CSL Behring announced today that the first patient has been treated as part of the REPLACE Phase III clinical trial evaluating the efficacy and safety of fibrinogen concentrate (Human) (FCH) in controlling microvascular bleeding during aortic aneurysm surgery.
The purpose of this study is to demonstrate that Fibrinogen Concentrate (Human)(FCH) can reduce intraoperative bleeding and, therefore, the volume of donor blood products (e.g., fresh frozen plasma, platelets, and red blood cells) needed during complex cardiovascular surgical procedures such as aortic aneurysm surgery. The study will also aim to show that FCH is safe and well tolerated. The primary efficacy endpoint measurement will be the number of units of all allogeneic blood products transfused during the first 24 hours after administration of FCH or placebo.
"Potentially life-threatening bleeding events can occur during cardiovascular surgery because the patient’s fibrinogen levels are depleted, which delays clotting," said Dr. Niels Rahe-Meyer, Department of Anesthesiology and Intensive Care, Franziskus Hospital, Bielefeld, Germany and coordinating investigator of the study. "The REPLACE Phase III study will help determine if FCH treatment can safely reduce the number of transfusions needed during cardiovascular surgery. If this is the case, we will have a powerful new option for use in protecting cardiovascular surgery patients from potentially life-threatening bleeding and transfusion-associated adverse events and discomfort."
Of the 12 million units of blood used in the United States each year, 15 percent are used in cardiovascular surgery. Studies have shown that blood transfusion during or after adult cardiac surgery is associated with increased long-term mortality.
"As a global leader in the development of plasma-derived and recombinant coagulation factors for bleeding disorders, we are pleased that this important Phase III study of FCH in aortic aneurysm surgery is underway," said Russell Basser, M.D., Senior Vice President, Global Clinical R&D. "CSL Behring is committed to exploring the use of FCH in patients at high risk of bleeding resulting from cardiac surgery and providing optimal, uncompromised therapy to cardiac surgery teams and patients."
About the REPLACE Study
REPLACE (Randomized evaluation of fibrinogen versus placebo in complex cardiovascular surgery) is a Phase III, prospective, multinational, multicenter, randomized, double-blind, placebo-controlled, two-arm study. Patients undergoing elective thoracic aortic surgery are randomized in a 1:1 ratio to treatment with FCH or placebo. Patients will receive a single intra-operative infusion if their blood loss amounts to 60 to 250g in 5 minutes after initial surgery is completed. Following infusion, a second 5-minute bleeding mass measurement is undertaken. If blood loss then still amounts to 60 g or more, the patient will be treated according to a predefined, standardized treatment regimen using allogeneic blood products. Reduction of allogenic blood products and other efficacy endpoints in addition to safety endpoints will be measured according to the trial protocol. For more information visit www.clinicaltrials.gov and search with identifier: NCT01475669.
About Fibrinogen and Fibrinogen Concentrate
Fibrinogen, also called Factor I, is a protein needed to form blood clots and, thereby, to stop bleeding. Fibrinogen levels in plasma determine the potential clotting ability and activity in the body. Diminished concentrations of fibrinogen limit the body's ability to form a clot and increase the risk of uncontrolled bleeding. A simple blood test can detect the level of fibrinogen; the normal range is 2-4 grams per liter. In patients undergoing cardiopulmonary bypass surgery, the plasma concentration of fibrinogen has been reported to decrease by 34 to 42 percent, which can increase the risk of post-operative bleeding. During manufacture, CSL Behring’s purified, pasteurized, fibrinogen concentrate undergoes multiple steps to remove potential pathogens, including being heated in aqueous solution at 60 degrees centigrade/140 degrees Fahrenheit for 20 hours. A publication by the World Federation of Hemophilia provides additional perspective on this matter. Fibrinogen concentrate is mostly tolerated without undesirable reactions. In rare cases allergoid-anaphylactoid reactions (like generalized urticaria, rash, fall in blood pressure, dyspnoea), and/or rise in temperature are observed. If allergoid-anaphylactoid reactions occur, the administration of fibrinogen concentrate has to be discontinued immediately (e.g. by interruption of the injection/infusion) and an appropriate treatment has to be initiated. The current medical standards for shock treatment are to be observed. There is a potential risk of thromboembolic episodes (including myocardial infarction and pulmonary embolism) following the administration of human plasma fibrinogen concentrate.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV. These measures may possibly be of limited value against non-enveloped viruses such as HAV and parvovirus B19.
About CSL Behring
CSL Behring is a leader in the plasma protein therapeutics industry. Committed to saving lives and improving the quality of life for people with rare and serious diseases, the company manufactures and markets a range of plasma-derived and recombinant therapies worldwide. CSL Behring therapies are indicated for the treatment of coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies, hereditary angioedema and inherited respiratory disease. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in newborns. CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited (ASX: CSL), a biopharmaceutical company headquartered in Melbourne, Australia. For more information, visit www.cslbehring.com.
Sheila A. Burke, Director, Communications & Public Relations
Worldwide Commercial Operations