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

• ClinicalTrials.gov Identifier: NCT01638585
• Recruitment Status: Terminated
• First Posted: July 11, 2012
• Last Update Posted: April 7, 2014
• Sponsor: GWT-TUD GmbH
• Information provided by (Responsible Party): GWT-TUD GmbH

Tracking Information

• First Submitted Date: May 14, 2012
• First Posted Date: July 11, 2012
• Last Update Posted Date: April 7, 2014
• Study Start Date: June 2011
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 9, 2012): Duration of survival without major amputation in urokinase group compared to group with standard therapy [ Time Frame: within the FU of 12 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 9, 2012)

• total mortality [ Time Frame: 12 months after randomization ]
• minor amputation [ Time Frame: 12 months after randomization ]
• Number of necessary revisions in case of minor amputation [ Time Frame: 12 months after randomization ]
• complete healing of targeted lesion [ Time Frame: within the FU of 12 months ]
• new lesions on previously affected leg [ Time Frame: within the FU of 12 months ]
• efficacy in dialysis patients [ Time Frame: within the FU of 12 months ]
• duration of hospital stay [ Time Frame: from baseline examination until first release (expected average of 2 weeks in general) ]
• re-hospitalization after dismissal following end of therapy with urokinase [ Time Frame: within the FU of 12 months ]
• Necessity for parenteral therapy with vasoactive substances [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: from randomization until day 33 ]
• incidence and type of other adverse events [ Time Frame: from baseline to end of 12 months FU ]
• new lesions on the contralateral leg [ Time Frame: within the FU of 12 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Diabetic Foot
• Critical Limb 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

Other Name: Urokinase HS medac

Study Arms

• 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
  Intervention: Drug: urokinase

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 4, 2014): 34
• Original Estimated Enrollment (submitted: July 9, 2012): 211
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01638585
• Other Study ID Numbers: August 2; 2010-023426-20 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: GWT-TUD GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: GWT-TUD GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: S. Schellong, Prof.Dr.med.; Städt. KH Dresden-Friedrichstadt

• PRS Account: GWT-TUD GmbH
• Verification Date: April 2014