Real-time determination of Kt/V can be provided by monitoring ultraviolet absorbance of solutes in spent dialysate. This not only overcomes dependency on errorprone pre-and post-dialysis blood sampling; it circumvents inaccuracies associated with estimating the urea distribution volume and its high measurement frequency tightly reflects the course of the dialysis. Our study compared the ultraviolet-based spKt/V and eKt/V with the commonly used blood-based counterparts. A first study of 16 patients compared ultraviolet Kt/Vs against blood Kt/Vs obtained by using the 'gold standard' of serial blood samples. A second study included 18 patients and compared the ultraviolet and blood values under routine conditions. Both studies showed mean blood-based spKt/V and eKt/V values statistically indistinguishable from their ultraviolet-based counterparts. Hence, on-line monitoring of ultraviolet absorption of spent dialysate is applicable in routine hemodialysis allowing continuous measure of removed solutes from spent dialysate without disturbing the patient or treatment session.

Background Astodrimer Gel contains a novel dendrimer intended to treat and prevent bacterial vaginosis. We assessed the efficacy and safety of Astodrimer Gel for treatment of bacterial vaginosis. Methods 132 women with bacterial vaginosis were randomized 1:1:1:1 to Astodrimer 0.5% (N = 34), 1% (N = 33), or 3% (N = 32) Gel or hydroxyethyl cellulose placebo gel (N = 33) at a dose of 5 g vaginally once daily for 7 days at 6 centers in the United States. The primary endpoint was clinical cure (no bacterial vaginosis vaginal discharge and no more than one of 1) vaginal pH �4.5; 2) �20% clue cells; or 3) positive whiff test) at study days 21-30. Secondary analyses included clinical cure at study days 9-12, patient-reported symptoms, acceptability and adverse events. Results The Astodrimer 1% Gel dose was superior to placebo for the primary and selected secondary efficacy measures in the modified intent-to-treat population. Clinical cure rates at day 9-12 were superior to placebo for the Astodrimer 3%, 1% and 0.5% Gel groups (62.5% [15/ 24; P = .002], 74.1% [20/27; P < .001], and 55.2% [16/29; P = .001], respectively, vs. 22.2% [6/27]). At day 21-30, clinical cure rates were 46.2% (12/26) for the 1% dose vs. 11.5% for placebo (3/26; P = .006). A greater proportion of patients reported absence of vaginal discharge and vaginal odor at day 9-12 and day 21-30 for Astodrimer Gel groups compared with placebo. Adverse events considered potentially treatment-related occurred in only 25% of Astodrimer Gel-treated patients vs. 22% of placebo patients.

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Highlights Recurrent bacterial vaginosis impacts on women and carries a high financial burden. Astodrimer 1% Gel was superior to placebo for prevention of recurrent BV. Astodrimer 1% Gel was well tolerated when used every second day for 16 weeks. Results support the use of Astodrimer 1% Gel for prevention of recurrent BV.

Background: Bacterial vaginosis is highly recurrent after antibiotic treatment, and prevention represents an unmet medical need. Astodrimer 1% Gel contains a novel dendrimer that blocks bacterial attachment and has been shown to effectively treat bacterial vaginosis. Objective: The objective of the study was to confirm the efficacy and safety of Astodrimer 1% Gel to prevent recurrence of bacterial vaginosis. Study Design: 864 women with a current episode of bacterial vaginosis and a history of recurrent bacterial vaginosis were enrolled in the open-label phase of the study to receive oral metronidazole (500 mg twice daily for 7 days) at 77 centers in North America. 586 women successfully treated with metronidazole were randomly assigned 1:1 to Astodrimer 1% Gel or placebo at a dose of 5 g vaginally every second day for 16 weeks, and followed for a further 12 weeks off-treatment. The primary endpoint was recurrence of bacterial vaginosis (presence of ≥3 Amsel criteria) at or by Week 16. Secondary endpoints of recurrence of bacterial vaginosis at or by Week 16 included time to recurrence, subject-reported symptoms of bacterial vaginosis, individual Amsel criteria, Nugent score 7-10, and the composite of Amsel criteria and Nugent score. Adverse events were monitored throughout the study. Results: Astodrimer 1% Gel was superior to placebo for the primary and many secondary efficacy measures. At or by Week 16, bacterial vaginosis recurred in 44.2% (130/294) of women receiving astodrimer and 54.3% (158/291) receiving placebo (P = .015). Time to recurrence of bacterial vaginosis was significantly longer for women receiving astodrimer compared with placebo (Kaplan-Meier survival curves, P = .007). Recurrence of subject-reported symptoms at or by Week 16 was also significantly lower in the astodrimer arm compared with placebo (vaginal odor and/or discharge, 27.9% [75/269] vs 40.6% [108/266], P = .002). A significantly lower proportion of patients receiving astodrimer compared with placebo had recurrence of bacterial vaginosis at or by Week 16 by other secondary measures, including individual Amsel criteria (vaginal discharge and clue cells), Nugent score 7-10, and composite of Nugent score and Amsel criteria. Recurrence of subject-reported bacterial vaginosis symptoms, vaginal odor and/or discharge, was significantly lower in the astodrimer arm compared with placebo up to 8 weeks after cessation of therapy (36.1% [97/269] vs 45.5% [121/266], P = .027). During the 12-week follow-up, recurrence of ≥3 Amsel criteria after cessation of therapy in women given astodrimer was lower than in those given placebo, but the differences were not statistically significant. Adverse events were infrequent, and rates were similar between placebo and astodrimer groups, except for vulvovaginal candidiasis and urinary tract infection, which occurred more often in women receiving astodrimer. Conclusions: Astodrimer 1% Gel, administered every second day for 16 weeks, was effective and superior to placebo for prevention of recurrent bacterial vaginosis in women with a history of recurrent BV, and was well-tolerated. These results support a role for Astodrimer 1% Gel as an effective long-term treatment to prevent recurrent bacterial vaginosis that avoids potential issues associated with conventional antibiotics.

