Methods for treating sepsis

Abstract

The present invention provides a method of treatment for patients with sepsis. The claimed treatment is a combination therapy with protein C and BPI protein. Combining protein C, with its anti-coagulant/anti-inflammatory properties, and BPI, with its bactericidal and endotoxin neutralizing activities, provides an effective, synergistic therapy for sepsis that will reduce or ameliorate the adverse events and improve the clinical outcome of septic patients.

We claim:  
     
         1 . A method of treating a patient suffering from sepsis which comprises, administering to said patient a pharmaceutically effective amount of protein C in combination with bactericidal/permeability-increasing (BPI) protein.  
     
     
         2 . The method of  claim 1 , wherein said patient is human.  
     
     
         3 . The method of  claim 1  wherein the protein C is human protein C zymogen.  
     
     
         4 . The method of  claim 1  wherein the protein C is human activated protein C.  
     
     
         5 . The method according to  claim 4 , wherein the amount of human activated protein C is about 1 μg/kg/hr to about 50 μg/kg/hr.  
     
     
         6 . The method of  claim 5 , wherein the human activated protein C is administered by continuous infusion for about 1 to about 240 hours.  
     
     
         7 . The method of  claim 1 , wherein the BPI protein is administered by bolus injection.  
     
     
         8 . The method of  claim 7 , wherein the amount of BPI protein is about 0.1 mg/kg to about 10 mg/kg of body weight.  
     
     
         9 . The method of  claim 1 , wherein the BPI protein is administered by continuous infusion or about 1 to about 240 hours.  
     
     
         10 . The method of  claim 9 , wherein the amount of BPI protein is about 4 μg/kg/hr to about 420 μg/kg/hr.  
     
     
         11 . A method of treating sepsis in a patient in need thereof, which comprises administering to said patient a pharmaceutically effective amount of BPI protein and activated protein C such that activated protein C plasma level of about 2 ng/ml to about 300 ng/ml is achieved.  
     
     
         12 . The method of  claim 11  wherein the activated protein C is administered in a bolus injection.  
     
     
         13 . The method of  claim 11  wherein the activated protein C is administered by continuous infusion for about 1 to about 240 hours.  
     
     
         14 . The method of  claim 11  wherein the activated protein C is administered first as a bolus then as a continuous infusion.  15 . The method of  claim 14  wherein one third of the activated protein C required to achieve activated protein C plasma levels in the range of about 2 ng/ml to about 300 ng/ml is administered in a bolus injection followed by continuous infusion of the remaining two thirds of the activated protein C.