Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis. Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial and graft occlusions: a randomized trial. Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoropopliteal occlusions: a prospective, randomized multicenter trial. Surgical treatment versus thrombolysis in acute arterial occlusion: a randomised controlled study. Comparative results of thrombolysis treatment with rt-PA and urokinase: a pilot study. Hyperbaric oxygen and thrombolysis in myocardial infarction: the 'HOT MI' randomized multicenter study. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Tissue plasminogen activator for the treatment of acute pulmonary embolism. A collaborative study by the PIOPED Investigators.
Sixty patients were recruited into a randomized parallel group comparison of three thrombolytic regimens for acute or subacute peripheral arterial thrombosis. There were no significant differences in age, duration of history, length of occlusion or presence of neurosensory deficit between the groups. Initially successful lysis was significantly greater with intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) than with either streptokinase (Sk) (P less than 0.04) or intravenous (IV) rt-PA (P less than 0.01). The duration of therapy varied from a median of 35 h with IA rt-PA to 40 h with Sk (P greater than 0.5). The median (confidence interval) increase in ankle:brachial pressure index following IA rt-PA of 0.57 (0.33-0.82) was significantly higher than for either Sk of 0.24 (0-0.57) or for IV rt-PA of 0.18 (0-0.41). Limb salvage at 30 days was achieved in 80, 60 and 45 per cent respectively for IA rt-PA, Sk and IV rt-PA. Haemorrhagic complications occurred in six patients following Sk and in 13 following IV rt-PA; only one minor haemorrhage occurred following a catheter perforation in a patient who received IA rt-PA (P less than 0.05). IA rt-PA provides a more effective, safer fibrinolytic regimen than conventional therapy with Sk. IV rt-PA has not been as successful and carries a significantly higher risk of haemorrhagic complications. A randomized prospective trial was undertaken to compare intraarterial administration of recombinant human tissue-type plasminogen activator (rt-PA) with urokinase (UK) in 32 patients with peripheral arterial or bypass graft occlusions. Sixteen patients were randomized to receive rt-PA and 16 to receive UK. The rt-PA dose was administered as a 10-mg bolus into the thrombus, followed by 5 mg/h for up to 24 hours. The UK dose was administered as a 60,000 IU bolus into the thrombus, followed by 240,000 IU/h for 2 hours, 120,000 IU/h for 2 hours, and 60,000 IU/h for up to 20 hours. Serial arteriograms were obtained at baseline and at 4, 8 or 16, and 24 hours. The endpoint was defined as 95% of greater clot lysis. The cumulative numbers of patients with successful thrombolysis (rt-PA vs UK) were four vs none at 4 hours, seven vs one at 8 hours, seven vs three at 16 hours, and eight vs six at 24 hours. Lysis occurred more rapidly in the rt-PA group (P = .04). Major bleeding complications occurred in five rt-PA patients and two UK patients (P = .39). At 24 hours, fibrinogen levels were significantly lower in the rt-PA group than in the UK group (P = .01). There was no apparent difference in 30-day clinical success. To determine the effect of intravenous recombinant tissue plasminogen activator (rt-PA) on vascular and neurologic outcomes, we enrolled 31 patients with acute carotid artery-territory ischemic stroke within 6 hours from symptom onset in a randomized, double-blind, placebo-controlled study. We gave either rt-PA (duteplase at the dose of 20 or 30 mega-international units [MIU]) or placebo intravenously for 60 minutes in patients randomly assigned to the three groups. A comparison between the baseline and postinfusion angiograms showed that complete or partial reperfusion occurred in 50% (5/10) of patients treated with 30 MIU rt-PA, 44% (4/9) of those treated with 20 MIU rt-PA, and 17% (2/12) in the control group. In patients with middle cerebral artery occlusions, reperfusion occurred in 71% (5/7) of the 30-MIU group, in 67% (4/6) of the 20-MIU group, and in 13% (1/8) of the control group. Patients treated with 30 MIU rt-PA showed a significantly early and better clinical improvement, as measured by the neurologic scale, than did those treated with placebo. Parenchymal hemorrhage occurred in one patient in each group, and frequency of clinically insignificant hemorrhagic infarction was comparable among the treatment groups. No major systemic complications occurred in any group. These results support the efficacy of intravenous infusion of rt-PA soon after the onset of stroke in producing rapid thrombolysis and neurologic recovery; it may be of particular value in patients with thromboembolic occlusion in the middle cerebral artery. To report the outcome of a prospective, randomized, open multicenter trial comparing (1) the effects of local thrombolysis with recombinant tissue plasminogen activator (rtPA) or urokinase (UK) and (2) 2 administration techniques.
