No abstract

Background. Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, Rifamycin SV MMX ® (RIF-MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a unique rifamycin drug. Methods. This was a randomized, double-blind, phase 3 study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A total of 264 patients received RIF-MMX (2 × 200 mg twice daily for 3 days, n = 199) or placebo (n = 65) in a 3 : 1 ratio. The primary endpoint was the length of time between the administration of first dose of study drug and passage of the last unformed stool (TLUS; after which clinical cure was declared). Other endpoints included eradication of pathogens from the stools, pathogen minimum inhibitory concentration (MIC), and adverse events (AEs). Results. TLUS was significantly shorter in the RIF-MMX group (median: 46.0 hours) compared with placebo (median: 68.0 hours; p = 0.0008) and a larger percentage of RIF-MMX treated patients (81.4%) achieved clinical cure compared with placebo patients (56.9%). TLUS was significantly shorter in the subgroups of patients with enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli infections (p = 0.0035) with nonsignificant activity against invasive bacteria (p = 0.3804). Overall pathogen eradication rates were numerically higher in the RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not reach significance (p = 0.0836). In vitro resistance to rifamycin SV was observed in some bacteria remaining after treatment of patients with RIF-MMX but was not associated with lower efficacy in them. AEs appeared to be more frequent with placebo (38.5%) than with RIF-MMX (29.6%). Conclusions. RIF-MMX shortened the duration of TD in patients with a broad range of pathogens and was well tolerated. The unique pharmacokinetic properties of the drug offer evidence that TD pathogens work at the level of the colon.

No abstract

Transurethral resection of the prostate (TURF) and open adenectomy are regarded the golden standard in the management of patients with symptomatic benign prostatic hyperplasia (BPH). Various alternative treatment forms (microwaves, laser, radiofrequency, focused ultrasound) have been introduced recently. They all aim at reduction of morbidity related to TURP keeping a comparable efficacy at the same time. Since December 1992, 50 patients with BPH have been treated by high intensity focused ultrasound (HIFU-P) at our department. Six weeks following HIFU-P mean Qmax improved from 5.7ml/s to 11.6ml/s. Post voiding residual volume (RV) dropped from 215ml to 100ml, the International Prostate Symptom Score (IPSS) from 19.8 to 9.9. Both, IPSS and RV further improved during the following weeks. Follow-up data one year after treatment demonstrate that results remained stable in the majority of patients. Urinary tract infections were observed in 3 patients, macrohematospermia in all and macro hematuria (caused by the suprapubic catheter) requiring blood transfusion in 1 patient.

Background Calcific uremic arteriolopathy (calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterised by poorly healing or nonhealing wounds, and is associated with mortality, substantial morbidity related to infection, and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain, and improvement in wound-related quality of life. Those results informed the design of the CALCIPHYX trial, an ongoing, randomised, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis. Methods In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomised 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in BWAT-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related quality of life, qualitative changes in wounds, wound size, analgesic use, and safety. Conclusions This randomised, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.