Dataset Information

Provision of antioxidant therapy in hemodialysis (PATH): a randomized clinical trial.

ABSTRACT: Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus ?-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.

SUBMITTER: Himmelfarb J

PROVIDER: S-EPMC3935590 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Provision of antioxidant therapy in hemodialysis (PATH): a randomized clinical trial.

Himmelfarb Jonathan J Ikizler T Alp TA Ellis Charles C Wu Pingsheng P Shintani Ayumi A Dalal Sanjay S Kaplan Mark M Chonchol Michel M Hakim Raymond M RM

Journal of the American Society of Nephrology : JASN 20131226 3

Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acu ...[more]

PMID: 24371300

Similar Datasets

Project description:ImportanceCast nephropathy is the main cause of acute kidney injury in multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Strategies to rapidly remove nephrotoxic serum-free light chains combined with novel antimyeloma agents have not been evaluated prospectively.ObjectiveTo compare the hemodialysis independence rate among patients newly diagnosed with myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer (with very large membrane pores and high permeability to immunoglobulin light chains) or a conventional high-flux dialyzer (with small pores and lower permeability).Design, setting, and participantsRandomized clinical trial involving 98 patients with biopsy-proven myeloma cast nephropathy requiring hemodialysis treated at 48 French centers between July 2011 and June 2016; the final date of follow-up was June 29, 2016.InterventionsIntensive hemodialysis (eight 5-hour sessions over 10 days) with either a high-cutoff dialyzer (46 patients) or a conventional high-flux dialyzer (48 patients). All patients received the same chemotherapy regimen of bortezomib and dexamethasone.Main outcomes and measuresPrimary end point was hemodialysis independence at 3 months; secondary end points: hemodialysis independence rates at 6 and 12 months, hemodialysis- and chemotherapy-related adverse events, and death.ResultsAmong 98 randomized patients, 94 (96%) (median age, 68.8 years [interquartile range, 61.2-75.3 years]; 45% women) were included in the modified intent-to-treat analysis. The hemodialysis independence rate at 3 months was 41.3% (n = 19) in the high-cutoff hemodialysis group vs 33.3% (n = 16) in the conventional hemodialysis group (between-group difference, 8.0% [95% CI, -12.0% to 27.9%], P = .42); at 6 months, the rate was 56.5% (n = 26) vs 35.4% (n = 17), respectively (between-group difference, 21.1% [95% CI, 0.9% to 41.3%], P = .04); and at 12 months, the rate was 60.9% (n = 28) vs 37.5% (n = 18) (between-group difference, 23.4% [95% CI, 3.2% to 43.5%], P = .02). The incidence of hemodialysis-related adverse events was 43% in the high-cutoff hemodialysis group vs 39% in the conventional hemodialysis group; chemotherapy-related serious adverse events, 39% vs 37%, respectively; and at 12 months, 9 patients vs 10 patients died.Conclusions and relevanceAmong patients with myeloma cast nephropathy treated with a bortezomib-based chemotherapy regimen, the use of high-cutoff hemodialysis compared with conventional hemodialysis did not result in a statistically significant difference in hemodialysis independence at 3 months. However, the study may have been underpowered to identify an early clinically important difference.Trial registrationclinicaltrials.gov Identifier: NCT01208818.

