Clinical trial of brinase and anticoagulants as a method of treatment for advanced limb ischemia.

A randomized, single-blind trial of repeated intravenous infusion of Brinase was carried out in 70 petients with severe chronic limb ischemia, who were candidates for lumbar sympathectomy or amputation. The enzyme caused s significant increase in calf and ankle pressure index. At six months follow-up, the clinical results were statistically significant in favour of Brinase when all patients were considered, but not if 10 patients with Buerger's disease were omitted from the analysis. Patients treated with a combination of Brinase and coumarins had a better clinical outcome than patients receiving either treatment on its own.

Relief of chronic arterial obstruction using intravenous brinase. A control study.

A therapeutic trial using placebo or the thrombolytic enzyme brinase was carried out in a group of patients with chronic arterial obstruction. The patients were observed for 3 months before receiving six intravenous infusions of either saline or brinase over a period of 2 weeks. Ankle blood pressure, Doppler ultrasound scanning, and arteriography were used to establish diagnosis in the patients. No changes were observed during the 3-month pre-observation period. After six brinase infusions, recanalization of 17 out of 27 obstructed arterial segments was recorded and the number of patent segments increased from 11 to 27. No improvement was observed in the placebo-treated patients. The differences between brinase and placebo treatment was statistically significant.

Local treatment of recent arterial thromboembolic occlusions with brinase.

Brinase was administered intra-arterially in 16 patients with thrombotic or embolic arterial occlusions. Angiography could be performed before and after treatment in 13 patients. Thrombolysis was obtained in 3 of 9 patients with thrombotic and in 3 of 4 patients with embolic occlusions. In 3 patients severe local side effects occurred.

Thrombolytic treatment with i.v. brinase of advanced arterial obliterative disease of the limbs.

The material includes 17 patients suffering from different degrees of chronic peripheral arterial disease (11 chronic patients stage III and IV, two patients with acute arterial occlusion, and four patients stage II). Presence and extent of arterial occlusion was ascertained by initial arteriography. In twelve of the patients amputation had been considered. The patients were treated by a series of i.v. infusions of brinase, a proteolytic enzyme from Aspergillus oryzae. The brinase inhibitor capacity in plasma was determined by the azocollagen technique. Dosage of brinase was calculated to retain a rest-inhibitor capacity in order to avoid free proteolytic activity. In five patients the enzyme was also given preoperatively by intra-arterial instillation prior to a series of i.v. brinase infusions. Thirteen patients showed clinical improvement after brinase treatment. The condition of two patients remained unchanged, and in two patients amputation could not be avoided. In fourteen patients the treatment results were followed by measurement of peripheral systolic blood pressure. In ten patients obvious increase of the peripheral systolic blood pressure was observed. Cutaneous microcirculation was studied in seven patients by i.v. sequential fluorescein angiography and signs of improved microcirculation (appearance time, intensity and/or extent of fluorescence) were found in all examined patients. One patient with acute arterial occlusion of the right leg with obstruction of blood flow from the external iliac artery showed complete disobliteration after a series of i.v. brinase infusions. Bleeding complications associated with brinase treatment were not observed in the material. In three patients brinase treatment was discontinued because of complications (2 brinase, 1 heparin).