Double-blind, randomized comparison of systemic continuous infusion of 0.25 versus 0.50 mg/kg/24 h of alteplase over 3 to 7 days for treatment of deep venous thrombosis in heparinized patients: results of the European Thrombolysis with rt-PA in Venous Thrombosis (ETTT) trial.
Thirty-two patients with acute, proximal-vein thrombosis were treated with heparin and alteplase (0.25 versus 0.5 mg/kg/24 h during 3-7 days) in a randomized, double-blind, multicenter, European (ETTT) trial. The treatment resulted in a decrease of the venographic Marder's score from 18 (6-25) to 13 (2-24) units (median, range) in Group I (0.25 mg/kg/24 h, n = 15, median decrease 3.0, p = 0.32) and from 17.5 (3-33) to 15.5 (0-27) in Group II (0.5 mg/kg/24 h, n = 16, median decrease 4.0, p = 0.23). Comparison of the sequential venograms could be performed in 14 cases of Group I and in 15 cases in Group II. A minority of patients showed substantial partial recanalization of the initially obstructed veins on the control venogram (one in each treatment group) and most of the control venograms showed either thrombus size reductions (5 in Group I, 7 in Group II) or no change or even deterioration (8 in Group I, 7 in Group II). Major bleedings were observed in 7 patients (7/32, 22%), 5 of them occurring in Group II (5/17, 29%). Thus, the results of the ETTT trial show that the used low dosages of alteplase administered intravenously over 3-7 days in heparinized patients cannot be recommended as a treatment for patients with deep venous thrombosis of lower limbs and/or pelvis. Further studies are needed to define a more suitable dosage regimen of alteplase in this indication.
Bounameaux
H
H
Department of Medicine, University Hospital of Geneva, Switzerland.
Banga
J D
JD
Bluhmki
E
E
Coccheri
S
S
Fiessinger
J N
JN
Haarmann
W
W
Lockner
D
D
Mahler
F
F
Ninet
J
J
Schneider
P A
PA
D000293:Adolescent; D000328:Adult; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000517:prevention & control*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D013924:Thrombophlebitis / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
D011994:Recombinant Proteins; D006493:Heparin; D010959:Tissue Plasminogen Activator