The Therapeutical Role of Continuous Intra-femoral Artery Infusion of Urokinase on Diabetic Foot Ulcers
Condition: Diabetic Foot Ulcer
MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer
Study type: Interventional
Phase: Phase 2

Summary: 
      -  Diabetic foot ulcers (DFU) are one of the chronic consequences of diabetes which
           constitute the most important cause of non-traumatic amputation of the inferior limbs.
           Patients with diabetes are 22 times more likely to have foot ulceration or gangrene than
           nondiabetics，while foot ulceration precedes 85% of lower-extremity amputation.

        -  Three factors combine to promote tissue necrosis in diabetic feet: ischemia, neuropathy
           and trauma. Among them, ischemia peripheral arterial disease may play the important
           roles in the development of DFU. Moreover, diffuse vascular disease is the main
           characteristics, and thus it becomes difficult for treatment by using arterial bypass or
           balloon angioplasty. Therefore, we hypothesized that continuous arterial thrombolysis
           may be an effective therapy in diabetic foot. The purpose of this study is to
           investigate the effectiveness and safety of continuous intra-femoral artery injection of
           urokinase by micro-artery-pump in diabetic ulcers.
    

Detailed description: 
      -  We select 200 diabetic patients with Wagner grade 1 ~ 3 foot ulcers. They are divided
           into two groups randomly: thrombolysis group and control group, 100 cases in each group.

        -  After diabetic dietary advice, all patients receive insulin therapy to control blood
           glucose within a range of 5 - 10 mmol/L. Then the patients receive conventional care for
           their ulcers. To remove extensive callus and necrotic tissue, wound debridement was
           performed. Broad spectrum antibiotics are prescribed if ulcers show clinical signs of
           infection. Adjustments to the treatment are performed when indicated on the basis of
           microbiologic cultures and sensitivity testing.

        -  The conventional group patients receive an intravenous injection of prostaglandin E1 (20
           ug per day)until the healing of ulcers or discharged from hospital. In the continuous
           intra-femoral thrombolysis group, first of all, a ultrasound Doppler examination of
           vessels including artery and venous of lower limbs were performed. To avoid pulmonary
           infarction, a filtrator is placed in the inferior vena cava before the thrombolysis
           process if ultrasound results show venous thrombosis. Then insert a percutaneous artery
           canal from femoral artery in another lower limb into the distal of popliteal artery as
           far as possible. After finishing this process, the outside part of this artery canal is
           fixed at thigh, and the patients must keep in supine position in the bed.Firstly,20 0000
           ~ 40 0000 units urokinase is injected via the catheter to diseased foot. Then,
           continuous infusion urokinase via femoral artery by an artery pump (100 ml 0.9% sodium
           chloride + 100 0000 unit urokinase at a rate of 4 ml per one hour) for 7 - 10 days.
           Finally, patients receive an intravenous injection of prostaglandin E1 (20 ug per
           day)until the healing of ulcers or discharged from hospital.

        -  The healing rate of foot ulcers, the time of ulcers, neuropathy symptoms, the period of
           hospitalization are compared between the two groups during hospitalization.

        -  The recurrence rate of foot ulcers, cardiovascular events, death from all causes are
           compared between two groups at 1, 4, 8 years during follow up.
    

Intervention name(s): continuous intra-femoral thrombolysis group; Conventional therapy group
Intervention type(s): Drug; Drug
Intervention description(s): Firstly, 20 0000 u urokinase is injected to the diseased foot via catheter. Then, continuous injection of urokinase via femoral artery by a artery mini-pump (100 ml 0.9% sodium chloride + 100 0000 unit urokinase at a rate of 4 ml per hour) is taken for 7 - 9 days.; All patients receive an intravenous injection of prostaglandin E1 20 ug per day during hospitalization period.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: diabetic foot ulcer; artery mini-pump; continuous infusion of urokinase; femoral artery