A Prospective, Randomized, Multi-Center, Open-Label, Cross-Over Study of Lokelma to Control Interdialytic Hyperkalemia Following Augmentation of Dialysate Potassium
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 5
- 主要终点
- The change in atrial Fibrillation events
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Rate Atrial fibrillation - 2.0K+ dialysate bath wo/ Lokelma to crossover
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.
干预措施: LOKELMA 5 GM Powder for Oral Suspension (Drug)
Rate Atrial fibrillation - 3.0K+ dialysate bath w/ 5 grams Lokelma to crossover
• 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.
干预措施: LOKELMA 5 GM Powder for Oral Suspension (Drug)
结局指标
主要结局
The change in atrial Fibrillation events
时间窗: 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.
次要结局
- 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)