Diabetic Foot Ulcers
Encelle, Inc, Raleigh, NC, has been awarded a 3-year, $1.7 million grant from the National Institutes of Health (NIH) to accelerate development of E-Matrix for treatment of diabetic foot wounds. E-Matrix is an injectable biopolymer shown in animal studies to promote healing of skin wounds.
Encelle has also initiated a controlled pilot clinical study of E-Matrix for treatment of diabetic foot ulcers at 10 US sites. This study will assess E-Matrix treatment versus standard wound care among 60 patients with chronic ulcers. Smith & Nephew, Largo, FL, which is providing funds for the study, has a worldwide license for E-Matrix in the treatment of cutaneous wounds.
Topical recombinant human lactoferrin (rhLF) gel (Agennix, Inc, Houston, TX) consistently increased the rate and incidence of wound closure relative to placebo and to the approved drug therapy (rh-PDGF-BB, becaplermin) in mice with full-thickness wounds. Both healthy mice and diabetic mice with impaired healing were used in the trial.
RhLF has been used in humans as well and it appears to be safe and well tolerated: More than 300 people have used rhLF, topically and orally, without serious drug-related adverse events. A blinded, multicenter Phase I/II clinical trial will evaluate the safety and efficacy of topical rhLF in patients with diabetic foot ulcers. After the initial dose escalation phase, patients will be randomized between placebo and 2 doses of rhLF. Results from the efficacy phase of the trial are expected in early 2004.
Burn Wounds
The effectiveness of Vacuum Assisted Closure (V.A.C.) Therapy (Kinetic Concepts, Inc, San Antonio, TX) for use with partial-thickness burns was discussed at the American Burn Association Annual Meeting by David Heimbach, MD, of the University of Washington's Harborview Burn Center. Harborview is a participant in multicenter clinical trials exploring the use of V.A.C. Therapy in partial-thickness hand burns. The Food and Drug Administration granted clearance of V.A.C. Therapy for use with partial-thickness burns in January 2003.
Dr Heimbach said the hand burn study compares V.A.C. Therapy with standard topical antibiotic treatments. The study design evaluates randomly selected symmetrical and bilateral hand burns. One hand is treated for 48 hours with V.A.C. Therapy at 125 mm Hg controlled subatmospheric pressure, followed by traditional silver sulfadiazene protocols. The control hand is treated using only the silver sulfadiazene protocols from the outset. The hand treated with V.A.C. Therapy is placed in a specially configured V.A.C. dressing.
According to KCI's medical research team, V.A.C. Therapy enhances partial-thickness burn treatments because it helps remove infectious materials, may reduce the risk of infection due to its closed system, helps promote flap and graft survival, and collects and quantifies fluid output.
Skin Infections
InterMune, Inc, Brisbane, CA, announced positive top-line results of a confirmatory pivotal Phase III clinical trial of oritavancin, the company's intravenous investigational antibiotic, for the treatment of complicated skin/skin-structure infections (cSSSI) caused by Gram-positive bacteria. Oritavancin, a second-generation glycopeptide antibiotic, has bactericidal activity against a broad spectrum of Gram-positive bacteria, including those resistant to vancomycin.
The double-blind, active comparator, noninferiority Phase III study was designed to assess the clinical and bacteriologic efficacy of intravenous therapy with oritavancin alone versus the traditional approach of intravenous therapy with vancomycin followed by oral therapy with cephalexin. The study enrolled 1267 patients with cSSSI caused by Gram-positive pathogens at 103 sites in 22 countries. Patients were randomized to receive oritavancin once daily for 3 to 7 days followed by oral placebo, or vancomycin for 3 to 7 days followed by oral cephalexin, for a total course of 10 to 14 days in both treatment arms.
The primary efficacy end point of clinical cure of infection, as well as the secondary measure of bacteriologic eradication, was met, demonstrating oritavancin was as effective as the comparator agents despite being administered for an average of only 5.3 days, compared with 10.9 days for the vancomycin/cephalexin group. Furthermore, oritavancin showed a significantly improved safety profile, with a 19.2% relative reduction in the overall incidence of adverse events versus vancomycin/cephalexin (P <.001).
Not yet approved by the Food and Drug Administration, oritavancin has been well tolerated in clinical trials.
Diabetic Neuropathy
A new analysis of data from the Glycemic Optimization with Algorithms and Labs At Po1int of Care (GOAL A1C) study, presented at the American Diabetes Association (ADA) 63rd Scientific Sessions in June suggests both primary care providers and endocrinology specialists can miss a diagnosis of peripheral neuropathy in their patients with diabetes.
The ADA presentation summarized data on 7378 patients with type 2 diabetes (target enrollment for the ongoing study is 14,000 patients). Most patients (88%) were treated in a primary care provider's office; the remaining 12% were treated at endocrinology clinics. Patients were screened for the presence of significant neuropathy using a monofilament and evaluated for clinical symptoms.
More than half of the patients in the study (63%) did not have neuropathy. Testing showed that 30% had nonsevere neuropathy and 7% had severe neuropathy. In most cases (92.4%), the treating physician had correctly identified that the patient did not have neuropathy. But physicians did not do as well at identifying patients who did have neuropathy: They missed the diagnosis in nearly two thirds (62.4%) of patients who were positive for neuropathy.
Patients with neuropathy differed significantly from those without neuropathy. They were older, predominantly male, had a longer duration of diabetes, had slightly higher A1C values, had more foot ulcers and more pins and needles in the feet, and wore more custom footwear.
According to the authors, these data demonstrate that neuropathy is a commonly underdiagnosed complication of diabetes in primary care practice and underscore the importance of routine testing for presence of neuropathy on a regular basis.
The GOAL A1C study is being funded by Aventis, Bridgewater, NJ.