Kidney Failure
Conditions
Keywords
Soluble Ferric Pyrophosphate,, Pharmacokinetics,, Iron, Mass Transfer,, Hemodialysis, chronic therapy;
Brief summary
The purpose of this study is to determine the quantity of iron derived from SFP that is transferred from the dialysate to patients during a single dialysis session. The effects of various conditions which may affect the transfer of iron such as blood and dialysate flow rate, changes in bicarbonate delivery, dialyzer membrane type and the effect of reuse will also be investigated. The absorption and removal of iron from the blood will also be investigated.
Detailed description
* A total of 12 subjects on standard 3X/week hemodialysis will be studied in 2 groups (6 subjects per group) * 2 primary dialyzer membranes will be studied.: * Polyamide Membrane (Gambro Polyflux series: 17R and 21R) * Cellulose Triacetate (Baxter CT series: CT-190) * Each 1-week treatment cycle will include 3 haemodialysis (HD) sessions per subject, including 2 study treatment-HD sessions and 1 non-treatment-HD session per subject. Treatment-HD sessions will be conducted midweek and end-of-week (i.e. Dialysis days 3 and 5 of each week with a 1 day interdialytic interval) to avoid excessive fluid shifts due to the increased UF needed during the non-treatment HD session (conducted at beginning of the week; HD day 1). * Within each group, each subject will be randomized to 1 of 6 treatment sequences. The treatments to be investigated are: Control; new dialyzer, reused dialyzer, low blood flow/dialysate flow, Low bicarbonate concentration and a different synthetic dialyzer membrane (PAES) * Blood for a complete serum iron profile over time will be obtained during the new dialyzer (SFP/standard bicarbonate/new dialyzer/ high Qb and Qd) for all subjects. This will necessitate approximately a 24-hour inpatient confinement to obtain blood at specified time intervals after dialysis is completed. Blood for a partial iron profile will be collected during the dialysis sessions at all other dialysis sessions. * Each of the 6 enrolled subjects per dialyzer membrane type will be assigned to a different sequence of treatments to help ensure that the treatment sequence does not affect the analysis (Note: the first dialysis sessions of each of the 3 study weeks, i.e. HD1, HD4 and HD7, are non-study related sessions during which no study procedures are performed except for adverse event collection. * Patients should not be receiving any of the following medications from screening through the end of the study: * Oral iron preparations, including multivitamin supplements containing iron * Intravenous iron preparations * Doses of ESA's should not be changed from screening to the end of the study.
Interventions
OTHERPlacebo
Sponsors
Rockwell Medical Technologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult subject ≥ 18 years of age undergoing chronic hemodialysis for chronic kidney disease (CKD) for at least 3 months, expected to remain on hemodialysis and be able to complete the study. 2. Screening Hgb ≥ 9.5 g/dL. 3. Screening transferrin saturation % (TSAT) ≥ 15% to ≤ 45%. 4. Screening serum ferritin ≥ 200 to ≤ 1200 µg/L. 5. Subject's standard dialyzer membrane is one of the 2 types, i.e. Baxter CT-190 or Gambro 17R or 21R. 6. The subject uses a reprocessed dialyzer for standard HD treatments. 7. Prescribed dialysis 3X/week. 8. Minimally adequate measured dialysis dose defined as URR (urea reduction ratio) ≥ 65%, or single-pool Kt/V (dialyzer clearance of urea multiplied by dialysis time, divided by patient's total body water) ≥ 1.2, or KIDt/V (online dialyzer clearance measured using ionic dialysance multiplied by dialysis time, divided by patients total body water) ≥ 1.2. 9. Stable dialyzer blood flow rate that is generally ≥ 350 mL/min and acceptable to the Investigator. 10. Stable dialysate flow rate that is generally ≥ 600 mL/min and acceptable to the Investigator. 11. Vascular access for dialysis that will be used upon enrollment with stable function in the judgment of the Investigator. 12. Female subjects must be either amenorrheic for ≥ 1 year or agree to not become pregnant by continuous use of an effective birth control method acceptable to the Investigator for the duration of their participation in the study. 13. Must be willing and able to provide written informed consent directly or through their authorized representative.
Exclusion criteria
1. Subject has a living kidney donor identified or living-donor kidney transplant scheduled during study participation. (Note: Patients awaiting deceased-donor transplant need not be excluded.) 2. Vascular access for hemodialysis is a femoral catheter. 3. Known active bleeding from any site other than AV fistula or graft (e.g., gastrointestinal, hemorrhoidal, nasal, pulmonary, etc.). 4. Scheduled surgery during the study. 5. RBC or whole blood transfusion within 4 weeks prior to Screening. 6. Hospitalization in the month prior to Screening (except for vascular access surgery) that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of this study. 7. Evidence of current malignancy involving a site other than skin (except any melanoma, which renders the patient non-eligible). 8. History of drug or alcohol abuse within the last 6 months. 9. Regularly requiring hemodialysis more than three times per week. 10. Noncompliance with dialysis regimen in the opinion of the Investigator. 11. Pregnancy or intention to become pregnant before completing all study drug treatment. 12. Known ongoing inflammatory disorder (other than CKD), such as systemic lupus erythematosus, rheumatoid arthritis, or other collagen-vascular disease undergoing a disease flare. 13. Any current febrile illness (e.g., oral temperature \> 100.4°F, 38°C). (The patient may subsequently become eligible at least 1 week after resolution of the illness). 14. Known active bacterial, tuberculosis, fungal, viral, or parasitic infection requiring anti-microbial therapy or anticipated to require anti-microbial therapy during the patient's participation in this study. 15. Occult tuberculosis requiring prophylactic treatment with anti-tubercular drug(s) that overlaps with the patient's participation in this study. 16. Known positive status for hepatitis B surface antigen (hepatitis B testing is not required as part of this protocol). 17. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this protocol). 18. Cirrhosis of the liver based on histological criteria or clinical criteria (i.e., presence of ascites, esophageal varices, multiple spider nevi, or history of hepatic encephalopathy). 19. Active hepatitis with ALT and/or AST levels consistently greater than twice the upper limit of normal at any time during the two months prior to enrollment. 20. Participation in a study of an investigational drug or device within 30 days prior to randomization in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Net Iron Delivery From SFP Via the Dialysate | one dialysis session (approximately 4 hours) | To measure the SFP-derived total iron from the reference HD (Treatment B: SFP, new membrane, high Qb/Qd, 37 mEq bicarbonate). Expended dialysate over the intervals of 0.5, 1, 2 ,3 and 4 hours will be collected and measured. Aliquots will be analyzed for iron content. The mean cumulative net iron delivery will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD | one dialysis session (approximately 4 hours) | To compare the amount of SFP-derived iron administered under various treatment conditions to the reference HD (Treatment B: SFP, new membrane, high Qb/Qd, 37 mEq bicarbonate): Dialyzer reuse, Low machine bicarbonate delivery, Polyarylethersulfone (PAES) membrane, and Low Qb/Qd.Iron concentration in timed dialysate collections will be analyzed. Expended dialysate over the intervals of 0.5, 1, 2 ,3 and 4 hours will be collected and measured. Aliquots will be analyzed for iron content. The mean cumulative net iron delivery will be reported. |
| Pharmacokinetics of Serum Iron and Exploratory Modeling | one dialysis session (approximately 4 hours) | The serum Total Iron, Transferrin Bound Iron (TBI) and Non-transferrin Bound Iron (NTBI) pharmacokinetic parameters (baseline corrected and total) will be listed and summarized for each membrane group and overall. The mean serum total iron, TBI, NTBI, unsaturation iron binding capacity (UIBC) and total iron binding capacity (TIBC) concentrations at baseline (BL), end-of-treatment, and the change from BL will be listed for each group (Baxter and Gambro Polyflux), measured from the reference HD (Treatment B: SFP, new membrane, high Qb/Qd, 37 mEq bicarbonate). |
| Dialysate InFlow Iron Concentration | 4 hours | Dialysate inflow iron concentration was calculated for each treatment group at t = 0, 0.5, 1, 2, 3, and 4 hours. |
| Dialysate OutFlow Iron Concentration | 4 hours | Dialysate outflow iron concentration was calculated for each treatment group at t = 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, and 4 hours. |
Countries
United States
Participant flow
Recruitment details
19 patients were screened and 12 total patients were enrolled. Each patient participated in each of the 6 treatment periods.
Participants by arm
| Arm | Count |
|---|---|
| Baxter CT-190 (Group 1: Cellulose Triacetate Membrane) Enrolled subjects were assigned to 1 of 2 groups based on the type of dialyzer membrane used by each subject at Screening: Baxter CT-190 (Group 1; N = 6; cellulose triacetate membrane) or Gambro 17R/21R (Group 2; N = 6; polyamide membrane). Within each dialyzer membrane group, each subject received one control treatment and 5 treatments with SFP added to dialysate. | 6 |
| Gambro 17R/21R (Group 2: Polyamide Membrane). Enrolled subjects were assigned to 1 of 2 groups based on the type of dialyzer membrane used by each subject at Screening: Baxter CT-190 (Group 1; N = 6; cellulose triacetate membrane) or Gambro 17R/21R (Group 2; N = 6; polyamide membrane). Within each dialyzer membrane group, each subject received one control treatment and 5 treatments with SFP added to dialysate. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Baxter CT-190 (Group 1: Cellulose Triacetate Membrane) | Gambro 17R/21R (Group 2: Polyamide Membrane). | Total |
|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 14.73 | 52.8 years STANDARD_DEVIATION 8.89 | 52.3 years STANDARD_DEVIATION 11.61 |
| BMI | 26.425 kg/m^2 STANDARD_DEVIATION 6.1611 | 28.332 kg/m^2 STANDARD_DEVIATION 6.6425 | 27.378 kg/m^2 STANDARD_DEVIATION 6.1888 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 2 / 12 | 2 / 12 | 1 / 12 | 2 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Net Iron Delivery From SFP Via the Dialysate
To measure the SFP-derived total iron from the reference HD (Treatment B: SFP, new membrane, high Qb/Qd, 37 mEq bicarbonate). Expended dialysate over the intervals of 0.5, 1, 2 ,3 and 4 hours will be collected and measured. Aliquots will be analyzed for iron content. The mean cumulative net iron delivery will be reported.
Time frame: one dialysis session (approximately 4 hours)
Population: For this preliminary and explorative study, no prospective calculations of statistical power were made; statistics were descriptive only. All subjects were included in the calculation of all study outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Net Iron Delivery From SFP Via the Dialysate | 692 microgram | Standard Deviation 1010 |
Secondary
Dialysate InFlow Iron Concentration
Dialysate inflow iron concentration was calculated for each treatment group at t = 0, 0.5, 1, 2, 3, and 4 hours.
Time frame: 4 hours
Population: For this preliminary and explorative study, no prospective calculations of statistical power were made; statistics were descriptive only. All subjects were included in the calculation of all study outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Dialysate InFlow Iron Concentration | t = 0 hours | 12.5 micrograms/L | Standard Deviation 43.3 |
| Control | Dialysate InFlow Iron Concentration | t = 0.5 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate InFlow Iron Concentration | t = 1 hour | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate InFlow Iron Concentration | t = 2 hours | 0.925 micrograms/L | Standard Deviation 3.2 |
| Control | Dialysate InFlow Iron Concentration | t = 3 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate InFlow Iron Concentration | t = 4 hours | 0 micrograms/L | Standard Deviation 0 |
| Treatment B | Dialysate InFlow Iron Concentration | t = 4 hours | 73.6 micrograms/L | Standard Deviation 3.4 |
| Treatment B | Dialysate InFlow Iron Concentration | t = 1 hour | 74 micrograms/L | Standard Deviation 2.53 |
| Treatment B | Dialysate InFlow Iron Concentration | t = 0.5 hours | 71 micrograms/L | Standard Deviation 6.87 |
| Treatment B | Dialysate InFlow Iron Concentration | t = 2 hours | 74.4 micrograms/L | Standard Deviation 2.66 |
| Treatment B | Dialysate InFlow Iron Concentration | t = 3 hours | 71.9 micrograms/L | Standard Deviation 6.98 |
| Treatment B | Dialysate InFlow Iron Concentration | t = 0 hours | 0 micrograms/L | Standard Deviation 0 |
| Treatment C | Dialysate InFlow Iron Concentration | t = 4 hours | 73.3 micrograms/L | Standard Deviation 5.74 |
| Treatment C | Dialysate InFlow Iron Concentration | t = 2 hours | 75.9 micrograms/L | Standard Deviation 7.73 |
| Treatment C | Dialysate InFlow Iron Concentration | t = 0.5 hours | 74.1 micrograms/L | Standard Deviation 9.44 |
| Treatment C | Dialysate InFlow Iron Concentration | t = 1 hour | 76.3 micrograms/L | Standard Deviation 7.46 |
| Treatment C | Dialysate InFlow Iron Concentration | t = 3 hours | 76.8 micrograms/L | Standard Deviation 8.75 |
| Treatment C | Dialysate InFlow Iron Concentration | t = 0 hours | 0 micrograms/L | Standard Deviation 0 |
| Treatment D | Dialysate InFlow Iron Concentration | t = 4 hours | 63.7 micrograms/L | Standard Deviation 6.64 |
| Treatment D | Dialysate InFlow Iron Concentration | t = 3 hours | 64.8 micrograms/L | Standard Deviation 5.84 |
| Treatment D | Dialysate InFlow Iron Concentration | t = 0.5 hours | 63.3 micrograms/L | Standard Deviation 5.5 |
| Treatment D | Dialysate InFlow Iron Concentration | t = 1 hour | 63.9 micrograms/L | Standard Deviation 5.12 |
| Treatment D | Dialysate InFlow Iron Concentration | t = 2 hours | 64.4 micrograms/L | Standard Deviation 5.37 |
| Treatment D | Dialysate InFlow Iron Concentration | t = 0 hours | 1.9 micrograms/L | Standard Deviation 6.58 |
| Treatment E | Dialysate InFlow Iron Concentration | t = 3 hours | 57.7 micrograms/L | Standard Deviation 8.36 |
| Treatment E | Dialysate InFlow Iron Concentration | t = 4 hours | 56.1 micrograms/L | Standard Deviation 4.8 |
| Treatment E | Dialysate InFlow Iron Concentration | t = 0.5 hours | 54.7 micrograms/L | Standard Deviation 4.61 |
| Treatment E | Dialysate InFlow Iron Concentration | t = 1 hour | 56.6 micrograms/L | Standard Deviation 5.32 |
| Treatment E | Dialysate InFlow Iron Concentration | t = 2 hours | 58.2 micrograms/L | Standard Deviation 7.57 |
| Treatment E | Dialysate InFlow Iron Concentration | t = 0 hours | 0 micrograms/L | Standard Deviation 0 |
| Treatment F | Dialysate InFlow Iron Concentration | t = 1 hour | 69.2 micrograms/L | Standard Deviation 13.3 |
| Treatment F | Dialysate InFlow Iron Concentration | t = 0 hours | 0 micrograms/L | Standard Deviation 0 |
| Treatment F | Dialysate InFlow Iron Concentration | t = 0.5 hours | 64.4 micrograms/L | Standard Deviation 14 |
| Treatment F | Dialysate InFlow Iron Concentration | t = 4 hours | 69.3 micrograms/L | Standard Deviation 14.6 |
| Treatment F | Dialysate InFlow Iron Concentration | t = 2 hours | 68.5 micrograms/L | Standard Deviation 14 |
| Treatment F | Dialysate InFlow Iron Concentration | t = 3 hours | 69.1 micrograms/L | Standard Deviation 12.2 |
Secondary
Dialysate OutFlow Iron Concentration
Dialysate outflow iron concentration was calculated for each treatment group at t = 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, and 4 hours.
Time frame: 4 hours
Population: For this preliminary and explorative study, no prospective calculations of statistical power were made; statistics were descriptive only. All subjects were included in the calculation of all study outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Dialysate OutFlow Iron Concentration | t = 3.5 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate OutFlow Iron Concentration | t = 1 hour | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate OutFlow Iron Concentration | t = 0.75 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate OutFlow Iron Concentration | t = 3 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate OutFlow Iron Concentration | t = 4 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate OutFlow Iron Concentration | t = 2.5 hours | 1.74 micrograms/L | Standard Deviation 6.03 |
| Control | Dialysate OutFlow Iron Concentration | t = 0.25 hours | 0.643 micrograms/L | Standard Deviation 2.23 |
| Control | Dialysate OutFlow Iron Concentration | t = 2 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate OutFlow Iron Concentration | t = 1.5 hours | 0 micrograms/L | Standard Deviation 0 |
| Control | Dialysate OutFlow Iron Concentration | t = 0.5 hours | 3.21 micrograms/L | Standard Deviation 11.1 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 1.5 hours | 74.2 micrograms/L | Standard Deviation 5.04 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 2 hours | 70.9 micrograms/L | Standard Deviation 8.56 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 0.75 hours | 81.8 micrograms/L | Standard Deviation 25.9 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 0.5 hours | 68.4 micrograms/L | Standard Deviation 8.22 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 3 hours | 77.9 micrograms/L | Standard Deviation 17.8 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 0.25 hours | 68.6 micrograms/L | Standard Deviation 8.15 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 2.5 hours | 70.6 micrograms/L | Standard Deviation 8.26 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 1 hour | 64.4 micrograms/L | Standard Deviation 22.1 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 4 hours | 72.4 micrograms/L | Standard Deviation 6.03 |
| Treatment B | Dialysate OutFlow Iron Concentration | t = 3.5 hours | 74 micrograms/L | Standard Deviation 10.5 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 0.25 hours | 73.1 micrograms/L | Standard Deviation 11.2 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 3.5 hours | 71.6 micrograms/L | Standard Deviation 13.7 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 4 hours | 76.5 micrograms/L | Standard Deviation 13.1 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 0.5 hours | 74.1 micrograms/L | Standard Deviation 11.1 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 0.75 hours | 74.9 micrograms/L | Standard Deviation 11.6 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 1 hour | 74.1 micrograms/L | Standard Deviation 13.3 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 1.5 hours | 73.6 micrograms/L | Standard Deviation 12.6 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 2 hours | 71.9 micrograms/L | Standard Deviation 17.4 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 2.5 hours | 75 micrograms/L | Standard Deviation 15 |
| Treatment C | Dialysate OutFlow Iron Concentration | t = 3 hours | 75.6 micrograms/L | Standard Deviation 10.4 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 0.5 hours | 62.2 micrograms/L | Standard Deviation 7.62 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 3.5 hours | 56.5 micrograms/L | Standard Deviation 3.1 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 1 hour | 61.6 micrograms/L | Standard Deviation 9.1 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 0.25 hours | 61.8 micrograms/L | Standard Deviation 6.7 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 1.5 hours | 61.8 micrograms/L | Standard Deviation 8.2 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 3 hours | 60.6 micrograms/L | Standard Deviation 7.21 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 2 hours | 63.4 micrograms/L | Standard Deviation 6.99 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 4 hours | 60.8 micrograms/L | Standard Deviation 8.81 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 2.5 hours | 58.1 micrograms/L | Standard Deviation 12 |
| Treatment D | Dialysate OutFlow Iron Concentration | t = 0.75 hours | 62 micrograms/L | Standard Deviation 8.61 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 1.5 hours | 53.8 micrograms/L | Standard Deviation 9.09 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 4 hours | 54.4 micrograms/L | Standard Deviation 9.08 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 0.5 hours | 54.3 micrograms/L | Standard Deviation 8.36 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 3.5 hours | 53.3 micrograms/L | Standard Deviation 4.75 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 2 hours | 57.2 micrograms/L | Standard Deviation 6.27 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 3 hours | 55.2 micrograms/L | Standard Deviation 8.42 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 0.75 hours | 50.4 micrograms/L | Standard Deviation 17.4 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 2.5 hours | 55.4 micrograms/L | Standard Deviation 7.65 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 1 hour | 53.5 micrograms/L | Standard Deviation 8.41 |
| Treatment E | Dialysate OutFlow Iron Concentration | t = 0.25 hours | 53 micrograms/L | Standard Deviation 7.16 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 1 hour | 68.5 micrograms/L | Standard Deviation 12.2 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 1.5 hours | 65.4 micrograms/L | Standard Deviation 9.44 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 0.25 hours | 66.2 micrograms/L | Standard Deviation 9.19 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 4 hours | 66.3 micrograms/L | Standard Deviation 12.6 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 0.5 hours | 65.6 micrograms/L | Standard Deviation 9.85 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 2.5 hours | 65.8 micrograms/L | Standard Deviation 10.7 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 3 hours | 64.3 micrograms/L | Standard Deviation 13.5 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 2 hours | 65.3 micrograms/L | Standard Deviation 10.8 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 0.75 hours | 64.8 micrograms/L | Standard Deviation 11.7 |
| Treatment F | Dialysate OutFlow Iron Concentration | t = 3.5 hours | 71.4 micrograms/L | Standard Deviation 8.62 |
Secondary
Pharmacokinetics of Serum Iron and Exploratory Modeling
The serum Total Iron, Transferrin Bound Iron (TBI) and Non-transferrin Bound Iron (NTBI) pharmacokinetic parameters (baseline corrected and total) will be listed and summarized for each membrane group and overall. The mean serum total iron, TBI, NTBI, unsaturation iron binding capacity (UIBC) and total iron binding capacity (TIBC) concentrations at baseline (BL), end-of-treatment, and the change from BL will be listed for each group (Baxter and Gambro Polyflux), measured from the reference HD (Treatment B: SFP, new membrane, high Qb/Qd, 37 mEq bicarbonate).
Time frame: one dialysis session (approximately 4 hours)
Population: For this preliminary and explorative study, no prospective calculations of statistical power were made; statistics were descriptive only. All subjects were included in the calculation of all study outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Pharmacokinetics of Serum Iron and Exploratory Modeling | End-of Treatment TIBC | 247.2 microgram/dL | Standard Deviation 39.83 |
| Control | Pharmacokinetics of Serum Iron and Exploratory Modeling | Baseline TIBC | 244.7 microgram/dL | Standard Deviation 49.31 |
| Control | Pharmacokinetics of Serum Iron and Exploratory Modeling | TIBC Change from BL to EoT | 2.5 microgram/dL | Standard Deviation 41.95 |
| Treatment B | Pharmacokinetics of Serum Iron and Exploratory Modeling | End-of Treatment TIBC | 233.5 microgram/dL | Standard Deviation 61.4 |
| Treatment B | Pharmacokinetics of Serum Iron and Exploratory Modeling | Baseline TIBC | 221.7 microgram/dL | Standard Deviation 52.88 |
| Treatment B | Pharmacokinetics of Serum Iron and Exploratory Modeling | TIBC Change from BL to EoT | 11.8 microgram/dL | Standard Deviation 14.5 |
| Treatment C | Pharmacokinetics of Serum Iron and Exploratory Modeling | Baseline TIBC | 233.2 microgram/dL | Standard Deviation 50.21 |
| Treatment C | Pharmacokinetics of Serum Iron and Exploratory Modeling | TIBC Change from BL to EoT | 7.2 microgram/dL | Standard Deviation 30.32 |
| Treatment C | Pharmacokinetics of Serum Iron and Exploratory Modeling | End-of Treatment TIBC | 240.3 microgram/dL | Standard Deviation 49.85 |
Secondary
To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD
To compare the amount of SFP-derived iron administered under various treatment conditions to the reference HD (Treatment B: SFP, new membrane, high Qb/Qd, 37 mEq bicarbonate): Dialyzer reuse, Low machine bicarbonate delivery, Polyarylethersulfone (PAES) membrane, and Low Qb/Qd.Iron concentration in timed dialysate collections will be analyzed. Expended dialysate over the intervals of 0.5, 1, 2 ,3 and 4 hours will be collected and measured. Aliquots will be analyzed for iron content. The mean cumulative net iron delivery will be reported.
Time frame: one dialysis session (approximately 4 hours)
Population: For this preliminary and explorative study, no prospective calculations of statistical power were made; statistics were descriptive only. All subjects were included in the calculation of all study outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD | -18.5 microgram | Standard Deviation 175 |
| Treatment B | To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD | 692 microgram | Standard Deviation 1010 |
| Treatment C | To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD | 578 microgram | Standard Deviation 1380 |
| Treatment D | To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD | 587 microgram | Standard Deviation 994 |
| Treatment E | To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD | 130 microgram | Standard Deviation 594 |
| Treatment F | To Compare the Amount of SFP-derived Iron Administered Under Various Treatment Conditions to the Reference HD | 350 microgram | Standard Deviation 1940 |