North Baden venous lysis trial (NBVL): multicentre prospective randomized phlebographically controlled trial on the effect of ultra-high versus conventional doses of streptokinase in fresh leg-pelvis venous thromboses.
Since no previous randomized comparison has been carried out between ultra-high and conventional dosage streptokinase therapy of fresh venous thromboses, the NBVL trial was carried out as a prospective, randomized, multicentre, phlebographically monitored comparison of the results and adverse effects of these two fibrinolytic treatment options. Using the normal exclusion criteria, 156 patients with a leg-pelvis venous thrombosis presumed to be a maximum of 14 days old were treated with 1.5 million U streptokinase/h for 6h daily (n = 77, group A) or conventional dosage with 100,000 U streptokinase per hour (n = 79, group B). There were 15 patients (eight in group A, seven in group B) who had to stop therapy prematurely, and eight patients (five in group A, three in group B) could not be evaluated because of incorrect monitoring times. The phlebograms were evaluated using IFP-C scores. These showed a reduction in the IFP score from 4.55 to 2.2 in the 64 patients in group A after a mean of 2.7 +/- 0.6 therapy cycles with administration of 24.4 +/- 5.7 million U streptokinase, i.e. 47% of the baseline value. The 69 patients in group B had a reduction in score from 4.2 to 2.93 after a mean of 3.7 +/- 1.2 days of treatment with administration of 8.6 +/- 3.3 million units, i.e. a fall of 30% in the baseline values (p = 0.007). There were 132 out of 281 completely occluded venous segments in group A (47%) and 81 out of 279 segments in group B (29%) that showed complete patency. Eight out of 27 three-segment occlusions in group A and only one of 26 in group B showed complete patency. The IFP score improved by 55% in the 45 men in group A, compared with only 30% in the 47 men in group B (p = 0.002). When both dosages are combined, men showed a greater improvement in IFP score than women (42 versus 29%; p = 0.02). The IFP score improved more in the 20 patients aged more than 60 years in group A than in the 19 patients aged over 60 years of age in group B (61 versus 20%; p = 0.003). No other significant differences in effect were seen on analysis of sub-groups and individual factors (sex, age, presumed age of thrombus and side of thrombosis). In the 77 patients in group A, haemorrhagic complications were less frequent than in the 79 patients in group B (22.1 versus 36.7%; p = 0.054), especially concerning urogenital haemorrhage (6.5 versus 22.8%; p = 0.004). Women were affected more frequently by haemorrhagic complications than men (35.2 versus 26.5%), and the 19 patients aged more than 65 years old were affected more than the 137 younger patients (21.1 versus 13.9%). There were no deaths, and clinically insignificant pulmonary emboli occurred three times. Ultra-high dosage streptokinase shows better and more rapid thrombolytic treatment for popliteal-femoral-iliac venous thromboses and causes fewer haemorrhagic complications than conventional dosage streptokinase. The better effect of ultra-high dosage can be observed particularly for three-segment occlusion as well as in male patients. In older patients, accurate diagnosis is required because of the higher rate of haemorrhagic complications.
Heinrich
F
F
Med. Clinic I. City Clinic, Karlsruhe, Germany.
Heinrich
U
U
D000328:Adult; D017677:Age Distribution; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D010388:Pelvis / Q000098:blood supply*; D010690:Phlebography; D011446:Prospective Studies; D017678:Sex Distribution; D013300:Streptokinase / Q000009:adverse effects / Q000627:therapeutic use*; D013924:Thrombophlebitis / Q000188:drug therapy*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D013300:Streptokinase