Safety and Efficacy Study of Urokinase for the Treatment of Diabetic Foot Syndrome and Critical Limb Ischemia (August2)
Primary Purpose
Diabetic Foot, Critical Limb Ischemia
Status
Terminated
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
urokinase
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Foot
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
Sites / Locations
- Diabetes Klinik
- Vivantes Klinikum im Friedrichshain
- Ev. KH Königin Elisabeth Herzberge
- Martin-Luther-Krankenhaus
- Klinikum Bielefeld gGmbH
- Stiftungsklinikum Mittelrhein
- Klinikum Chemnitz gGmbH
- Klinikum Dortmund gGmbH
- Städtisches Krankenhaus DD-Neustadt
- Krankenhaus Dresden-Friedrichstadt
- Uniklinikum "Carl Gustav Carus" der TU Dresden
- Weißeritztal Kliniken GmbH
- Asklepios Westklinikum
- Universitätsklinikum Leipzig AöR
- HELIOS Krankenhaus
- Klinikum Westfalen/Klinikum am Park
- Klinikum Stuttgart, Bürgerhospital
- KH der Barmherzigen Brüder
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Active Comparator
Arm Label
standard therapy
urokinase
Arm Description
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.
patients receiving urokinase short infusions in addition to standard therapy
Outcomes
Primary Outcome Measures
Duration of survival without major amputation in urokinase group compared to group with standard therapy
Secondary Outcome Measures
total mortality
minor amputation
Number of necessary revisions in case of minor amputation
complete healing of targeted lesion
new lesions on previously affected leg
efficacy in dialysis patients
duration of hospital stay
re-hospitalization after dismissal following end of therapy with urokinase
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.
cardiovascular events
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
incidence and type of other adverse events
new lesions on the contralateral leg
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01638585
Brief Title
Safety and Efficacy Study of Urokinase for the Treatment of Diabetic Foot Syndrome and Critical Limb Ischemia
Acronym
August2
Official Title
Patients With Diabetic Foot Syndrome and Critical Limb Ischemia - a Randomized Clinical Trial With Urokinase
Study Type
Interventional
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Terminated
Why Stopped
recruition number was not reached
Study Start Date
June 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GWT-TUD GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Foot, Critical Limb Ischemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
standard therapy
Arm Type
No Intervention
Arm Description
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.
Arm Title
urokinase
Arm Type
Active Comparator
Arm Description
patients receiving urokinase short infusions in addition to standard therapy
Intervention Type
Drug
Intervention Name(s)
urokinase
Other Intervention Name(s)
Urokinase HS medac
Intervention Description
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
Primary Outcome Measure Information:
Title
Duration of survival without major amputation in urokinase group compared to group with standard therapy
Time Frame
within the FU of 12 months
Secondary Outcome Measure Information:
Title
total mortality
Time Frame
12 months after randomization
Title
minor amputation
Time Frame
12 months after randomization
Title
Number of necessary revisions in case of minor amputation
Time Frame
12 months after randomization
Title
complete healing of targeted lesion
Time Frame
within the FU of 12 months
Title
new lesions on previously affected leg
Time Frame
within the FU of 12 months
Title
efficacy in dialysis patients
Time Frame
within the FU of 12 months
Title
duration of hospital stay
Time Frame
from baseline examination until first release (expected average of 2 weeks in general)
Title
re-hospitalization after dismissal following end of therapy with urokinase
Time Frame
within the FU of 12 months
Title
Necessity for parenteral therapy with vasoactive substances
Description
During the follow-up it will be documented wether the administration of parenterally applied vasoactive substances or thrombocyte aggregation inhibitors was necessary.
Time Frame
from baseline to end of 12 months FU
Title
cardiovascular events
Description
Any major cardiovascular events during the follow-up period. Duration, severity, outcome and causal relationship with urokinase therapy will be documented.
Time Frame
from baseline to end of 12 months FU
Title
incidence and type of bleeding events
Time Frame
from randomization until day 33
Title
incidence and type of other adverse events
Time Frame
from baseline to end of 12 months FU
Title
new lesions on the contralateral leg
Time Frame
within the FU of 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
S. Schellong, Prof.Dr.med.
Organizational Affiliation
Städt. KH Dresden-Friedrichstadt
Official's Role
Principal Investigator
Facility Information:
Facility Name
Diabetes Klinik
City
Bad Mergentheim
ZIP/Postal Code
97980
Country
Germany
Facility Name
Vivantes Klinikum im Friedrichshain
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
Ev. KH Königin Elisabeth Herzberge
City
Berlin
ZIP/Postal Code
10365
Country
Germany
Facility Name
Martin-Luther-Krankenhaus
City
Berlin
ZIP/Postal Code
14193
Country
Germany
Facility Name
Klinikum Bielefeld gGmbH
City
Bielefeld
ZIP/Postal Code
33602
Country
Germany
Facility Name
Stiftungsklinikum Mittelrhein
City
Boppard
ZIP/Postal Code
56154
Country
Germany
Facility Name
Klinikum Chemnitz gGmbH
City
Chemnitz
ZIP/Postal Code
09113
Country
Germany
Facility Name
Klinikum Dortmund gGmbH
City
Dortmund
ZIP/Postal Code
44145
Country
Germany
Facility Name
Städtisches Krankenhaus DD-Neustadt
City
Dresden
ZIP/Postal Code
01129
Country
Germany
Facility Name
Krankenhaus Dresden-Friedrichstadt
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Uniklinikum "Carl Gustav Carus" der TU Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Weißeritztal Kliniken GmbH
City
Freital
ZIP/Postal Code
01705
Country
Germany
Facility Name
Asklepios Westklinikum
City
Hamburg
ZIP/Postal Code
22559
Country
Germany
Facility Name
Universitätsklinikum Leipzig AöR
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
HELIOS Krankenhaus
City
Leisnig
ZIP/Postal Code
04703
Country
Germany
Facility Name
Klinikum Westfalen/Klinikum am Park
City
Lünen
ZIP/Postal Code
44536
Country
Germany
Facility Name
Klinikum Stuttgart, Bürgerhospital
City
Stuttgart
ZIP/Postal Code
70191
Country
Germany
Facility Name
KH der Barmherzigen Brüder
City
Trier
ZIP/Postal Code
54292
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study of Urokinase for the Treatment of Diabetic Foot Syndrome and Critical Limb Ischemia
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