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

Diabetic Foot Clinical Trial

— August2  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01638585
• Other study ID #: August 2
• Secondary ID: 2010-023426-20
• Status: Terminated
• Phase: Phase 3
• First received: May 14, 2012
• Last updated: April 4, 2014
• Start date: June 2011
• Est. completion date: November 2012

Study information

• Verified date: April 2014
• Source: GWT-TUD GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Limb Ischemia
• Diabetic Foot
• Ischemia

Intervention

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

Locations

Country	Name	City	State
Germany	Diabetes Klinik	Bad Mergentheim
Germany	Ev. KH Königin Elisabeth Herzberge	Berlin
Germany	Martin-Luther-Krankenhaus	Berlin
Germany	Vivantes Klinikum im Friedrichshain	Berlin
Germany	Klinikum Bielefeld gGmbH	Bielefeld
Germany	Stiftungsklinikum Mittelrhein	Boppard
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Klinikum Dortmund gGmbH	Dortmund
Germany	Krankenhaus Dresden-Friedrichstadt	Dresden
Germany	Städtisches Krankenhaus DD-Neustadt	Dresden
Germany	Uniklinikum "Carl Gustav Carus" der TU Dresden	Dresden
Germany	Weißeritztal Kliniken GmbH	Freital
Germany	Asklepios Westklinikum	Hamburg
Germany	Universitätsklinikum Leipzig AöR	Leipzig
Germany	HELIOS Krankenhaus	Leisnig
Germany	Klinikum Westfalen/Klinikum am Park	Lünen
Germany	Klinikum Stuttgart, Bürgerhospital	Stuttgart
Germany	KH der Barmherzigen Brüder	Trier

Sponsors (1)

Lead Sponsor	Collaborator
GWT-TUD GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of survival without major amputation in urokinase group compared to group with standard therapy		within the FU of 12 months	No
Secondary	total mortality		12 months after randomization	No
Secondary	minor amputation		12 months after randomization	No
Secondary	Number of necessary revisions in case of minor amputation		12 months after randomization	No
Secondary	complete healing of targeted lesion		within the FU of 12 months	No
Secondary	new lesions on previously affected leg		within the FU of 12 months	No
Secondary	efficacy in dialysis patients		within the FU of 12 months	No
Secondary	duration of hospital stay		from baseline examination until first release (expected average of 2 weeks in general)	No
Secondary	re-hospitalization after dismissal following end of therapy with urokinase		within the FU of 12 months	No
Secondary	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	No
Secondary	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	No
Secondary	incidence and type of bleeding events		from randomization until day 33	Yes
Secondary	incidence and type of other adverse events		from baseline to end of 12 months FU	Yes
Secondary	new lesions on the contralateral leg		within the FU of 12 months	No