scholarly journals MO214EVALUATION OF THE EFFECT OF A POTASSIUM BINDER ON ARRHYTHMIA-RELATED CARDIOVASCULAR OUTCOMES IN PATIENTS ON CHRONIC HAEMODIALYSIS WITH RECURRENT HYPERKALAEMIA: DESIGN AND RATIONALE FOR THE SODIUM ZIRCONIUM CYCLOSILICATE DIALIZE-OUTCOMES STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Steven Fishbane ◽  
Michel Jadoul ◽  
Laura M Dember ◽  
Csaba Kovesdy ◽  
Ian Sabir ◽  
...  
Keyword(s):  
Ventricular Tachyarrhythmia ◽  
Composite Endpoint ◽  
Primary Objective ◽  
Controlled Study ◽  
Chronic Haemodialysis ◽  
Double Blind ◽  
Once Daily ◽  
Sodium Zirconium ◽  
Outcomes Study ◽  
Sodium Zirconium Cyclosilicate

Abstract Background and Aims Patients with end-stage renal disease (ESRD) on chronic haemodialysis are at an elevated risk of arrhythmias that can increase the risk of sudden cardiac death (SCD) and stroke, along with the need for hospitalisation and interventions. These arrhythmias may be exacerbated by pre-dialysis hyperkalaemia and rapid serum potassium (sK+) shifts that occur during and after haemodialysis sessions. The DIALIZE study (NCT03303521) demonstrated that sodium zirconium cyclosilicate (SZC) was an effective and well-tolerated treatment for pre-dialysis hyperkalaemia, when administered once-daily on non-dialysis days for 8 weeks in patients with ESRD undergoing chronic haemodialysis. The DIALIZE-Outcomes study (EudraCT 2020-005561-14) will evaluate the effect of SZC treatment on arrhythmia-related cardiovascular (CV) outcomes in patients with ESRD on chronic haemodialysis with recurrent hyperkalaemia. Method The DIALIZE-Outcomes study is an international, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, to be conducted at ∼300 study sites across ∼20 countries. Adults (≥18 years of age) with ESRD on haemodialysis three times weekly and with recurrent pre-dialysis sK+ ≥5.5 mmol/L after the long interdialytic interval (LIDI) will be eligible for enrolment. Approximately 2300 patients will be randomised 1:1 to SZC or placebo (Figure), starting at 5 g orally once daily on non-dialysis days (4 days/week) and uptitrated weekly in 5 g increments (maximum 15 g) to achieve pre-dialysis sK+ 4.0–5.0 mmol/L after the LIDI. Dose adjustments after the uptitration phase will be guided by sK+ monitoring, as per clinical practice. The primary objective is to evaluate the efficacy of SZC versus placebo in reducing the incidence of the primary composite endpoint of time to first occurrence of SCD, stroke or hospitalisation/intervention/emergency department visit due to arrhythmias (atrial fibrillation, bradycardia, asystole, ventricular tachyarrhythmia). Secondary endpoints include the efficacy of SZC versus placebo in maintaining normokalaemia (sK+ 4.0–5.5 mmol/L after the LIDI) and preventing severe hyperkalaemia (sK+ ≥6.5 mmol/L after the LIDI) at 1 year (assessed through measurement of sK+ at the 12-month study visit), and time to occurrence of CV outcomes. Safety and tolerability of SZC versus placebo will also be evaluated. The study is event-driven, with patients remaining on study treatment until a pre-specified number of primary endpoint events (770) has occurred. The anticipated average treatment period is ∼25 months. Conclusion The DIALIZE-Outcomes study is the first evaluation of a K+ binder in improving CV outcomes in patients with ESRD on chronic haemodialysis and with recurrent hyperkalaemia. The study findings will provide valuable information that may help to further our understanding of the relationship between hyperkalaemia and CV morbidity and mortality in patients on chronic haemodialysis, and to optimise treatment regimens in this high CV and SCD risk population.

scholarly journals A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia

2019 ◽  
Vol 30 (9) ◽  
pp. 1723-1733 ◽  
Author(s):  
Steven Fishbane ◽  
Martin Ford ◽  
Masafumi Fukagawa ◽  
Kieran McCafferty ◽  
Anjay Rastogi ◽  
...  
Keyword(s):  
Serum Potassium ◽  
Rescue Therapy ◽  
Controlled Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Interdialytic Weight Gain ◽  
Sodium Zirconium ◽  
Efficacy Outcome ◽  
Sodium Zirconium Cyclosilicate

BackgroundPatients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients.MethodsIn the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g. The primary efficacy outcome was proportion of patients during the 4-week stable-dose evaluation period who maintained predialysis serum potassium of 4.0–5.0 mmol/L during at least three of four hemodialysis treatments after the long interdialytic interval and did not require urgent rescue therapy to reduce serum potassium.ResultsIn total, 196 patients (mean [standard deviation (SD)] age =58.1 [13.7] years old) were randomized to sodium zirconium cyclosilicate or placebo. Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001). Rescue therapy to reduce serum potassium during the treatment period was required by 2.1% of patients taking sodium zirconium cyclosilicate versus 5.1% taking placebo. Serious adverse events occurred in 7% and 8% of patients in sodium zirconium cyclosilicate and placebo groups, respectively. The two groups displayed comparable interdialytic weight gain. There were few episodes of hypokalemia.ConclusionsSodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.

scholarly journals Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double‐blind, Placebo‐controlled Study (ENERGIZE)

