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

NephroNet, Inc.

Status and phase: Completed; Phase 4

Conditions: Hyperkalemia

Treatments: Drug: LOKELMA 5 GM Powder for Oral Suspension

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05535920

NN-007

Details and patient eligibility

About

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

Full 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.

Enrollment: 88 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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88 participants in 2 patient groups

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

Other group

Description:

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.

Treatment:

Drug: LOKELMA 5 GM Powder for Oral Suspension

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

Other group

Description:

• 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.

Treatment:

Drug: LOKELMA 5 GM Powder for Oral Suspension