A phase 2 randomized, double-blind, placebo-controlled study of the safety and efficacy of talactoferrin in patients with severe sepsis.

OBJECTIVES: Lactoferrin is a glycoprotein with anti-infective and anti-inflammatory properties found in secretions and immune cells. Talactoferrin alfa, a recombinant form of human lactoferrin, has similar properties and plays an important role in maintaining the gastrointestinal mucosal barrier integrity. In experimental animal models, administration of talactoferrin reduces translocation of bacteria from the gut into the systemic circulation and mortality from sepsis. Our objective was to determine if talactoferrin could reduce 28-day all-cause mortality in patients with severe sepsis and to assess its safety. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial. SETTING: Adult ICUs and emergency departments in the United States. PATIENTS: One hundred ninety-four adults within 24 hrs of the onset of severe sepsis. INTERVENTIONS: Enterally administered talactoferrin 1.5g or placebo every 8 hrs for up to 28 days or until discharge from the ICU. MEASUREMENTS AND MAIN RESULTS: Modified intention-to-treat analysis was used to assess the primary (28-day all-cause mortality) and secondary endpoints. The all-cause mortality at 28 days was 26.9% in the placebo group and 14.4% in the talactoferrin group (two-sided p = 0.052), representing a 12.5% absolute and a 46.5% relative reduction in mortality, meeting the protocol-specified primary endpoint. Reduction in all cause mortality was sustained at 6 months (p = 0.039). These reductions in mortality were observed across a wide spectrum of subgroups. The drug was well tolerated with a safety profile similar to that of placebo. CONCLUSIONS: Enteral administration of talactoferrin reduced 28-day all-cause mortality in patients with severe sepsis. This reduction in mortality was sustained at 6 months. Talactoferrin was very well tolerated.

Recanalization of chronic total peripheral arterial occlusions using optical coherent reflectometry with guided radiofrequency energy: a single center experience.

BACKGROUND: A forward-looking, fiberoptic guided device (Safe-Cross System, Intraluminal Therapeutics, Carlsbad, CA) has been used with guided radiofrequency energy to open chronic total occlusions (CTOs). This report describes the use of optical coherent reflectometry (OCR) system to assess safety and efficacy of opening CTOs in native peripheral arteries in the lower extremities: iliac, femoral, and popliteal. METHODS: 18 CTOs in native peripheral arteries in 17 patients were treated with OCR after failed attempts with conventional wires (minimum 10 min of fluoroscopic time). When the CTO was crossed, routine angioplasty with or without stent was performed. Efficacy was defined as achievement of distal lumen position. Safety was defined as device success without perforation, dissection (> or =Grade C), or distal embolization. The mean patient age was 72 years with 8 females and 10 males. Lesion characteristics included a mean vessel diameter of 5.8 mm and a mean lesion length of 22.4 cm. Ankle-brachial indices was < or =0.8 in all patients. RESULTS: The OCR system was successful in crossing 100% of the CTOs in patients that failed conventional wire crossing, whereas clinical success occurred in 94% of these patients. Complications consisted of a single dissection > or =Grade C. No perforations or distal embolization occurred. CONCLUSIONS: The Safe-Cross OCR System is both efficacious and safe in the treatment of CTOs that failed crossing with conventional wires and indirect visualization of the intraluminal position by using OCR technology appears to minimize vessel trauma, dissection, perforation, and distal embolization.

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study.

BACKGROUND: Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models. METHODS: A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size). RESULTS: The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities. CONCLUSIONS: Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.

Devices for chronic occlusion.

Interventional cardiology has advanced into domains once believed to be beyond the reach of percutaneous procedures. As technologic advances continue to push the limits of the interventionalist's capabilities, several areas still exert considerable resistance to this forward momentum. These technically difficult frontiers include bifurcated lesions, small-vessel disease, multivessel disease, diffuse disease, and chronic total occlusions.