Safety and Efficacy Study of Urokinase for the Treatment of Diabetic Foot Syndrome and Critical Limb Ischemia (August2)

Patients With Diabetic Foot Syndrome and Critical Limb Ischemia - a Randomized Clinical Trial With Urokinase

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.

Study Overview

• Status: Terminated
• Conditions: Diabetic Foot; Critical Limb Ischemia
• Intervention / Treatment: Drug: urokinase

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bad Mergentheim, Germany, 97980
    • Diabetes Klinik
  • Berlin, Germany, 10249
    • Vivantes Klinikum Im Friedrichshain
  • Berlin, Germany, 14193
    • Martin-Luther-Krankenhaus
  • Berlin, Germany, 10365
    • Ev. KH Königin Elisabeth Herzberge
  • Bielefeld, Germany, 33602
    • Klinikum Bielefeld gGmbH
  • Boppard, Germany, 56154
    • Stiftungsklinikum Mittelrhein
  • Chemnitz, Germany, 09113
    • Klinikum Chemnitz gGmbH
  • Dortmund, Germany, 44145
    • Klinikum Dortmund gGmbH
  • Dresden, Germany, 01129
    • Städtisches Krankenhaus DD-Neustadt
  • Dresden, Germany, 01307
    • Krankenhaus Dresden-Friedrichstadt
  • Dresden, Germany, 01307
    • Uniklinikum "Carl Gustav Carus" der TU Dresden
  • Freital, Germany, 01705
    • Weißeritztal Kliniken GmbH
  • Hamburg, Germany, 22559
    • Asklepios Westklinikum
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig AöR
  • Leisnig, Germany, 04703
    • HELIOS Krankenhaus
  • Lünen, Germany, 44536
    • Klinikum Westfalen/Klinikum am Park
  • Stuttgart, Germany, 70191
    • Klinikum Stuttgart, Bürgerhospital
  • Trier, Germany, 54292
    • KH der Barmherzigen Brüder

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: standard therapy; patients receiving standard therapy for diabetic foot syndrome with critical limb ischemia, i. e. structured therapy of lesions with antibiosis, pressure relief and therapy of risk factors according to the relevant guidelines.
Active Comparator: urokinase; patients receiving urokinase short infusions in addition to standard therapy	Drug: urokinase; 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; Other Names: Urokinase HS medac

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	During the follow-up it will be documented wether the administration of parenterally applied vasoactive substances or thrombocyte aggregation inhibitors was necessary.	from baseline to end of 12 months FU
cardiovascular events	Any major cardiovascular events during the follow-up period. Duration, severity, outcome and causal relationship with urokinase therapy will be documented.	from baseline to end of 12 months FU
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

Collaborators and Investigators

• Sponsor: GWT-TUD GmbH
• Investigators: Principal Investigator: S. Schellong, Prof.Dr.med., Städt. KH Dresden-Friedrichstadt

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: May 14, 2012
• First Submitted That Met QC Criteria: July 9, 2012
• First Posted (Estimate): July 11, 2012

Study Record Updates

• Last Update Posted (Estimate): April 7, 2014
• Last Update Submitted That Met QC Criteria: April 4, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Ulcer; Diabetic Foot; Ischemia
• Other Study ID Numbers: August 2; 2010-023426-20 (EudraCT Number)