Clinical trial NCT01638585: Safety and Efficacy Study of Urokinase for the Treatment of Diabetic Foot Syndrome and Critical Limb Ischemia
Official title: Patients With Diabetic Foot Syndrome and Critical Limb Ischemia - a Randomized Clinical Trial With Urokinase
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetic Foot
Critical Limb Ischemia
Lead sponsor: GWT-TUD GmbH
Sponsor class: OTHER
First posted: 2012-07-11
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of survival without major amputation in urokinase group compared to group with standard therapy
timeFrame: within the FU of 12 months
Secondary outcomes:
measure: total mortality
timeFrame: 12 months after randomization
measure: minor amputation
timeFrame: 12 months after randomization
measure: Number of necessary revisions in case of minor amputation
timeFrame: 12 months after randomization
measure: complete healing of targeted lesion
timeFrame: within the FU of 12 months
measure: new lesions on previously affected leg
timeFrame: within the FU of 12 months
measure: efficacy in dialysis patients
timeFrame: within the FU of 12 months
measure: duration of hospital stay
timeFrame: from baseline examination until first release (expected average of 2 weeks in general)
measure: re-hospitalization after dismissal following end of therapy with urokinase
timeFrame: within the FU of 12 months
measure: Necessity for parenteral therapy with vasoactive substances
timeFrame: from baseline to end of 12 months FU
measure: cardiovascular events
timeFrame: from baseline to end of 12 months FU
measure: incidence and type of bleeding events
timeFrame: from randomization until day 33
measure: incidence and type of other adverse events
timeFrame: from baseline to end of 12 months FU
measure: new lesions on the contralateral leg
timeFrame: within the FU of 12 months
Other outcomes:
Locations:
city: Bad Mergentheim
country: Germany
facility: Diabetes Klinik
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Berlin
country: Germany
facility: Ev. KH Königin Elisabeth Herzberge
city: Berlin
country: Germany
facility: Martin-Luther-Krankenhaus
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld gGmbH
city: Boppard
country: Germany
facility: Stiftungsklinikum Mittelrhein
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Dresden
country: Germany
facility: Städtisches Krankenhaus DD-Neustadt
city: Dresden
country: Germany
facility: Krankenhaus Dresden-Friedrichstadt
city: Dresden
country: Germany
facility: Uniklinikum "Carl Gustav Carus" der TU Dresden
city: Freital
country: Germany
facility: Weißeritztal Kliniken GmbH
city: Hamburg
country: Germany
facility: Asklepios Westklinikum
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR
city: Leisnig
country: Germany
facility: HELIOS Krankenhaus
city: Lünen
country: Germany
facility: Klinikum Westfalen/Klinikum am Park
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart, Bürgerhospital
city: Trier
country: Germany
facility: KH der Barmherzigen Brüder
Study officials:
affiliation: Städt. KH Dresden-Friedrichstadt
name: S. Schellong, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References: