A phase Ib, open-label, single arm study to assess the safety, pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end-stage renal disease

2017 ◽  
Vol 32 (1) ◽  
pp. e13155 ◽  
Author(s):  
Bassam G. Abu Jawdeh ◽  
Ervin Steve Woodle ◽  
Abbie D. Leino ◽  
Paul Brailey ◽  
Simon Tremblay ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Open Label ◽  
Phase Ib ◽  
Stage Renal Disease ◽  
End Stage

Pharmacokinetics, safety, and tolerability of edoxaban in end-stage renal disease subjects undergoing haemodialysis

2015 ◽  
Vol 113 (04) ◽  
pp. 719-727 ◽  
Author(s):  
Thomas Marbury ◽  
Nobuko Matsushima ◽  
Shuquan Chen ◽  
Prachi K. Wickremasingha ◽  
Ling He ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Phase 1 ◽  
Factor Xa ◽  
Chronic Haemodialysis ◽  
Open Label ◽  
Open Label Phase ◽  
Stage Renal Disease ◽  
A Minor ◽  
End Stage

SummaryEdoxaban is an oral, direct, once-daily, factor Xa inhibitor developed for stroke prevention in patients with atrial fibrillation and for the treatment and secondary prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism. Among elderly patients who require anticoagulation therapies, some may have end-stage renal disease (ESRD). This open-label, phase 1, randomised, two-way crossover study was conducted to evaluate the pharmacokinetics of edoxaban in 10 subjects on haemodialysis. Eligible subjects with ESRD on chronic haemodialysis received a single, oraldose of edoxaban 15 mg 2 hours (h) prior to (on-dialysis) or in between (off-dialysis) haemodialysis sessions. Haemodialysis resulted in a minor decrease in mean total exposure (AUC0-∞; 676.2 ng⋅h/ml) as compared with that observed in subjects off-dialysis (691.7 ng⋅h/ml). Mean maximum observed plasma concentration (Cmax) values were comparable between on-dialysis and off-dialysis treatments (53.3 vs 56.3 ng/ml, respectively). Mean apparent total body clearance (CL/F) values were 24.1 and 22.5 l/h during the on-dialysis and off-dialysis treatment periods, respectively. Dialyser clearance was 5.7 l/h and haemodialysis clearance was 6.1 l/h. Haemodialysis clearance was only 6.1 l/h, suggesting that it only accounts for one-fourth of the total clearance in these subjects. A single, oral dose of 15 mg of edoxaban was well tolerated by subjects with ESRD. In conclusion, based on these single-dose PK data, a supplementary dose of edoxaban may not be required following a haemodialysis session. Importantly, haemodialysis is not an effective mechanism for removal of edoxaban from the blood.

scholarly journals Activation of oxidative stress, comorbidity and survival of end-stage renal disease patients treated with hemodialysis

2021 ◽  
pp. 67-77
Author(s):  
I. Shifris ◽  
L. Korol ◽  
Е. Krasiuk ◽  
S. Dudar
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Quantitative Assessment ◽  
Chronic Obstructive ◽  
Serum Concentrations ◽  
Comorbid Conditions ◽  
Open Label ◽  
Stage Renal Disease ◽  
End Stage

Abstract. The aim of the study was to analyze the characteristics of serum concentrations of oxidative stress (OS) markers depending on the quantitative assessment of comorbidity and taking into account the most informative indicators of OS, to prospectively assess changes in comorbid status, death rates and individual comorbid conditions in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD). Methods. The cohort prospective open-label study included 156 patients with ESRD, treated with HD. The study was conducted in two stages. In the first – the structure and quantitative assessment of comorbid diseases, determination of serum concentrations of oxidative stress (OS) markers and their analysis depending on the comorbid status were studied. On the second – taking into account the defined threshold values (Cut-off) of the most informative markers of the OS, an assessment of changes in comorbid status, frequency of comorbid conditions and fatal events done. A modified polymorbidity index (MPI) was calculated to assess comorbid status. The concentration of OS serum markers was determined by spectrophotometric method. Statistical analysis was performed by using "MedCalc", version 19.3 (Ostend, Belgium). Results. Serum concentrations of all prooxidant markers were significantly higher and antioxidant markers were significantly lower in the HD patients with high comorbid status compared to those of patients with low comorbidity (p<0.0001). Correlation analysis between MIP and the studied OS markers showed that the largest correlation (rho=0.874) was established with the serum concentration of malondialdehyde (MDAs). During the observation period in the group of patients with a concentration of MDAs > 668.72 μmol/ml found a significant, compared with the group with a biomarker content ≤ 668.72 μmol/ml, an increase in the proportion of patients with chronic obstructive pulmonary disease (COPD) (by 81.84 % vs 28.48 %; p<0.0001), cardiovascular diseases (CVD) (by 56.0 % vs 36.4 %; p=0.019) and cerebrovascular (CEVD) diseases (by 73.33 % vs 30.42 %; p<0.0001). The proportion of patients with fractures in the group of patients with MDAs > 668.72 μmol/l increased fourfold (p=0.0140). The increase in MIP is 34.11 % vs 17.1 % (p<0.0001), five-year cumulative survival – 45.3 % vs 63.3 % (p=0.0312; HR – 2,1527, 95% CI: 1,2458 –3,7199), five-year CV survival – 61,6 % vs 80.8 % (p=0.0094; HR – 2.7955, 95% CI: 1.3664 – 5.7191) in groups with MDAs > 668.72 and ≤ 668.72 μmol/ml, respectively. Conclusions. In patients with ESRD, treated with HD, serum concentrations of MDAs > 668.72 μmol/l is a biochemical determinant of a significant increase, in the medium term, the number of comorbid conditions, deaths, fatal CV and CEVD events, the proportion of patients with COPD, fractures, CVD and CEVD, reduction of cumulative and CV survival.

scholarly journals Randomised, open-label, multicentre trial comparing haemodialysis plus haemoperfusion versus haemodialysis alone in adult patients with end-stage renal disease (HD/HP vs HD): study protocol

BMJ Open ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. e022169
Author(s):  
Wei Lu ◽  
Geng-Ru Jiang
Keyword(s):  
Renal Disease ◽  
Study Protocol ◽  
End Stage Renal Disease ◽  
Multicentre Trial ◽  
Heart Function ◽  
Adult Patients ◽  
Open Label ◽  
All Cause Mortality ◽  
Stage Renal Disease ◽  
End Stage

IntroductionHaemodialysis (HD) is the cornerstone treatment for patients with end-stage renal disease (ESRD). However, highly protein bound or large molecular weight uremic toxins such as phenolic and indolic compounds and homocysteine, which are associated with adverse outcomes such as cardiovascular disease of patients with ESRD, are difficult to remove via HD but can be effectively eliminates by haemoperfusion (HP). The proposed trial (referred to as HD/HP vs HD below) is a randomised, open-label, multicentre trial comparing HD plus HP versus HD alone in adult patients with ESRD. The primary endpoint measure is all-cause mortality.Methods and analysisWe plan to enrol 1364 maintenance HD patients from 11 medical centres in Shanghai. Participants will be randomised to receive HD plus HP or HD alone at a 1:1 ratio after 1-month run-in period. In both arms, patients will receive low-flux HD at a frequency of two times a week and haemodiafiltration at a frequency of once a week. In the intervention group, subjects also received HP once every 2 weeks. Follow-up is scheduled at 3, 6, 12, 18 and 24 months after randomisation, and will consist the following: routine physical examinations, standard lab panels (blood routine, liver/residual kidney functions, tests of the coagulation system, etc), dialysis adequacy (standard Kt/V), chest X-ray, ECG, echocardiography, heart function rating. Adverse events will be assessed according to the international conference on harmonisation guidelines. The primary outcome is 24-month all-cause mortality. Secondary outcomes will include cardiovascular-related mortality, the occurrence of major cardiovascular events and the quality of life.Ethics and disseminationThe study protocol has been approved by the Ethical Committees of all 11 participating centres. Clinical Research Unit of Xin Hua Hospital will oversee the study. The results will be presented at national and international academic meetings, and submitted to peer-reviewed journals for publications.Trial registration numberNCT03227770; Pre-results.

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