A Prospective, Randomized, Open-Label, Cross-Over Study of Lokelma to Control Interdialytic Hyperkalemia

NCT05535920 | Completed Phase 4 FDA Drug

• 1 other identifier: NN-007
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 5

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

Conditions

Hyperkalemia

Outcome Measures

Primary Outcomes (1)

• The change in atrial Fibrillation events

  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.

  8-week Treatment Phase-1 and the 8-week Treatment Phase-2 dialysate cross-over periods

Secondary Outcomes (2)

• 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

• 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

Other Outcomes (5)

• 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

• 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

• 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

Study Arms (2)

Rate Atrial fibrillation - 2.0K+ dialysate bath wo/ Lokelma to crossover

OTHER

Sequence A: standard 2.0 K+/2.5 Ca++ dialysate with no Lokelma supplementation for two (2) months, followed by a cross-over to experimental 3.0 K+/2.5 Ca++ dialysate with 5 grams powder oral suspension Lokelma supplementation (on off-dialysis days) for two (2) months. Each two-month treatment period (both 2.0 K+/2.5 Ca++ dialysate and 3.0 K+/2.5 Ca++ dialysate with Lokelma sequences) will be preceded by a two-week run-in period, to allow the patient to adapt to the new dialysate bath. While receiving the higher K+ dialysate, patient will be treated on off-dialysis days (4 days/week) with Lokelma, titrated to maintain K+ between 4.0 and 5.5 mEq/L. Refer to section 7.2 for the initial dose and frequency details.

Drug: LOKELMA 5 GM Powder for Oral Suspension

Rate Atrial fibrillation - 3.0K+ dialysate bath w/ 5 grams Lokelma to crossover

OTHER

• Sequence B: experimental 3.0 K+/2.5 Ca++ dialysate with 5 grams Lokelma supplementation (on off-dialysis days) for two (2) months, followed by standard 2.0 K+/2.5 Ca++ dialysate with no Lokelma supplementation for two (2) months. Each two-month treatment period (both 2.0 K+/2.5 Ca++ dialysate and 3.0 K+/2.5 Ca++ dialysate with Lokelma sequences) will be preceded by a two-week run-in period, to allow the patient to adapt to the new dialysate bath. While receiving the higher K+ dialysate, patient will be treated on off-dialysis days (4 days/week) with Lokelma, titrated to maintain K+ between 4.0 and 5.5 mEq/L. Refer to section 7.2 for the initial dose and frequency details.

Drug: LOKELMA 5 GM Powder for Oral Suspension

Interventions

LOKELMA 5 GM Powder for Oral Suspension DRUG

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.

Rate Atrial fibrillation - 2.0K+ dialysate bath wo/ Lokelma to crossover; Rate Atrial fibrillation - 3.0K+ dialysate bath w/ 5 grams Lokelma to crossover

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients with a QTc(f) \> 550 msec and/or Congenital long QT syndrome
• Patients with a Haemoglobin \< 9 g/dl.
• Patients with any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or Sponsor may pose a safety risk to a subject in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation.
• Patient receiving peritoneal or home hemodialysis
• Patient receiving hemodialysis via a tunneled inferior vena cava (IVC) catheter and known central stenosis of access extremity
• Patient receiving outpatient hemodialysis for \< 3 months
• Patient receiving outpatient hemodialysis for prolonged Acute Kidney Injury (AKI) and considered by the site Principal Investigator (PI) likely to achieve renal recovery within 6 months Note: Patients receiving out-patient hemodialysis for AKI for longer than 6 months with no demonstrable renal clearance can be screened for study participation.
• Patient currently receiving a 1.0 K+, 3.0 K+ dialysate bath and unwilling to convert to a 2.0 K+/2.5 Ca++ dialysate bath
• Subject unwilling to convert from a 2.0 K+ dialysate bath to a 3.0 K+ dialysate bath
• Two or more pre-dialysis K+ of \< 5.1 or \> 6.5 mEq/L measured by Piccolo POCT after the long dialytic "weekends" during screening Note: If one of the two screening pre-dialysis K+ levels is between 4.6 to 5.0 mEq/L or 6.6 to 7.0 mEq/L, the patient can undergo an additional whole blood Piccolo POCT K+ measurement. Patients who fail the third whole blood Piccolo POCT K+ measurement will be considered ineligible for study participation. Note: Screen failures can be re-screened once to confirm eligibility in the study.
• Any documented whole blood Piccolo POCT K+ measurement that falls below 4.6 mEq/L or exceeds 7.0 mEq/l during the screening period
• Current use of a medication for treatment of hyperkalemia (e.g., Patiromer).
• Anticipated life expectancy of 3 months duration
• Development of atrial fibrillation requiring hospitalization, medical therapy, anticoagulation, or cardioversion during study pre-screening or screening period
• Patient with a known placement of a dual or single chamber pacemaker

Sponsors & Collaborators

• NephroNet, Inc.: lead
• AstraZeneca: collaborator

Study Sites (5)

Balboa Research

La Jolla, California, 92024, United States

Location

Georgia Nephrology DBA Georgia Nephrology Research Institute

Lawrenceville, Georgia, 30046, United States

Location

Nephrology Associates of Northern Illinois and Indiana (NANI)

Fort Wayne, Indiana, 46804, United States

Location

Clinical Research Consultants

Kansas City, Missouri, 64111, United States

Location

Mountain Kidney & Hypertension Associates

Asheville, North Carolina, 28801, United States

Location

MeSH Terms

Conditions

Hyperkalemia

Interventions

Suspensions

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• James Tumlin, MD

  NephroNet, Inc.

  PRINCIPAL INVESTIGATOR

• Jeremy Whitson, BS

  NephroNet, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: September 10, 2022
• Study Start: April 14, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: June 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)