Quantitative Mass Transfer of SFP-iron From Dialysate to... | NCT01894906

NCT01894906

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Control	Placebo Comparator	Each subject will receive one control treatment and 5 treatments with SFP added to dialysate. The 5 SFP treatments will encompass 5 different conditions which may impact the intradialytic transfer of iron to the subject: new dialyzer, reused dialyzer, low blood/dialysate flow rate, low machine delivered bicarbonate concentration, and a different synthetic dialysis membrane (PAES).	Other: Placebo
Soluble Ferric Pyrophosphate	Experimental	Group/ cohort designation: Cellulose dialysis membrane (CT-190)/ Polyamide membrane. Each subject will receive one control treatment and 5 treatments with SFP added to dialysate. The 5 SFP treatments will encompass 5 different conditions which may impact the intradialytic transfer of iron to the subject: new dialyzer, reused dialyzer, low blood/dialysate flow rate, low machine delivered bicarbonate concentration, and a different synthetic dialysis membrane (PAES).	Drug: Soluble Ferric Pyrophosphate

Name	Type	Description	Arm Group Labels	Other Names
Soluble Ferric Pyrophosphate	Drug		Soluble Ferric Pyrophosphate	SFP
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	one dialysis session (approximately 4 hours)

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
Screening Hgb ≥ 9.5 g/dL.
Screening transferrin saturation % (TSAT) ≥ 15% to ≤ 45%.
Screening serum ferritin ≥ 200 to ≤ 1200 µg/L.
Subject's standard dialyzer membrane is one of the 2 types, i.e. Baxter CT-190 or Gambro 17R or 21R.
The subject uses a reprocessed dialyzer for standard HD treatments.
Prescribed dialysis 3X/week.
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.
Stable dialyzer blood flow rate that is generally ≥ 350 mL/min and acceptable to the Investigator.
Stable dialysate flow rate that is generally ≥ 600 mL/min and acceptable to the Investigator.
Vascular access for dialysis that will be used upon enrollment with stable function in the judgment of the Investigator.
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.
Must be willing and able to provide written informed consent directly or through their authorized representative.

Exclusion Criteria:

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.)
Vascular access for hemodialysis is a femoral catheter.
Known active bleeding from any site other than AV fistula or graft (e.g., gastrointestinal, hemorrhoidal, nasal, pulmonary, etc.).
Scheduled surgery during the study.
RBC or whole blood transfusion within 4 weeks prior to Screening.
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.
Evidence of current malignancy involving a site other than skin (except any melanoma, which renders the patient non-eligible).
History of drug or alcohol abuse within the last 6 months.
Regularly requiring hemodialysis more than three times per week.
Noncompliance with dialysis regimen in the opinion of the Investigator.
Pregnancy or intention to become pregnant before completing all study drug treatment.
Known ongoing inflammatory disorder (other than CKD), such as systemic lupus erythematosus, rheumatoid arthritis, or other collagen-vascular disease undergoing a disease flare.
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).
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.
Occult tuberculosis requiring prophylactic treatment with anti-tubercular drug(s) that overlaps with the patient's participation in this study.
Known positive status for hepatitis B surface antigen (hepatitis B testing is not required as part of this protocol).
Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this protocol).
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).
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.
Participation in a study of an investigational drug or device within 30 days prior to randomization in this study.

Name	Affiliation	Role
Raymond D Pratt, MC FACP	Rockwell Medical Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Minneapolis	Minnesota	55404	United States

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Mean

Standard Deviation

microgram

one dialysis session (approximately 4 hours)

ID	Title	Description
OG000	Control

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Control	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. Treatment A was one dialysis session without SFP added to the bicarbonate, with standard bicarbonate concentration, blood flow rate, dialysis flow rate, and new dialyzer.

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications