Urokinase Therapy in Patients With Diabetic Foot Syndrome

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether the additional therapy with low dose urokinase is more effective than only a conventional standard therapy concerning ulcer-healing, rate of major amputation and survival.

Detailed Description
-----------------
Patients with diabetic foot ulceration and critical limb ischemia have a high risk of major amputation, especially if limbs can not be revascularized. Urokinase is effective in critical limb ischemia by lowering fibrinogen and might improve outcomes. The effect and safety of urokinase treatment was investigated in a phase II clinical trial. Based on the results this trial was planned to investigate the effect and safety of an additional therapy with urokinase versus a single conventional therapy.

Official Title
-----------------
Low Dose Urokinase Therapy in Patients With Diabetic Foot Syndrome and Critical Limb Ischemia Versus Conventional Standard Therapy

Conditions
-----------------
Diabetic Foot, Arterial Occlusive Disease, Ischemia

Intervention / Treatment
-----------------
* Procedure: standard therapy
* Drug: Urokinase


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diabetic patients with angiopathic or angioneuropathic diabetic foot syndrome and criticial limb ischemia No surgical or interventional treatment option No healing tendency of ulcerations despite of antibiosis and wound debridement after two-week treatment Fibrinogen > 4.0 g/l No previous major amputation Exclusion Criteria: Prior treatment of the current ulceration with urokinase Need for dialysis and/or creatinine-clearance < 20ml/min INR > 1,5 at screening Any kind of cerebral event within 3 months prior inclusion Proliferative retinopathy Uncontrolled hypertension Hemorraghic diathesis Gastrointestinal bleeding Pregnancy No compliance and/or participation in another trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: A: Standard therapy<br> | Procedure: standard therapy<br>* wound debridement, moist wound dressing<br>|
| Experimental: B: Urokinase<br> | Drug: Urokinase<br>* Daily infusion up to 21 applications, dose dependent on fibrinogen level: > 2,5g/l 1 000 000 IU, < 2,5g/l 500 000 IU<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major amputation free survival |  | Within twelve months after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total survival, major amputation rate, rate of complete ulcer healing, rate of adverse events |  | Within twelve month after randomisation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, urokinase, ulcer healing, major amputation, survival