Hyperkalemia
Conditions
Brief summary
A Prospective, RanDomized, Multi-Center, Open-Label, Cross-Over Study of Sodium Zirconium Cyclosilicate to Control Interdialytic HyperkalemiA Following Augmentation of Dialysate Potassium: Efficacy to Reduce the Incidence of Post-Dialysis Atrial Fibrillation and Clinically SignificanT Cardiac Arrhythmias - ADAPT Trial
Detailed description
This is a prospective, open-labelled, randomized, 2x2 cross-over design study of 88 patients with end stage renal disease (ESRD) receiving routine out-patient dialysis using a standard 2.0 potassium ion (K+)/2.5 calcium ion (Ca++) dialysate bath. The overall aim of the study is to determine whether converting stable hemodialysis patients from a standard 2.0 K+/2.5 Ca+ dialysate (without Lokelma) to a 3.0 K+/2.5 Ca++ mEq dialysate supplemented with the orally administered potassium binder sodium zirconium cyclosilicate (Lokelma) to treat interdialytic hyperkalemia will reduce the incidence and duration of post-dialysis atrial fibrillation.
Interventions
Patients will use Lokelma supplementation on off-dialysis days (4 days/week) while receiving hemodialysis with 3.0 K+/2.5 Ca++ mEq dialysate bath. The individual starting dose will be 5.0 grams, and may be titrated weekly in 5.0 gram increments up to 15.0 grams to maintain K+ between 4.0 and 5.5 mEq/L.
Sponsors
AstraZeneca
NephroNet, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Chronic outpatient hemodialysis patients have high rates of rapid changes in potassium and other electrolytes critical to the generation cardiac arrythmias. A growing body of data suggests that intra-dialytic K+ levels fall to level of 2.0 or lower and are a potential major contributor to the generation of atrial fibrillation, bradycardia, and other clinically significant arrhythmias. We propose that raising the dialysate bath to 3.0 K+ from current standard of care levels of 2.0 K+ will reduce levels of hypokalemia-induced arrhythmias. We further propose that the use of sodium zirconium cyclosilicate (Lokelma) will ensure that secondary hyperkalemia is controlled following the introduction of the 3.0 K+ dialysate bath.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study-specific procedures * Female or male aged above 18 years * Patients with ESRD receiving hemodialysis three times per week for a minimum of 3 months * Patients must have two (2) pre-dialysis K+ measurements between 5.1 and 6.5 mEq/L by Piccolo POCT following the long dialytic weekends (i.e., on two consecutive Mondays for patients on a Monday-Wednesday-Friday dialysis schedule or on two consecutive Tuesdays for patients on a Tuesday-Thursday-Saturday dialysis schedule) during screening, before insertion of the cardiac loop recorder. * Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.) They should have been stable on their chosen method of birth control for a minimum of 1 month before entering the study and willing to remain on the birth control until 4 weeks after the last dose.
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in atrial Fibrillation events | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To demonstrate whether increasing the K+ concentration in a standard hemodialysis bath from 2.0 K+ /2.5 Ca++ to a 3.0 K+ /2.5 Ca++ composition with SZC will reduce the incidence of atrial fibrillation events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and duration of CSCAs (bradycardia, ventricular tachycardia and/or asystole) | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To access whether the incidence and duration of post-dialysis CSCAs (defined as bradycardia, ventricular tachycardia and/or asystole) observed during experimental treatment will be reduced compared to standard treatment. |
| Whether or not K+ outside of the 4.0 to 5.5 mEq/L safety range (Yes/No binary outcome measure). | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To determine whether the addition of oral sodium zirconium cyclosilicate (Lokelmaâ) during the 2-month treatment phase with the 3.0 K+ /2.5 Ca++ dialysate bath will reduce risk of weeks outside the K+ safety range of 4.0 to 5.5 mEq/L compared to the 2-month treatment phase with the 2.0 K+ /2.5 Ca++ dialysate bath. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation between PBUTs (IS, PCS, and ADMA) and the frequency of atrial fibrillation events. | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To evaluate the relationship between proteinbound uremic toxins (PBUTs) and atrial fibrillation rates. PBUTs such indoxyl sulfate (IS) and p-Cresol. sulfate (PCS) can induce atrial fibrillation |
| Total number of hypokalemic events defined as Piccolo POCT or laboratory-measured K+ of < 3.5 mEq/L. | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To evaluate whether the use of oral sodium zirconium cyclosilicate (Lokelmaâ) during periods when patients are receiving a 3.0 K+ /2.5 Ca++ dialysate bath is associated with hypokalemic events defined as K+ \<3.5 mEq/L. |
| Correlation between electrolyte levels and clinical events (intradialytic hypotension, muscle cramping, and cardiac events). Correlation between electrolytes falling below threshold levels | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To determine whether the levels of K+, Mg++, calcium and PO4 (measured promptly prior to the termination of dialysis) correlate with the incidence of clinical events, including intradialytic hypotension, muscle cramping, and cardiac events (defined as atrial fibrillation, bradycardia, ventricular tachycardia, and asystole). We will also evaluate whether the 3.0 K+ dialysate reduces the rates of these clinical events. |
| Number of events (measured promptly prior to the termination of dialysis) where a Piccolo POCT measurement of K+ is < 3.5 mEq/L OR Ca++ is < 7.0 mEq/L, OR Mg++ is < 2.0 mg/dl, OR a PO4 level is <3.0 mEq/L | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To determine the levels of K+ , Mg++, calcium and PO4 during dialysis (measured promptly prior to the termination of dialysis) during experimental treatment compared to standard treatment. |
| Frequencies of AEs, SAEs, and withdrawals due to AEs, with focus on treatment-related events. | 8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods | To evaluate the safety and tolerability of the experimental treatment compared to standard treatment based on the frequency of reported adverse experiences. |
Countries
United States
Outcome results
None listed