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

Efficacy of Phenazone in the Treatment of Acute Migraine Attacks: A Double-Blind, Placebo-Controlled, Randomized Study

Cephalalgia ◽  
2004 ◽  
Vol 24 (10) ◽  
pp. 888-893 ◽  
Author(s):  
H Göbel ◽  
A Heinze ◽  
U Niederberger ◽  
T Witt ◽  
V Zumbroich
Keyword(s):  
Adverse Events ◽  
Randomized Study ◽  
Controlled Study ◽  
Acute Migraine ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Number Of Patients ◽  
Significant Difference ◽  
Main Target

In this study we compared the efficacy of 1000 mg phenazone with that of placebo in the treatment of acute migraine attacks in a randomized double-blind, placebo-controlled study of 208 patients. The main target criterion was the number of patients with a pain reduction from severe or moderate to slight or no pain 2 h after taking the pain medication. The percentage of patients satisfying the main target criterion was 48.6% for phenazone and 27.2% ( P < 0.05) for placebo. Freedom from pain after 2 h was reported by 27.6% with phenazone treatment and 13.6% ( P < 0.05) with placebo. Compared with placebo, the phenazone treatment also resulted in a significant improvement in the associated migraine symptoms of nausea, phonophobia and photophobia. Of patients treated with phenazone 11.4%, and 5.8% of those treated with placebo reported adverse events. There was no significant difference between the groups with regard to numbers of patients with adverse events. No serious adverse events occurred. The results show that phenazone at a dosage of 1000 mg is effective and well tolerated in the treatment of acute migraine attacks.

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.

Safety and efficacy of glycopyrrolate as a premedication for endoscopic submucosal dissection: a randomized, double-blind, placebo-controlled study

Endoscopy ◽  
2017 ◽  
Vol 49 (10) ◽  
pp. 949-956 ◽  
Author(s):  
Eui Kim ◽  
Min Um ◽  
Kyoung Kim ◽  
Jung Kim ◽  
Su Kim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Endoscopic Submucosal Dissection ◽  
Medical Center ◽  
Controlled Trial ◽  
Controlled Study ◽  
Research Information ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Submucosal Dissection

Abstract Background and study aims Anticholinergic premedication has not been validated for endoscopic submucosal dissection (ESD). In this randomized, double-blind, placebo-controlled trial, we investigated the efficacy and safety of glycopyrrolate as a premedication for ESD. Methods A total of 196 patients undergoing ESD at a single tertiary medical center between December 2014 and February 2016 were randomly allocated to receive one of the following two premedications: glycopyrrolate (0.004 mg/kg intramuscularly [IM]) or placebo (2.0 mL normal saline solution IM). All patients received the premedication 30 minutes prior to ESD in a double-blind manner. The endoscopists reported the ease of performing the procedure and the incidence of secretion-induced hypoxemia, cough, and other procedure-related adverse events. Results Glycopyrrolate and placebo were received by 96 and 100 patients, respectively. ESD was successfully performed in all patients without any serious adverse events related to sedation or ESD. The median visual analog scale for procedure ease was higher in the glycopyrrolate group at 8 (interquartile range [IQR] 7 – 9) vs. 7 (IQR 6 – 8.25); P < 0.001. The proportions of patients with secretion-induced hypoxemia (4.4 % vs. 14.3 %; P = 0.03) and cough (16.7 % vs. 35.7 %; P = 0.005) were lower in the glycopyrrolate group.  Conclusions The use of glycopyrrolate as a premedication for ESD significantly improved the ease of performing the procedure and reduced the incidence of secretion-induced hypoxemia and cough during ESD. Glycopyrrolate may be a promising premedication to ensure safe and stable ESD procedures.Trial registration: Clinical Research Information Service (CRIS): KCT0001540.

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