[Results of the North Baden Venous Lysis--NBVL--Study. Prospective phlebographically controlled randomized multicenter evaluation of ultra high versus conventional dose streptokinase in acute thrombosis of the leg and pelvic veins].

BACKGROUND AND AIM: The Nordbaden Multicentre Study on lysis of venous thrombosis was prompted by a lack of randomized studies comparing ultra-high and conventional-dose streptokinase therapy in fresh iliac and leg vein thrombosis. The aim was to compare prospectively the phlebographically monitored results of three courses of ultra-high dosed with those of a 5-day course of conventionally dosed streptokinase treatment and to record any side-effects of fibrinolysis.

PATIENTS AND METHOD: 77 patients were randomized to ultra-high-dose streptokinase (group A), and 79 to conventionally-dosed streptokinase (group B) therapy. In 13 patients of group A and 10 of group B, no monitoring phlebography was possible--in 15 patients (9.6%) who broke off treatment prematurely, and in 8 (5.1%) who failed to keep their phlebography appointment.

RESULTS: Detailed analysis of the phlebographic findings (main target criterion) on the basis of the IFP score revealed a decrease in the score from 4.55 to 2.41 (47%) for the 64 group A patients after a mean of 2.7 +/- 0.6 courses of treatment with administration of 24 +/- 5.7 million IU streptokinase, and from 4.2 to 2.93 (30%) for the 69 group B patients after a mean of 3.7 +/- 1.2 days of treatment with administration of 8.6 +/- 3.3 million IU (p = 0.007). Of the 281 totally occluded vein segments in group A, 132 (47%) were rendered fully patent, while this was true of 81 (29%) of the 279 total occlusions in group B. Of the 21 incomplete occlusions in each group, 10 in group A and 16 in group B became fully patent. Analysis of subgroups and individual factors showed that the re-establishment of patency in the 45 men in group A was better (55%) than in the 47 group B men (30%); while the women showed no inter-group difference there was an overall difference vis-a-vis the men (p = 0.02). In group A, patients aged over 60 showed better results (61%) than those of the same age in group B (20%) (p = 0.003). The presumably older thrombi were just as readily lysable as fresher ones. Among the 77 group A patients, side-effects occurred significantly less frequently than among the 79 group B patients. For the most part, side-effects were haemorrhage overall (22.1% vs. 35.7%) and urogenital bleeding in particular (6.5% vs. 22.8%); there were no deaths. Women bled somewhat more often than men (35.2% vs. 26.5%), and bleeding was more commonly in patients older than 65 years.

CONCLUSIONS: 1. Ultra-high-dose streptokinase treatment of deep venous thrombosis (iliac, femoral, popliteal veins) is more effective (at least in males) and produces less bleeding than conventional doses. 2. Presumably older thromboses (8 to 14 days) are no less responsive to ultra-high dose streptokinase. 3. In view of the higher risk of bleeding in over-65-year-olds, the indication for fibrinolytic therapy must be considered with care.