Pharmacokinetics of Remdesivir and GS-441524 during PIRRT and Seraph 100 Therapy

Schmidt, Julius J.; Bode‐Böger, Stefanie M.; Martens‐Lobenhoffer, Jens; Hoeper, Marius M.; Kielstein, Jan T.

doi:10.2215/cjn.17601120

Cited by 12 publications

(9 citation statements)

References 5 publications

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“…There was no significant increase in the DIC-score during the Seraph ® 100 treatment (before: 3 [2][3][4], after: 3 [3,4], p = 0.17). Although we did not measure drug levels of anti-infectives during this study, neither extensive in vitro studies using human plasma and a Seraph ® 100 in a hemoperfusion setting [27,28] nor anecdotal clinical reports [29] suggest clinical significant removal of anti-infective drugs. Interestingly, this holds true for tacrolimus and mycofenolatemofetil [30].…”

Section: Safety-laboratory Datamentioning

confidence: 99%

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Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study

et al. 2022

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Background Bacterial burden as well as duration of bacteremia influence the outcome of patients with bloodstream infections. Promptly decreasing bacterial load in the blood by using extracorporeal devices in addition to anti-infective therapy has recently been explored. Preclinical studies with the Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100), which consists of heparin that is covalently bound to polymer beads, have demonstrated an effective binding of bacteria and viruses. Pathogens adhere to the heparin coated polymer beads in the adsorber as they would normally do to heparan sulfate on cell surfaces. Using this biomimetic principle, the Seraph® 100 could help to decrease bacterial burden in vivo. Methods This first in human, prospective, multicenter, non-randomized interventional study included patients with blood culture positive bloodstream infection and the need for kidney replacement therapy as an adjunctive treatment for bloodstream infections. We performed a single four-hour hemoperfusion treatment with the Seraph® 100 in conjunction with a dialysis procedure. Post procedure follow up was 14 days. Results Fifteen hemodialysis patients (3F/12 M, age 74.0 [68.0–78.5] years, dialysis vintage 28.0 [11.0–45.0] months) were enrolled. Seraph® 100 treatment started 66.4 [45.7–80.6] hours after the initial positive blood culture was drawn. During the treatment with the Seraph® 100 with a median blood flow of 285 [225–300] ml/min no device or treatment related adverse events were reported. Blood pressure and heart rate remained stable while peripheral oxygen saturation improved during the treatment from 98.0 [92.5–98.0] to 99.0 [98.0–99.5] %; p = 0.0184. Four patients still had positive blood culture at the start of Seraph® 100 treatment. In one patient blood cultures turned negative during treatment. The time to positivity (TTP) was increased between inflow and outflow blood cultures by 36 [− 7.2 to 96.3] minutes. However, overall TTP increase was not statistical significant. Conclusions Seraph® 100 treatment was well tolerated. Adding Seraph® 100 to antibiotics early in the course of bacteremia might result in a faster resolution of bloodstream infections, which has to be evaluated in further studies. Trail registration: ClinicalTrials.gov Identifier: NCT02914132, first posted September 26, 2016.

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Section: Safety-laboratory Datamentioning

confidence: 99%

“…Therefore, other renal replacement therapy modalities could not be investigated in this study. However, outside of this investigation the device has been used in the setting of prolonged intermittent renal replacement therapy [29], continues kidney replacement therapy [31] and standalone hemoperfusion [32].…”

Section: Study Limitationsmentioning

confidence: 99%

Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study

et al. 2022

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“…The optimal dose leading to the maximal antiviral efficacy of remdesivir in humans is currently unknown, but modeling and simulation studies suggest that the current dosing regimen might be suboptimal ( 14 , 15 ). These studies were performed using pharmacokinetic data from healthy individuals, whereas studies regarding the pharmacokinetics of remdesivir in COVID-19 patients are limited to case series with scarce sampling schedules and a single pharmacokinetic study with only GS-441524 concentrations ( 16 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics of Remdesivir and GS-441524 in Hospitalized COVID-19 Patients

Leegwater

Moes

Bosma

et al. 2022

Antimicrob Agents Chemother

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“…One concern is that the device could remove beneficial medications such as remdesivir and dexamethasone. Although data are limited, the device does not appear to remove remdesivir ( 30 ). Although binding of dexamethasone has not been examined, it is a nonionic molecule and is not known to interfere with heparin therapy.…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19

Chitty¹,

S²,

Rifkin³

et al. 2022

Critical Care Explorations

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OBJECTIVES: The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19. DESIGN: Retrospective cohort study. SETTING: Nine participating ICUs. PATIENTS: COVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53). INTERVENTION: Treatment with Seraph 100. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41–65) compared with controls (median age, 64 yr; IQR, 56–69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0–3) compared with the control group (3; IQR, 2–4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9–17) compared with controls (16; IQR, 12–21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded. CONCLUSIONS: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.

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Pharmacokinetics of Remdesivir and GS-441524 during PIRRT and Seraph 100 Therapy

Cited by 12 publications

References 5 publications

Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study

Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study

Population Pharmacokinetics of Remdesivir and GS-441524 in Hospitalized COVID-19 Patients

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19

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