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

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NephroNet, Inc.
• Collaborator: AstraZeneca

Criteria

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:

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Exclusion Criteria Related to the Underlying Condition:

• 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).

• Note: If a medication for treatment of hyperkalemia is stopped prior to or after the consenting process, the subject will undergo a one week washout prior to the first whole blood Piccolo POCT K+ measurement. Exclusion Criteria Related to Other Medical Conditions and Treatments:

• 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

• Patient with an automatic implantable cardiac defibrillator (AICD)

• Patient with a LINQ implanted cardiac loop recorder with less than 6 months of battery life.

• Current use of amiodarone or other anti-arrhythmic therapy. Note: Patients on such medications must undergo a two week washout prior to the first whole blood Piccolo POCT K+ measurement.

• Known history of cardiac arrhythmias due to prolonged QT syndrome

• Subject unwilling to receive an implanted LINQ cardiac loop recorder (unless 6 months are remaining in their previously implanted device).

• Known active drug abuse

• Positive hepatitis C polymerase chain reaction (PCR) test with active viral deoxyribonucleic acid (DNA) shedding or chronic active hepatitis B as evidenced by detectable surface antigen from standard of care routine dialysis labs. Note: Patients with negative PCR DNA testing for either hepatitis B or C will be allowed to participate in the study.

• Known to have tested positive for human immunodeficiency virus (HIV) from standard of care routine dialysis labs.

• For women only: currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

• Patients with known and/or active severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders or diabetic gastroparesis Exclusion Criteria Related to the Investigational Product (IP):

• Known hypersensitivity to sodium zirconium cyclosilicate (Lokelmaâ).

Other/General Exclusion Criteria:

• Previous randomization in the present study. Note: Screen failures can be re-screened once to confirm eligibility in the study.

• Participation in another interventional (non-observational) clinical study within 4 weeks prior to enrollment in the present study