.

    • Ponec D, Irwin D, Haire WD, et al. Recombinant tissue plasminogen activator (alteplase) for restoration of flow in occluded central venous access devices: a double-blind placebo-controlled trial—the cardiovascular thrombolytic to open occluded lines (COOL) efficacy trial. J Vasc Inter Radiol. 2001;12(8):951-955.

      Ponec D, Irwin D, Haire WD, et al. Recombinant tissue plasminogen activator (alteplase) for restoration of flow in occluded central venous access devices: a double-blind placebo-controlled trial—the cardiovascular thrombolytic to open occluded lines (COOL) efficacy trial. J Vasc Inter Radiol. 2001;12(8):951-955.

    • Criddle LM. Ask the experts. Crit Care Nurse. 2007;27(3):78-81.

      Criddle LM. Ask the experts. Crit Care Nurse. 2007;27(3):78-81.