Clinical Trial: Response of Recombinant Antithrombin in Heparin Resistant Patients Undergoing Cardiac Surgery

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Response of Recombinant Antithrombin in Heparin Resistant Patients Undergoing Cardiac Surgery

Brief Summary: The objective of this study is to prospectively evaluate the response of recombinant antithrombin (rAT) (ATRYN) in patients who are heparin resistant and are scheduled to undergo cardiac surgery.

Detailed Summary:

AT is an α2-globulin that is produced primarily in the liver. It binds thrombin, as well as other serine proteases, factors IX, X, XI, and XII, kallikrein, and plasmin irreversibly, which neutralizes their activity. However, only inhibition of thrombin and factor Xa by AT has physiologic and clinical significance.1 AT deficiency may occur as a congenital or acquired deficiency. Acquired deficiencies are secondary to increased AT consumption, loss of AT from the intravascular compartment (renal failure, nephrotic syndrome) or liver disease (cirrhosis). A normal AT level is 80% to 120% with activity below 50% considered clinically important based on the risk of venous thrombosis in patients with congenital deficiency of AT.2 However, the risk of thrombosis is higher in congenital forms than acquired forms of AT deficiency.3, 4 Unfortunately, the only abnormal coagulation test associated with this condition is the assay for AT activity, which is diagnostic but not readily available.

Acquired deficiencies of AT are commonly encountered in cardiac surgical patients. Anticoagulation with heparin for CPB depends on AT to inhibit clotting as heparin alone has no effect on coagulation. Heparin catalyzes AT inhibition of thrombin over a 1000 fold by binding to a lysine residue on AT and altering its conformation. Thrombin actually attacks AT, disabling it, but in the process attaches AT to thrombin, forming a complex that can be detected and used to assess thrombin formation but has no activity. Thirty percent of AT is consumed during this process so AT levels are reduced temporarily. If AT levels are not restored, then a condition may arise called heparin resistance. There are other less frequent causes of heparin resistance besides AT deficiency such as platelets, fibrin, vascular surfaces and plasma proteins.5 There is no universally accepted definition of heparin resistanc
Sponsor: Mayo Clinic

Current Primary Outcome: Percentage of Patients Whose Activated Clotting Time (ACT) is Prolonged Beyond 480 Seconds With Recombinant Human Antithrombin Concentrate (rhAT) Administration [ Time Frame: 3 minutes after the initial dose of rhAT, Day 1 of the study ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome: Percentage of cardiopulmonary bypass patients who are heparin resistant [ Time Frame: 5 minutes after intravenous loading dose of heparin, Day 1 of the study ]

Information By: Mayo Clinic

Dates:
Date Received: February 7, 2012
Date Started: February 2012
Date Completion:
Last Updated: July 13, 2015
Last Verified: July 2015