                Two hundred thirty-four patients with thromboembolic occlusions in 223 native femoral or popliteal arteries (95%) and 11 bypass grafts (5%) were randomized to rtPA (n = 124) or UK (n = 110) administered either through an endhole catheter (Hess technique) in 81 patients or a microporous balloon catheter (Schneider technique) in 153 patients. When lysis was incomplete, additional catheter interventions were applied to achieve patency. Results were analyzed by fluoroscopy during intervention and by angiography evaluated by independent experts blinded to the methods applied.
                The only significant difference between rtPA and UK was found at the end of lysis using the Hess technique. Complete reperfusion (TIMI grade 3) was produced in 60% of patients by rtPA versus 37% by UK (p = 0.045). By both techniques TIMI grade 3 was achieved in 62% with rtPA and in 50% with UK (p = 0.18). Independent of delivery technique, thrombolytic agent, or additional catheter interventions, TIMI grade 3 was achieved in 81% and angiographic patency in 88%. Primary patency at 6 months was 66%, which was increased by secondary interventions to 75%. Major amputations were performed in 6%, all in patients with initial Fontaine stage III/IV ischemia.
                With local thrombolysis alone, rtPA appears to be more effective than UK; however, additional catheter interventions further improved patency, abolishing the difference between the lytic agents. Thrombolytic treatment has been tried in various forms for acute limb ischaemia with varying degrees of success but is also often accompanied by bleeding problems. The present investigation compares the effect of surgical thrombectomy (TE) and thrombolysis (TL) using recombinant tissue plasminogen activator (rt-PA). Twenty patients with a need for intervention owing to ischaemia lasting more than 24 h but less than 14 days were included. Patients randomised to TE were operated under epidural anaesthesia and patients in the TL group received 30 mg rt-PA during a 3 h period through a catheter placed into the thrombus and advanced as lysis was achieved. Thrombectomy resulted in an immediate restitution of blood flow in six out of nine cases, in three cases a bypass procedure was performed, and one of these failed with a resultant amputation. Thrombolysis gave a good primary result in six cases which lasted in four of them. Three had a subsequent percutaneous transluminal angioplasty. Partial lysis was seen in two cases and a further two failed. Five went to surgery with three bypass and two fogarty procedures being necessary. There was no hospital mortality and there were no bleeding complications due to the rt-PA treatment in this series. In 19 out of 20 patients the circulation was re-established. Appropriate handling of acute ischaemic conditions implies the use of both thrombolysis and appropriate surgical procedures, including distal bypass grafts. The aim of the following prospective study was to investigate whether patients benefited from locoregional lysis treatment of recent deep leg vein thrombosis after 1 year.
                The prospective study included 69 patients aged between 22 and 58 years, in whom recent lower leg vein and popliteal vein thromboses were diagnosed by phlebography. Patients were randomized to one of three treatment groups: one group was treated for a maximum of 7 days with full heparinization and daily dose of 20 mg rt-PA administered locoregionally over a period of 4 hours; a second group received 100,000 IU/h urokinase locoregionally for a maximum of 7 days, in addition to full heparinization; and in the third group (control group), intravenous heparin infusions after PTT constituted the only form of treatment. All patients were given phenprocoumon from day 7 and received compression treatment. Before treatment began and before the course of phenprocoumon started, phlebography and colour duplex sonography examinations were carried out. After 12 months, follow-up duplex sonography was conducted to evaluate the reflux times over the popliteal vein and the degree of patency of the deep leg veins.
                Complete lysis was achieved in 6 of 22 patients in the recombinant tissue plasminogen activator (rt-PA) group and in 11 of 22 patients in the urokinase group. At follow-up examination after 12 months, there were serious post-thrombotic changes in 14 of 22 patients in the rt-PA group, in 9 of 22 patients in the urokinase group and in 15 of 22 patients in the group of patients who received no lysis treatment.
