Topically applied recombinant tissue plasminogen activator for the treatment of venous ulcers. Preliminary report.
BACKGROUND
Increasing evidence suggests that fibrin deposition is an important pathogenic component of venous ulceration and that fibrin removal could accelerate ulcer healing.


OBJECTIVE
We sought to determine whether topical application of recombinant tissue plasminogen activator (tPA) compounded in 1% hyaluronate acid (HA) can be used safely in venous ulcers and whether it can accelerate healing.


METHODS
Twelve patients were randomized in a double-blind fashion in three sequential groups of four subjects each, so as to receive daily topical application of either placebo (HA alone, one patient) or tPA/HA (three patients) at escalating doses of 0.25, 0.5, and 1.0 mg/ml of tPA for 4 weeks.


RESULTS
No safety problems occurred, and we found a close direct correlation between mean ulcer reepithelialization, fibrin removal, and the dose of topically applied tPA (r = 0.991).


CONCLUSIONS
In this first study to examine its usefulness, topically applied tPA appears to be a safe and promising agent for treating venous ulcers.
Falanga
V
V
Department of Dermatology and Cutaneous Surgery, University of Miami, University of Miami School of Medicine, FL 33101, USA.
Carson
P
P
Greenberg
A
A
Hasan
A
A
Nichols
E
E
McPherson
J
J
D000279:Administration, Cutaneous; D004311:Double-Blind Method; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005240:Feasibility Studies; D005337:Fibrin / Q000037:antagonists & inhibitors; D005500:Follow-Up Studies; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage; D014677:Pharmaceutical Vehicles; D010865:Pilot Projects; D010919:Placebos; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012449:Safety; D012867:Skin / Q000187:drug effects / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014647:Varicose Ulcer / Q000188:drug therapy* / Q000473:pathology; D014945:Wound Healing
D014677:Pharmaceutical Vehicles; D010919:Placebos; D011994:Recombinant Proteins; D005337:Fibrin; D006820:Hyaluronic Acid; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator