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coronary artery patency (TIMI flow grade 3) at coronary
angiography performed 60 min after amediplase adminis-
tration. Efficacy was also evaluated as corrected TIMI frame
count at 60 min, resolution of ST elevation at 180 min after
amediplase administration, 30-day mortality and incidence
of in-hospital major nonfatal cardiovascular events. Safety
was evaluated by incidence and severity of adverse events
(including intracranial hemorrhages, major bleedings, and
minor bleedings) vital signs, laboratory tests, and ECG
recording. The pharmacokinetics and potential immunoge-
nicity of amediplase and the effect on the coagulation system
were also assessed in a subgroup of patients.
A total of 240 patients (120 in each treatment group) were
randomized (ITT population) and all of them received the
study drug (safety population). For the per-protocol (PP)
population, 108 patients were included in Group A and 104
patients in Group B. Results of the 60-min angiograms by
amediplase dose are summarized in Table 33.7.
A TIMI flow grade 3 was achieved in more than half of
patients (53% at 1mg/kg and 58% at 1.2mg/kg). No signifi-
cant differences were found between the two dose levels
regarding the incidence of different grades of coronary
artery patency. The mean corrected TIMI frame count at
1mg/kg (50.01
TABLE 33.8 3K2 Study: Resolution of ST Elevation at 3 h by
Amediplase Dose
Amediplase
1.0mg/kg
(N ¼ 120)
Amediplase
1.2mg/kg
(N ¼ 120)
Sum of ST elevations at baseline
N
45
57
Mean SD
1.48 0.85
1.45 0.81
Range
0.37- 4.12
0.32-3.58
Sum of ST elevations at 3 h postdose
N
45
53
Mean SD
0.46 0.36
0.62 0.48
Range
0.00-1.64
0.02-2.09
Schroeder's 3-component definition
Complete ( 70%) ST
elevation resolution
26 (58%)
19 (36%)
Partial (30-69%) ST
elevation resolution
7 (16%)
11 (21%)
No ( 29%) ST
elevation resolution
12 (27%)
23 (43%)
There was no difference between the two amediplase
dose groups regarding 30-day mortality: 5 patients (4%) in
Group A and 6 patients (5%) in Group B. No differences
were also found with regard to nonfatal cardiovascular
events and parameters of the coagulation system.
Pharmacokinetic, haemostasis, and immunogenicity
parameters were also investigated in a subgroup of patients.
The pharmacokinetic parameters (median, range) are sum-
marized in Table 33.9. There were no differences between
doses for all the considered parameters (except for AUC, as
expected) [27].
Haemostasis parameters are summarized in Table
33.10. A marked decrease in plasminogen and increase
in plasmin- a 2-antiplasmin complexes confirmed the high
fibrinolytic activity of amediplase. The fibrin specificity of
amediplase is suggested by the marked increase in D-dimer
and by the parallel consumption of a -2-antiplasmin. PAI-1
36.92)
were comparable. At 3 h after amediplase administration,
there was a greater proportion of patients with complete
(
37.95) and at 1.2mg/kg (46.38
70%) ST elevation resolution in Group A (58%) than in
Group B (36%) (Table 33.8).
TABLE 33.7 3K2 Study: Results of the 60-min Coronary
Angiogram by Amediplase Dose
Number of patients (% ITT)
Amediplase 1.0mg/kg
(N ¼ 120)
Amediplase 1.2mg/kg
(N ¼ 120)
Is Infarct-related artery identifiable? a
Yes
116 (97%)
118 (98%)
No
3 (3%)
2 (2%)
If yes, type
Right coronary
60 (52%)
56 (47%)
Left anterior
descending
41 (35%)
49 (42%)
TABLE 33.9 3K2 Study: Median (Range) of
Pharmacokinetic Parameters by Amediplase Dose
Left circumflex
11 (9%)
11 (9%)
Left main
1 (1%)
1 (1%)
Amediplase
1.0mg/kg (N
Amediplase
1.2mg/kg (N
Other
3 (3%)
1 (1%)
¼ 13)
¼ 9)
TIMI flow grade achieved b
Grade 0 21 (18%) 24 (20%)
Grade 1 9 (8%) 5 (4%)
Grade 2 24 (21%) 20 (17%)
Grade 3 62 (53%) 69 (58%)
a One patient died before undergoing coronary angiogram.
b TIMI flow grading as performed by a centralized expert panel; in one
patient, only the local TIMI flow evaluation at performing institution was
available.
Co ( m g/mL)
20.5 (11.7-47.5)
22.1 (15.4-47.1)
AUC
( m g/mL
408 (194-825)
542 (212-935)
min)
t 1/2 a (min)
11.5 (8.5-21.1)
14.1 (7.1-21.6)
t 1/2 b (min)
100 (55-581)
125 (73-824)
CL (mL/min kg)
2.5 (1.2-5.1)
2.2 (1.3-5.7)
V c (mL/kg)
48.8 (21.0-85.5)
54.2 (25.5-77.8)
V area (mL/kg)
400 (173-2053)
401 (151-2376)
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