Project description:This study aimed to examine the effects of carbocysteine in OSAS patients.A total of 40 patients with moderate to severe obstructive sleep apnea syndrome (OSAS) were randomly divided into two groups. One group was treated with 1500 mg carbocysteine daily, and the other was treated with continuous positive airway pressure (CPAP) at night. Before treatment and after 6 weeks of treatment, all patients underwent polysomnography and completed questionnaires. Treatment compliance was compared between the two groups. Plasma was collected for various biochemical analyses. Endothelial function was assessed with ultrasound in the carbocysteine group.The proportion of patients who fulfilled the criteria for good compliance was higher in the carbocysteine group (n = 17) than in the CPAP group (n = 11; 100% vs. 64.7%). Compared with baseline values, the carbocysteine group showed significant improvement in their Epworth Sleepiness Scale score (10.18 ± 4.28 vs. 6.82 ± 3.66; P ? 0.01), apnea-hypopnea index (55.34 ± 25.03 vs. 47.56 ± 27.32; P ? 0.01), time and percentage of 90% oxygen desaturation (12.66 (2.81; 50.01) vs. 8.9 (1.41; 39.71); P ? 0.01), and lowest oxygen saturation level (65.88 ± 14.86 vs. 70.41 ± 14.34; P ? 0.01). Similar changes were also observed in the CPAP group. The CPAP group also showed a decreased oxygen desaturation index and a significant increase in the mean oxygen saturation after treatment, but these increases were not observed in the carbocysteine group. Snoring volume parameters, such as the power spectral density, were significantly reduced in both groups after the treatments. The plasma malondialdehyde level decreased and the superoxide dismutase and nitric oxide levels increased in both groups. The endothelin-1 level decreased in the CPAP group but did not significantly change in the carbocysteine group. Ultrasonography showed that the intima-media thickness decreased (0.71 ± 0.15 vs. 0.66 ± 0.15; P ? 0.05) but that flow-mediated dilation did not significantly change in the carbocysteine group.Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation.ClinicalTrials.gov NCT02015598.

Project description:BACKGROUND:Anemia of chronic kidney disease is associated with adverse outcomes and a reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have improved anemia management, and 2 agents are available in Canada, epoetin alfa (EPO) and darbepoetin alfa (DA). EPO and DA are considered equally effective in achieving target hemoglobin (Hb), but it is not clear whether there is a cost difference. There have been few head-to-head comparisons; most published studies are observational switch studies. OBJECTIVE:To compare the cost of DA and EPO and to determine the dose conversion ratio over a 12-month period. DESIGN:Randomized controlled trial. SETTING:Canadian outpatient hemodialysis center. PATIENTS:Eligible patients were adult hemodialysis patients requiring ESA therapy. MEASUREMENTS:The primary outcome was ESA cost (Can$) per patient over 12 months. Secondary outcomes included the dose conversion ratio, deviation from target ranges in anemia indices, iron dose and cost, and time and number of dose changes. METHODS:An open-label randomized controlled trial of intravenous (IV) DA versus EPO was conducted in 50 hemodialysis patients. Participants underwent a minimum 6-week run-in phase followed by a 12-month active study phase. ESA and iron were dosed using a study algorithm. RESULTS:The median cost was $4179 (interquartile range [IQR]: $2416-$5955) for EPO and $2303 (IQR: $1178-$4219) for DA with a difference of $1876 (P = .02). The dose conversion ratio was 280:1 (95% confidence interval [CI]: 197-362:1) at the end of the run-in phase, 360:1 (95% CI: 262-457:1) at the 3-month point of the active phase, and 382:1 (95% CI: 235-529:1) at the 6-month point of the active phase. There were no significant differences between the 2 groups in weekly iron dose, Hb, serum ferritin, or transferrin saturation. The number of dose changes and the time to Hb stability were similar. LIMITATIONS:Results may not be generalizable to hemodialysis units without algorithm-based anemia management, with subcutaneous ESA administration, or to the nondialysis chronic kidney disease population. The effective conversion ratio between EPO and DA is known to increase at higher doses; the Hb targets used in the study were slightly higher than those recommended today so it is possible that the doses used were also higher. Because of this, the cost savings estimated for DA could differ somewhat from the savings realizable in current practice. CONCLUSIONS:In this study of hemodialysis patients with comparable anemia management, IV DA cost $1876 less per year per patient than IV EPO. The dose conversion ratio was greater than 350:1 by the 3-month point. TRIAL REGISTRATION:ClinicalTrials.gov (NCT02817555).

Dataset Information

Provision of antioxidant therapy in hemodialysis (PATH): a randomized clinical trial.

Publications

Provision of antioxidant therapy in hemodialysis (PATH): a randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets