Acid-Base Composition With Use of hemoDialysates (ABChD)

• ClinicalTrials.gov Identifier: NCT02334267
• Recruitment Status: Completed
• First Posted: January 8, 2015
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Sponsor: Fresenius Medical Care North America
• Information provided by (Responsible Party): Fresenius Medical Care North America

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
End Stage Renal Disease	Device: Group 1: GranuFlo; Device: Group 2: NaturaLyte	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Acid-Base Composition With Use of hemoDialysates: the ABChD Trial
• Study Start Date: November 2014
• Actual Primary Completion Date: February 2015
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group 1: GranuFlo; 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; 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.; Other Name: GranuFlo 45X
Active Comparator: Group 2: NaturaLyte; 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; 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.; Other Name: NaturaLyte 45X

Outcome Measures

Primary Outcome Measures :

1. Peridialytic Arterialized Blood Bicarbonate Concentrations [ Time Frame: 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 ]
   Quantification of Peridialytic Arterialized Blood Bicarbonate Concentrations
2. Peridialytic Venous Blood Bicarbonate Concentrations [ Time Frame: 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis ]
   Quantification of Peridialytic Venous Blood Bicarbonate Concentrations
3. Peridialytic Arterialized Blood Acetate Concentrations [ Time Frame: 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 ]
   Quantification of Peridialytic Arterialized Blood Acetate Concentrations
4. Peridialytic Venous Blood Acetate Concentrations [ Time Frame: 25, 60, 90, 120, 150, 180, 210, 240 minutes of hemodialysis ]
   Quantification of Peridialytic Venous Blood Acetate Concentrations

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Subjects eligible to be entered into this study will meet all of the following criteria:

1. Adult female or male patients; age ≥18 years.
2. 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.
3. 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.
4. 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.)
5. Screening hemoglobin level of ≥9 g/dL, and investigator considers hemoglobin levels to have been clinically stable for at least 30 days.
6. 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.
7. Unchanged heparin dosing regimen for the past 30 days prior to randomization and anticipated unchanged heparin dosing during participation in this clinical trial.
8. 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.
9. 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)
10. 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.
11. 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:

1. Patients unable to provide a signed and dated informed consent for this clinical research study.
2. Pregnant or lactating female patients.
3. Females of reproductive potential who do not agree to use a highly effective method of contraception, as determined by the investigator.
4. 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.
5. 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.
6. 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.
7. Uncontrolled clinically significant blood pressure as determined by the investigator within 30 days prior to screening.
8. Active or recent bleeding disorder within the past 30 days.
9. Screening or historic platelet count <100,000 platelets per microliter (mcL) that was collected within 30 days prior to screening or before randomization.
10. Chronic supplemental oxygen use within 30 days prior to randomization.
11. Current active and significant chronic obstructive pulmonary disease (COPD) as determined by the investigator.
12. 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.
13. Active malignancy or a malignancy within the past five years, with exceptions for basal and squamous cell carcinoma.
14. 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.
15. Diagnosed with human immunodeficiency virus (HIV).
16. 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.
17. Planned or anticipated need for any surgical procedures during participation in the study.
18. Current or recent illicit drug use or alcohol abuse as determined by the investigator.
19. 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).
20. 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.
21. Treatment with an investigational drug, device or intervention within 30 days prior to and during participation in this clinical trial.

Contacts and Locations

Locations

United States, Tennessee

Volunteer Research Group and New Orleans Center for Clinical Research

Knoxville, Tennessee, United States, 37920

Sponsors and Collaborators

Fresenius Medical Care North America

Investigators

• Principal Investigator: William B Smith, MD; Volunteer Research Group and New Orleans Center for Clinical Research

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Smith WB, Gibson S, Newman GE, Hendon KS, Askelson M, Zhao J, Hantash J, Flanagan B, Larkin JW, Usvyat LA, Thadhani RI, Maddux FW. The dynamics of the metabolism of acetate and bicarbonate associated with use of hemodialysates in the ABChD trial: a phase IV, prospective, single center, single blind, randomized, cross-over, two week investigation. BMC Nephrol. 2017 Aug 29;18(1):273. doi: 10.1186/s12882-017-0683-6.

• Responsible Party: Fresenius Medical Care North America
• ClinicalTrials.gov Identifier: NCT02334267
• Other Study ID Numbers: ABChD
• First Posted: January 8, 2015
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Kidney Failure, Chronic; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency