Acid-Base Composition With Use of hemoDialysates

Study Overview
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Brief Summary
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This study is a prospective, single center, single blind (patient and laboratory), randomized, cross-over, two week investigation of intradialytic acid-base kinetics and physiology associated with use of two commercial acid dialysate concentrates in prevalent hemodialysis patients.

Detailed Description
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Approximately 10-20 prevalent hemodialysis patients will be recruited. Subjects will randomized to receive one weekly hemodialysis treatment using each of the two acetate acid dialysate buffers of NaturaLyte and GranuFlo, which will be assigned in a random fashion. Acetate and bicarbonate concentrations will be assessed before, at eight time points during, and six time points after the completion of hemodialysis.

Official Title
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Acid-Base Composition With Use of hemoDialysates: the ABChD Trial

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Device: Group 1: GranuFlo
* Device: Group 2: NaturaLyte


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects eligible to be entered into this study will meet all of the following criteria: Adult female or male patients; age ≥18 years. End stage renal disease (ESRD) patients treated for >90 days with the modality of maintenance hemodialysis and on a stable dialysis prescription for the prior month. Patients utilizing a hemodialysis vascular access of a functioning arteriovenous fistula (AVF) or graft (AVG) during the prior month. The patient's AVF/AVG must be considered in stable functioning condition and not be expected to require any surgical revision/intervention during participation in the trial. Patients with an average spKt/V of ≥1.2 during 30 days prior to screening as determined by historic monthly laboratory adequacy measurements; for patients with only one available spKt/V an average will not be performed. (Note: spKt/V should not be captured from dialysis machine adequacy measurements.) Screening hemoglobin level of ≥9 g/dL, and investigator considers hemoglobin levels to have been clinically stable for at least 30 days. A sodium bicarbonate basic dialysate prescription that has not had any changes for 30 days prior to randomization, and is anticipated to be unchanged during study participation as determined by the investigator. Unchanged heparin dosing regimen for the past 30 days prior to randomization and anticipated unchanged heparin dosing during participation in this clinical trial. No changes two weeks prior to randomization or anticipated changes throughout the study in any phosphate binders, calcium supplements, anticoagulant therapies that are not used for hemodialysis treatment (e.g. warfarin, dabigatran, apixaban, rivaroxaban and acetylsalicylic acid (ASA)), non-dialysate sodium bicarbonate and/or citrate based concomitant medications. If treated with systemic glucocorticoid/corticosteroid medications, no dose changes in the previous two months before randomization, or anticipated dose changes throughout the study duration; the dosing regimen should be consistent with maintenance therapy (i.e. not for an acute or active uncontrolled disease) as determined by the investigator. (Note: this criteria does not pertain to inhaled and/or topical glucocorticoid/corticosteroid therapies) During the two weeks prior to screening, an average of no more than 3.5 kg in pre-dialysis weight gain. In the event greater than 3.5 kg is noted, the investigator will discuss the specific medical history with the Medical Monitor prior to enrollment. Willing to comply with all study procedures and be available for the duration of the study. Exclusion Criteria: Patients that meet any of the following criteria will be ineligible for this study: Patients unable to provide a signed and dated informed consent for this clinical research study. Pregnant or lactating female patients. Females of reproductive potential who do not agree to use a highly effective method of contraception, as determined by the investigator. Missed a scheduled outpatient dialysis treatment within two weeks prior to screening or anticipated to not attend any prescribed hemodialysis treatments during participation in the study. Screening or historic laboratory values of aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels ≥ 2 times the upper limit of normal. These blood laboratory tests must have been performed within 30 days prior to screening or prior to randomization. A screening or historic laboratory value of total bilirubin >1.9 mg/dL that was collected within 30 days prior to screening or obtained before randomization. Uncontrolled clinically significant blood pressure as determined by the investigator within 30 days prior to screening. Active or recent bleeding disorder within the past 30 days. Screening or historic platelet count <100,000 platelets per microliter (mcL) that was collected within 30 days prior to screening or before randomization. Chronic supplemental oxygen use within 30 days prior to randomization. Current active and significant chronic obstructive pulmonary disease (COPD) as determined by the investigator. Significant residual renal function as determined by the investigator. If the amount of residual renal function is in doubt, a 24 hour urine will be collected during the clinic admission to confirm the creatinine clearance. Decisions will be made after the results have been obtained as to the inclusion of data for these subjects. Active malignancy or a malignancy within the past five years, with exceptions for basal and squamous cell carcinoma. Active and clinically uncontrolled autoimmune disease as determined by the investigator. Subjects with controlled autoimmune diseases must be considered to be clinically stable in the opinion of the investigator (e.g. subjects with systemic lupus erythematosus (SLE) and no recent flares are not excluded). The investigator will consult with the referring physician if it is necessary to confirm the stability of an autoimmune disease. Diagnosed with human immunodeficiency virus (HIV). Diagnosed with congestive heart failure (CHF) class III or IV as classified by the New York Heart Association (NYHA) (refer to Appendix A) within the past 60 days. Planned or anticipated need for any surgical procedures during participation in the study. Current or recent illicit drug use or alcohol abuse as determined by the investigator. Subjects that have any significant medical condition as determined by the investigator, which make her/him ineligible for the study (e.g. clinically significant vomiting on dialysis which affects acid-base status). Any condition as determined by the investigator that would place the subject at an increased risk, or preclude the subject's full compliance with the study procedures and visits. Treatment with an investigational drug, device or intervention within 30 days prior to and during participation in this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: GranuFlo<br>Study subjects will be randomized to undergo dialysis treatments using GranuFlo, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using acid dialysate concentrations of NaturaLyte for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments. | Device: Group 1: GranuFlo<br>* Study subjects will be randomized to undergo dialysis treatments using GranuFlo, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using NaturaLyte, a commercially available acid dialysate concentration for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments.<br>* Other names: GranuFlo 45X;|
| Active Comparator: Group 2: NaturaLyte<br>Study subjects will be randomized to undergo dialysis treatments using NaturaLyte, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using acid dialysate concentrations of GranuFlo for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments. | Device: Group 2: NaturaLyte<br>* Study subjects will be randomized to undergo dialysis treatments using NaturaLyte, a commercially available acid dialysate concentrations for one weekly hemodialysis treatment. This will be followed by dialysis treatments using GranuFlo, a commercially available acid dialysate concentration for a second weekly hemodialysis treatment. Intervention: blood and dialysate samples will be obtained at specific time points during the dialysis treatments.<br>* Other names: NaturaLyte 45X;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peridialytic Arterialized Blood Bicarbonate Concentrations | Quantification of Peridialytic Arterialized Blood Bicarbonate Concentrations | Immediately prior to initiation of hemodialysis, and 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis and 15, 30, 45, 60, 75, and 90 minutes post hemodialysis | 
| Peridialytic Venous Blood Bicarbonate Concentrations | Quantification of Peridialytic Venous Blood Bicarbonate Concentrations | 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis | 
| Peridialytic Arterialized Blood Acetate Concentrations | Quantification of Peridialytic Arterialized Blood Acetate Concentrations | Immediately prior to initiation of hemodialysis, and 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis and 15, 30, 45, 60, 75, and 90 minutes post hemodialysis | 
| Peridialytic Venous Blood Acetate Concentrations | Quantification of Peridialytic Venous Blood Acetate Concentrations | 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis |