Effects of Sustained-Release Beraprost in Patients With Primary Glomerular Disease or Nephrosclerosis: CASSIOPEIR Study Results.

TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 µg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 µg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.

Orally active prostacyclin analogue beraprost sodium in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled, phase II dose finding trial.

BACKGROUND: Evidence increasingly points to the importance of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal disease (ESRD). Beraprost sodium (BPS) is an orally active prostacyclin (PGI2) analogue demonstrating prevention of the progression of chronic kidney disease (CKD) in various animal models by maintaining renal blood flow and attenuating renal ischemic condition. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase II trial was designed to determine the recommended dose of the sustained-release form of BPS (TRK-100STP 120 µg/day or 240 µg/day) in Japanese patients with CKD. TRK-100STP was administered to a total of 112 patients. The primary efficacy endpoint was the difference in the slope of the regression line of reciprocal of serum creatinine (1/SCr) over time, obtained by the least-squares method. RESULTS: Regarding the primary endpoint, statistical superiority of TRK-100STP 240 µg over placebo was not confirmed and so a recommended dose was not determined. Compared to placebo, however, the slope of regression line of 1/SCr, elevation of SCr and serum cystatin C during the treatment period revealed greater improvement at 120 µg, at both doses, and at 240 µg, respectively. In terms of safety, both TRK-100STP treatment groups were well tolerated. CONCLUSIONS: Although the study failed to meet the primary endpoint, results indicate that TRK-100STP may potentially prevent the decline in renal function of CKD patients independent of blood pressure or urinary protein levels. TRIAL REGISTRATION: NCT02480751. June 21, 2015.

A multinational phase IIb/III trial of beraprost sodium, an orally active prostacyclin analogue, in patients with primary glomerular disease or nephrosclerosis (CASSIOPEIR trial), rationale and study design.

BACKGROUND: Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-100STP, a sustained release tablet of an orally-active prostacyclin analogue, beraprost sodium, is suggested to suppress worsening of some parameters of renal filtration function, containing in slope of 1/serum creatinine (1/SCr) vs. time in a phase II clinical trial. METHODS/DESIGN: We describe the design of the phase IIb/III trial of TRK-100STP, CASSIOPEIR (CRF Asian Study with Oral PGI2 derivative for Evaluating Improvement of Renal function) conducted in approximately 160 centers in China, Hong Kong, Japan, Malaysia, Republic of Korea, Taiwan, and Thailand. A total of 750 patients (n = 250 per group) with primary glomerular disease or nephrosclerosis were planned to be enrolled. Patients were randomized into one of three treatment groups in a double-bind, placebo-controlled manner: TRK-100STP 60 µg b.i.d.; TRK-100STP 120 µg b.i.d.; or placebo. The treatment period is planned to last 2 to 4 years. The primary efficacy endpoint is the renal composite endpoint including doubling of SCr and ESRD (dialysis induction, renal transplantation, or increase in SCr to ≥ 6.0 mg/dL). DISCUSSION: This trial targeting CKD patients is designed to (a) demonstrate the superiority of TRK-100STP over placebo using renal composite endpoints, (b) determine the recommended clinical dose, and (c) assess the safety of TRK-100STP in this population and setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01090037.

Antibacterial properties of a self-cured acrylic resin composed of a polymer coated with a silver-containing organic composite antibacterial agent.

A novel antibacterial polymer, coated with a silver-containing organic composite antibacterial agent, was dispersed in a self-cured acrylic resin. Residual viable cell count of each oral bacterial and fungal species cultivated on acrylic resin specimens containing the antibacterial polymer was significantly decreased when compared to those cultivated on specimens prepared from untreated polymer. A strong inverse correlation was found between the amount of eluted silver ions and the residual viable cell count of all species grown on the antibacterial polymer: the lower the viable cell count, the higher the amount of eluted silver ions. This clearly indicated the antibacterial activity of silver ions. As the content of organic composite antibacterial agent added to the polymer increased from 0.5% to 1.5% in 0.5% increments, amount of eluted silver ions significantly increased with each 0.5% increment to exert greater antibacterial effect.

In vitro biocompatibility of dextrin: the addition of a low concentration of dextrin in the medium promotes the cell activity of L929 mouse fibroblasts.

To develop a bone substitute with shape-generating properties, we focused our attention on dextrin, which has a low viscosity. After considering methods of evaluation for research and development, we started by using cells that are widely used for safe biological evaluations in the field of dentistry and conducted in vitro evaluations. In this experiment, we variously added concentrations of 0.1, 1.0 and 10 mmol/l of dextrin to a culture medium in order to examine the effects on L929 mouse fibroblasts in vitro. As a result, the proliferative activity of the L929 cells was promoted during the culture period as the concentration of added dextrin became lower, and in particular, the 0.1 and 1 mmol/l addition group showed higher values than those of the control group. From the above results, it was revealed that the addition of a low concentration of dextrin in a medium promotes the cell proliferative activity.

Residual washing detergent in cotton clothes: a factor of winter deterioration of dry skin in atopic dermatitis.

Although it is well known that the skin in patients with atopic dermatitis becomes drier in winter, the mechanisms of winter deterioration of dry skin are not fully understood. Our purpose was to determine whether residual washing detergent in cotton clothes plays a role in the winter deterioration of atopic dry skin. We studied 148 Japanese patients with atopic dermatitis who visited our dermatology clinic during winter months. They wore cotton underwear, which they had washed in cold tap water. We examined the distribution of dry skin on their trunks. We then asked them to stop washing their clothes with common anionic, additive-enriched detergents, and to use a nonionic, additive-reduced detergent for a period of two weeks. Photographs of 2 or 3 representative dry skin sites on the trunk were taken before and after the trial. By comparing the before-after trial photographs, the severity of dry skin at the end of the trial was assessed on a 5-point scale ranging from markedly improved to worsened. Of the 148 patients examined, 115 (78%) had widespread or localized dry skin on the trunk. The dryness of the skin was prominent around the shoulders. Of these 115 patients, 87 (76%) showed marked or moderate improvement of dry skin after the two-weeks of use of the nonionic, additive-reduced washing detergent. No patient showed worsening of the dry skin. These results suggest that residues of common washing detergents in cotton underclothes play an important role in the winter deterioration of dry skin in patients with atopic dermatitis who use cold tap water for washing their clothes.