Diabetic Foot, Critical Limb Ischemia
Conditions
Brief summary
In this randomized clinical trial (RCT) the investigators are trying to find out whether a low-dose therapy with daily short infusions of urokinase using 10 to 21 doses over a maximum of 30 days is capable of prolonging the survival time without major amputation.
Detailed description
August-2 is a trial embedded in the August-1 registry study. All patients enrolled in August-2 are also part of August-1, but there will be patients who are documented in the register, but will not take part in August-2. The investigators want to find out to which extent the patients in the registry are representative to the overall population suffering from this condition and how the therapeutic success of other therapy regimes can be described.
Interventions
DRUGurokinase
daily short infusions, i. e. i. v. application of 1.000.000 I.E. urokinase over 30 min. for at least 10 and up to 21 days during the 30 days after randomization
Sponsors
GWT-TUD GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age 18 years or older * angiopathic or angioneuropathic critical limb ischemia (at least Wagner-Armstrong stadium II) * participation in the August-1 Register * revascularization not possible or residual ischemia after revascularization * persisting ulcerations despite antibiosis, adjustment of blood glucose levels and debridement * expected further hospitalization for at least 3 weeks (pressure relief and antibiosis) * fibrinogen \>= 4g/l * signed informed consent
Exclusion criteria
* life expectancy \< 1 year * prior major amputation * planned major amputation * prior therapy of the current episode of diabetic foot syndrome with urokinase (except in cases of revascularization when the duration between the intervention and randomization must not exceed 7 days) * mechanical heart valve substitute * cerebral event with CT-detectable changes in the last 3 months * non-remediated proliferation retinopathy * uncontrolled hypertension (systolic \>180 mmg, diastolic \>100 mmHg) * hemorrhagic diathesis (spontaneous quick \< 50%, spontaneous PTT \> 40 s, thrombocytes \< 100 Gpt/l) * gastrointestinal bleeding or ulcers in the last 4 weeks * prior reverse bypass operation * contraindications against therapy with urokinase acc. to the SMPc * concurrent participation in another clinical trial * insufficient compliance * pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Duration of survival without major amputation in urokinase group compared to group with standard therapy | within the FU of 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| minor amputation | 12 months after randomization | — |
| Number of necessary revisions in case of minor amputation | 12 months after randomization | — |
| complete healing of targeted lesion | within the FU of 12 months | — |
| new lesions on previously affected leg | within the FU of 12 months | — |
| efficacy in dialysis patients | within the FU of 12 months | — |
| duration of hospital stay | from baseline examination until first release (expected average of 2 weeks in general) | — |
| total mortality | 12 months after randomization | — |
| Necessity for parenteral therapy with vasoactive substances | from baseline to end of 12 months FU | During the follow-up it will be documented wether the administration of parenterally applied vasoactive substances or thrombocyte aggregation inhibitors was necessary. |
| cardiovascular events | from baseline to end of 12 months FU | Any major cardiovascular events during the follow-up period. Duration, severity, outcome and causal relationship with urokinase therapy will be documented. |
| incidence and type of bleeding events | from randomization until day 33 | — |
| incidence and type of other adverse events | from baseline to end of 12 months FU | — |
| new lesions on the contralateral leg | within the FU of 12 months | — |
| re-hospitalization after dismissal following end of therapy with urokinase | within the FU of 12 months | — |
Countries
Germany
Outcome results
None listed