2020 ◽  
Vol 27 (6) ◽  
pp. 475-486 ◽  
Author(s):  
W. Frank Peacock ◽  
Zubaid Rafique ◽  
Konstantin Vishnevskiy ◽  
Edward Michelson ◽  
Elena Vishneva ◽  
...  
Keyword(s):  
Phase Ii ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Sodium Zirconium ◽  
Sodium Zirconium Cyclosilicate

scholarly journals Evaluating the Effect of Intraoperative Dextrose 10% Administration on Reducing Postoperative Nausea and Vomiting after Laparoscopic Surgery

2019 ◽  
Vol 13 (1) ◽  
pp. 78-85
Author(s):  
Ashraf Nabil Saleh ◽  
Dalia Fahmy Emam ◽  
Mohamed Mohamed Kamal
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Postoperative Nausea ◽  
Postoperative Nausea And Vomiting ◽  
Study Groups ◽  
Primary Objective ◽  
Nausea And Vomiting ◽  
Controlled Study ◽  
Double Blind ◽  
Female Patients ◽  
Medication Consumption

Background: Although PONV is usually self-limiting or is treated without sequelae, the incidence of PONV could be as high as 70% to 80% in high-risk populations such as female sex, obese patients, age younger than 40 years, nonsmoker patients, history of PONV or motion sickness. Objectives: The study aimed to investigate whether dextrose 10% decreases the incidence of postoperative nausea and vomiting in female patients undergoing laparoscopic cholecystectomy Materials and Methods: This prospective, double-blind randomized placebo-controlled study comprised 130 ASA physical status I and II nonsmoker female patients, 20-40 years of age, scheduled for laparoscopic cholecystectomy at Ain Sham University – Assembled operating theater from August 2018 to October 2018. Patients were arbitrarily divided into two study groups of 65 patients each. Group LR received lactated Ringer’s solution and group D received 10% dextrose. The primary objective of this study was to compare the incidence of PONV in the study treatment groups. The secondary outcomes included measurement of antiemetic medication consumption as well as blood glucose changes between groups. Results: 50 from a total of 65 participants (76.9%) in Lactated Ringer (LR) group experienced nausea. On the other hand, 30 participants only (46.2%) in dextrose (D) group were nauseated. This dissimilarity was statistically highly significant (P= 0.0003). Conclusion: In this study, dextrose 10% administration resulted in improved postoperative emesis management as explained by the lower incidence of nausea and rescue antiemetic consumption.

Treatment of relapsing-remittent multiple sclerosis with recombinant human interferon-alfa-2a: design of a randomised, placebo-controlled, double blind trial in Norway

1996 ◽  
Vol 1 (6) ◽  
pp. 372-375 ◽  
Author(s):  
H Nyland ◽  
K-M Myhr ◽  
F Lillås ◽  
AI Smievoll ◽  
T Riise ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Primary Objective ◽  
Interferon Alfa ◽  
Controlled Study ◽  
Human Interferon ◽  
New Disease ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Drug Free

A multicentre, randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of 4.5 and 9.0 MIU recombinant human interferon alfa-2a (Rof eron-A™) given thrice weekly in patients with relapsing-remittent multiple sclerosis is described. The patients are treated for 6 months followed by a 6 months drug-free period. The primary objective is to determine new disease activity analysed by monthly MRI with gadodiamide (GdDTPA-BMA, Omniscan™). The study is conducted at eight centers in Norway and is completed in January 1996.

scholarly journals A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Christine K. Bailey ◽  
Stephen Caltabiano ◽  
Alexander R. Cobitz ◽  
Chun Huang ◽  
Kelly M. Mahar ◽  
...  
Keyword(s):  
Dose Range ◽  
Hypoxia Inducible Factor ◽  
Conversion Ratio ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Once Daily ◽  
Human Erythropoietin ◽  
Dose Ranging ◽  
Baseline Hemoglobin

Abstract Background Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor currently being investigated as a treatment for anemia of chronic kidney disease (CKD) in both dialysis and nondialysis patients. In clinical studies to date, daprodustat has been administered orally as a once-daily regimen. This randomized, double-blind, placebo-controlled study characterized the initial dose-hemoglobin response as well as the efficacy and safety of three times weekly (TIW) daprodustat in hemodialysis patients switched from stable recombinant human erythropoietin (rhEPO), in accordance with a TIW hemodialysis schedule. Methods 103 patients on hemodialysis with baseline hemoglobin of 9.0 to 11.5 g/dL and previously receiving a stable dose of rhEPO or its analogs were randomized 1:1:1:1:1 to receive daprodustat 10, 15, 25, or 30 mg or placebo TIW over 29 days. Results Mean baseline hemoglobin was 10.6 g/dL for the placebo group and each daprodustat cohort. Daprodustat produced dose-dependent changes in mean hemoglobin from baseline to day 29. Using a Bayesian approach, the estimated dose conversion ratio between once-daily and TIW daprodustat was ~ 2.0 across the evaluated dose range using an Emax model. Daprodustat was generally well tolerated, with an adverse event (AE) profile consistent with the hemodialysis population. Conclusions These data help inform the appropriate dose conversion ratio to be applied to daily doses to obtain equivalent daprodustat TIW doses and suggest TIW treatment with daprodustat can treat anemia of CKD safely, supporting future long-term studies for this indication using a TIW dosing regimen. Trial registration ClinicalTrials.gov Identifier: NCT02689206; date registered: 02/11/2016.

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