Summary
The controlled clinical trials of thrombolytic agents in the United States have been
carried out in two phases, under the auspices of the National Heart and Lung Institute.
Phase I was devoted to the comparison of 12-hour Urokinase (12h–UK) followed by heparin
(H) with heparin alone in patients with acute pulmonary embolism (Walsh et al. 1969).
The results showed that patients treated with UK had more rapid and greater resolution
of pulmonary thromboemboli in the first twenty-four hours of therapy than patients
treated with H alone, as assessed by serial pulmonary angiography, hemodynamics and
lung scanning (The Urokinase Pulmonary Embolism Trial, 1970, 1973 ; Hyers et al. 1970).
Because of the relatively small size of the Trial and the low mortality of treated
pulmonary embolism, mortality differences were not sought - nor was one found. Although
there was early difference in amount of clot resolution, patients treated with H alone
showed similar improvement by two weeks.
The Phase II Urokinase-Streptokinase Pulmonary Embolism Trial (USPET) was begun to
assess the comparative results of UK and Streptokinase (SK) therapy. Because of favorable
results obtained with SK in other countries, it was deemed necessary to make this
comparison (Browse and James, 1964 ; Hirsh et al. 1968 ; Miller et al. 1969, 1971
; Chesterman et al. 1969). A third group, 12-hour UK, was added to relate this study
(24-hour UK and SK) with the Phase I results which employed only a 12-hour infusion
of UK. This Phase II Trial represents the first controlled, randomized study of UK
and SK in thromboembolic disorders.