An effective response to the ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will involve a range of complementary preventive modalities. The current studies were conducted to evaluate the in vitro SARS-CoV-2 antiviral and virucidal (irreversible) activity of astodrimer sodium, a dendrimer with broad spectrum antimicrobial activity, including against enveloped viruses in in vitro and in vivo models, that is marketed for antiviral and antibacterial applications. We report that astodrimer sodium inhibits replication of SARS-CoV-2 in Vero E6 and Calu-3 cells, with 50% effective concentrations (EC 50 ) for i) reducing virus-induced cytopathic effect of 0.002 to 0.012 mg/mL in Vero E6 cells, and ii) infectious virus release by plaque assay of 0.019 to 0.032 mg/mL in Vero E6 cells and 0.031 to 0.037 mg/mL in Calu-3 cells. The selectivity index (SI) in these assays was as high as 2197. Astodrimer sodium was also virucidal, irreversibly reducing SARS-CoV-2 infectivity by >99.9% (>3 log 10 ) within 1 minute of exposure, and up to >99.999% (>5 log 10 ) shown at astodrimer sodium concentrations of 10 to 30 mg/mL in Vero E6 and Calu-3 cell lines. Astodrimer sodium also inhibited infection in a primary human airway epithelial cell line. The data were similar for all investigations and were consistent with the potent antiviral and virucidal activity of astodrimer sodium being due to irreversible inhibition of virus-host cell interactions, as previously demonstrated for other viruses. Further studies will confirm if astodrimer sodium binds to SARS-CoV-2 spike protein and physically blocks initial attachment of the virus to the host cell. Given the in vitro effectiveness and significantly high SI, astodrimer sodium warrants further investigation for potential as a topically administered agent for SARS-CoV-2 therapeutic applications.

Strategies to combat COVID-19 require multiple ways to protect vulnerable people from infection. SARS-CoV-2 is an airborne pathogen and the nasal cavity is a primary target of infection. The K18-hACE2 mouse model was used to investigate the anti-SARS-CoV-2 efficacy of astodrimer sodium formulated in a mucoadhesive nasal spray. Animals received astodrimer sodium 1% nasal spray or PBS intranasally, or intranasally and intratracheally, for 7 days, and they were infected intranasally with SARS-CoV-2 after the first product administration on Day 0. Another group was infected intranasally with SARS-CoV-2 that had been pre-incubated with astodrimer sodium 1% nasal spray or PBS for 60 min before the neutralisation of test product activity. Astodrimer sodium 1% significantly reduced the viral genome copies (>99.9%) and the infectious virus (~95%) in the lung and trachea vs. PBS. The pre-incubation of SARS-CoV-2 with astodrimer sodium 1% resulted in a significant reduction in the viral genome copies (>99.9%) and the infectious virus (>99%) in the lung and trachea, and the infectious virus was not detected in the brain or liver. Astodrimer sodium 1% resulted in a significant reduction of viral genome copies in nasal secretions vs. PBS on Day 7 post-infection. A reduction in the viral shedding from the nasal cavity may result in lower virus transmission rates. Viraemia was low or undetectable in animals treated with astodrimer sodium 1% or infected with treated virus, correlating with the lack of detectable viral replication in the liver. Similarly, low virus replication in the nasal cavity after treatment with astodrimer sodium 1% potentially protected the brain from infection. Astodrimer sodium 1% significantly reduced the pro-inflammatory cytokines IL-6, IL-1α, IL-1β, TNFα and TGFβ and the chemokine MCP-1 in the serum, lung and trachea vs. PBS. Astodrimer sodium 1% nasal spray blocked or reduced SARS-CoV-2 replication and its sequelae in K18-hACE2 mice. These data indicate a potential role for the product in preventing SARS-CoV-2 infection or for reducing the severity of COVID-19.

An effective response to the ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will involve a range of complementary preventive modalities. The current studies were conducted to evaluate the in vitro SARS-CoV-2 antiviral and virucidal activity of astodrimer sodium, a dendrimer with broad spectrum antimicrobial activity, including against enveloped viruses in in vitro and in vivo models, that is marketed for antiviral and antibacterial applications. We report that astodrimer sodium inhibits replication of SARS-CoV-2 in Vero E6 and Calu-3 cells, with 50% effective concentrations (EC50) for i) reducing virus-induced cytopathic effect of 0.002 to 0.012 mg/mL in Vero E6 cells, and ii) infectious virus release by plaque assay of 0.019 to 0.032 mg/mL in Vero E6 cells and 0.031 to 0.037 mg/mL in Calu-3 cells. The selectivity index (SI) in these assays was as high as 2197. Astodrimer sodium was also virucidal, reducing SARS-CoV-2 infectivity by >99.9% (>3 log10) within 1 minute of exposure, and up to >99.999% (>5 log10) shown at astodrimer sodium concentrations of 10 to 30 mg/mL in Vero E6 and Calu-3 cell lines. Astodrimer sodium also inhibited infection in a primary human airway epithelial cell line. The data were similar for all investigations and were consistent with the potent antiviral and virucidal activity of astodrimer sodium being due to inhibition of virus-host cell interactions, as previously demonstrated for other viruses. Further studies will confirm if astodrimer sodium binds to SARS-CoV-2 spike protein and physically blocks initial attachment of the virus to the host cell. Given the in vitro effectiveness and significantly high SI, astodrimer sodium warrants further investigation for potential as a nasally administered or inhaled antiviral agent for SARS-CoV-2 prevention and treatment applications.