                Patients with recently formed thromboses in the lower leg and popliteal veins who underwent 7 days of locoregional lysis treatment with urokinase demonstrated significantly fewer clinical symptoms of post-thrombotic syndrome after 1 year than those who received locoregional treatment with rt-PA over a similar period or a control group treated with anticoagulants only. In a previous pilot study, we demonstrated that adjunctive treatment with hyperbaric oxygen (HBO) appears to be feasible and safe in patients with acute myocardial infarction (AMI) and may result in an attenuated rise in creatine phosphokinase (CPK), more rapid resolution of pain and ST changes. This randomized multicenter trial was organized to further assess the safety and feasibility of this treatment in human subjects. Patients with an AMI treated with recombinant tissue plasminogen activator (rTPA) or streptokinase (STK), were randomized to treatment with HBO combined with either rTPA or STK, or rTPA or STK alone. An analysis included 112 patients, 66 of whom had inferior AMIs (p = NS). The remainder of the patients had anterior AMIs. The mean CPK at 12 and 24 h was reduced in the HBO patients by approximately 7.5% (p = NS). Time to pain relief was shorter in the HBO group. There were 2 deaths in the control and 1 in those treated with HBO. The left ventricle ejection fraction (LVEF) on discharge was 51.7% in the HBO group as compared to 48.4% in the controls (p = NS). The LVEF of the controls was 43.4 as compared to 47.6 for those treated, approximately 10% better (no significant difference). Treatment with HBO in combination with thrombolysis appears to be feasible and safe for patients with AMI and may result in an attenuated CPK rise, more rapid resolution of pain and improved ejection fractions. More studies are needed to assess the benefits of this treatment. Experiments in animals have demonstrated that recombinant tissue plasminogen activator (rt-PA) produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated, and bleeding is reduced when rt-PA is administered over a short period. In previous studies in patients with thrombotic disease, rt-PA has been shown to be an effective thrombolytic agent when administered by continuous infusion over a period between 90 minutes and 8 hours. To determine whether a short course regimen of rt-PA can achieve thrombolysis, a double-blind randomized trial has been conducted in which patients with objectively established acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-minute infusion of rt-PA at a dose of 0.6 mg/kg (33 patients) or saline placebo (25 patients). Perfusion lung scanning was used to assess the change in pulmonary perfusion at 24 hours and seven days post-study drug administration. Thirty-four percent of the rt-PA patients had a greater than 50 percent resolution in the perfusion defect at 24 hours compared to 12 percent of placebo patients (p = 0.026). At 24 hours, the mean relative improvement in the perfusion defect was 37.0 percent in rt-PA treated patients compared to 18.8 percent in the placebo group (p = 0.017). By day 7, no difference in lung scan resolution was detected between the groups. There were no major bleeds in either group nor were there any differences in transfusion requirements between groups. Minor bleeding occurred in 15 of the rt-PA patients mainly at angiogram-catheter insertion and venipuncture sites. These results suggest that a bolus regimen of rt-PA produces accelerated thrombolysis and provides an alternative and convenient approach to thrombolytic therapy in patients with pulmonary embolism. Thirteen patients with acute pulmonary embolism were treated in a randomized double-blind fashion either with recombinant tissue plasminogen activator (rt-PA) 40 to 80 mg, usually in combination with heparin, or with placebo plus heparin. The drug was administered intravenously over 40 to 90 minutes. Nine patients received rt-PA, and four received placebo. A lytic effect was observed 1.5 and three hours after the onset of therapy with rt-PA based upon elevated levels of fragment-D dimers. Among the patients who received rt-PA, there was a modest improvement of the total pulmonary resistance 1.5 hours after the start of therapy, but the angiograms showed no significant changes in two hours. After 24 hours, the lung scans showed a trend toward greater improvement with rt-PA, but the rate of improvement in comparison to control subjects was not statistically significant. Massive bleeding occurred in one patient. The observations in this study suggest that rt-PA has little effect in two hours on angiographic clot burden, but may produce some improvement in hemodynamics. The treatment, however, is not without risk.
There is some evidence to suggest that intra-arterial rt-PA is more effective than intra-arterial streptokinase or intravenous rt-PA in improving vessel patency in people with peripheral arterial occlusion. There was no evidence that rt-PA was more effective than urokinase for patients with peripheral arterial occlusion and some evidence that initial lysis may be more rapid with rt-PA, depending on the regime. Incidences of haemorrhagic complications were not statistically significantly greater with rt-PA than with other regimes. However, all of the findings come from small studies and a general paucity of results means that it is not possible to draw clear conclusions.