Collaborative angiographic patency trial of recombinant staphylokinase (CAPTORS).
BACKGROUND
We undertook an angiographic, dose-finding study of staphylokinase (SAK42D variant) to evaluate its efficacy and safety in patients with acute ST-segment myocardial infarction.


RESULTS
Patients were studied within 6 hours of symptom onset and received SAK42D as a 30-minute infusion with 20% of the total dose given as a bolus. Eighty-two patients with a median age of 60 years (interquartile range 52 to 69 years), 84% male and 43% with an anterior myocardial infarction, were studied at a median time from symptom onset of 2.7 hours. There was a high degree of Thrombolysis in Myocardial Infarction (TIMI) 3 flow achieved with 15 mg of SAK42D, that is, 62%. Therefore after 21 patients had been studied at this dose the next dose of 30 mg was used and 65% TIMI 3 patency was achieved. At the peak dose of 45 mg, TIMI 3 90-minute patency was 63%. There were no allergic reactions, and no patient had intracranial hemorrhage. Four patients had major and 9 moderate bleeding during the study; 2 of the major and 5 of the moderate bleeding events occurred within 48 hours of commencement of treatment. The majority (62%) of these were related to vascular instrumentation, and there was no relation between the extent of bleeding and dose of SAK42D used. Forty-five minutes after cessation of SAK42D, there were small percent decrements in plasma fibrinogen and plasminogen levels that did not reach statistical significance. However, there were dose-related changes in alpha(2) anti-plasmin that revealed a borderline significant reduction that was dose related (P =.053).


CONCLUSIONS
These data revealed similar fibrinolytic efficacy across a 3-fold increment in dose, indicating that this study operated on a flat portion of the dose-response curve. The favorable efficacy/safety profile achieved with staphylokinase is encouraging, and further investigation is warranted.
Armstrong
P W
PW
University of Alberta, Edmonton, Canada. paul.armstrong@ualberta.ca
Burton
J R
JR
Palisaitis
D
D
Thompson
C R
CR
Van de Werf
F
F
Rose
B
B
Collen
D
D
Teo
K K
KK
D000368:Aged; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008666:Metalloendopeptidases / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D015912:Thrombolytic Therapy; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus