Safety and Efficacy Study of Urokinase for the Treatment of Diabetic Foot Syndrome and Critical Limb Ischemia

Phase 3

Terminated

• Conditions: Critical Limb Ischemia; Diabetic Foot
• Interventions: Drug: urokinase

• Registration Number: NCT01638585
• Lead Sponsor: GWT-TUD GmbH

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.

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2012-05-14
• Study First Submitted QC: 2012-07-09
• Study First Posted: 2012-07-11
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-04
• Last Update Posted: 2014-04-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
urokinase	urokinase	patients receiving urokinase short infusions in addition to standard therapy

Primary Outcome Measures

Name	Time	Method
Duration of survival without major amputation in urokinase group compared to group with standard therapy	within the FU of 12 months

Secondary Outcome Measures

Name	Time	Method
total mortality	12 months after randomization
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)
re-hospitalization after dismissal following end of therapy with urokinase	within the FU of 12 months
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

Trial Locations

Locations (18)

Städtisches Krankenhaus DD-Neustadt; 🇩🇪 Dresden, Germany

Klinikum Westfalen/Klinikum am Park; 🇩🇪 Lünen, Germany

Vivantes Klinikum im Friedrichshain; 🇩🇪 Berlin, Germany

Martin-Luther-Krankenhaus; 🇩🇪 Berlin, Germany

Klinikum Bielefeld gGmbH; 🇩🇪 Bielefeld, Germany

Diabetes Klinik; 🇩🇪 Bad Mergentheim, Germany

Stiftungsklinikum Mittelrhein; 🇩🇪 Boppard, Germany

Klinikum Chemnitz gGmbH; 🇩🇪 Chemnitz, Germany

Ev. KH Königin Elisabeth Herzberge; 🇩🇪 Berlin, Germany

Klinikum Dortmund gGmbH; 🇩🇪 Dortmund, Germany

Asklepios Westklinikum; 🇩🇪 Hamburg, Germany

HELIOS Krankenhaus; 🇩🇪 Leisnig, Germany

Krankenhaus Dresden-Friedrichstadt; 🇩🇪 Dresden, Germany

Uniklinikum "Carl Gustav Carus" der TU Dresden; 🇩🇪 Dresden, Germany

Universitätsklinikum Leipzig AöR; 🇩🇪 Leipzig, Germany

KH der Barmherzigen Brüder; 🇩🇪 Trier, Germany

Weißeritztal Kliniken GmbH; 🇩🇪 Freital, Germany

Klinikum Stuttgart, Bürgerhospital; 🇩🇪 Stuttgart, Germany