Title

Dose Ranging Study of Dialysate Containing Soluble Iron to Treat Subjects With End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis
A Dose Ranging Study of Dialysate Containing Soluble Ferric Pyrophosphate (SFP) Versus Control in Subjects With ESRD Receiving Chronic Hemodialysis.
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    bicarbonate ferric pyrophosphate citrate ...
  • Study Participants

    131
The purpose of this study is to determine whether Dialysate containing soluble iron (Soluble Ferric Pyrophosphate) is safe and effective in maintaining physiological iron levels during chronic hemodialysis.
The study was designed to evaluate the efficacy of SFP-containing dialysate solution in maintaining physiological iron levels during chronic hemodialysis, as measured by the primary endpoint of the percent of patients whose Hemoglobin (Hgb) decreased by at least 1.0 gram/ deciliter (g/dL) from baseline. The efficacy and safety findings are to be used to determine the optimal concentration of SFP needed to safely maintain iron levels, compensating for iron losses during chronic hemodialysis.
Study Started
Aug 31
2007
Primary Completion
Oct 31
2009
Study Completion
Jan 31
2010
Results Posted
Feb 08
2011
Estimate
Last Update
Dec 02
2020

Device Standard Bicarbonate Solution

Patients received 0 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.

  • Other names: Placebo

Drug Soluble Ferric Pyrophosphate

Patients received 5 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.

  • Other names: SFP

Drug Soluble Ferric Pyrophosphate

Patients received 10 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.

  • Other names: SFP

Drug Soluble Ferric Pyrophosphate

Patients received 12 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.

  • Other names: SFP

Drug Soluble Ferric Pyrophosphate

Patients received 15 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.

  • Other names: SFP

0 µg iron/dL of dialysate Placebo Comparator

Placebo 0 micrograms (µg) of iron/ deciliter (dL) of dialysate

5 µg iron/dL of dialysate Experimental

5 micrograms (µg) of iron/ deciliter (dL) of dialysate

10 µg iron/dL of dialysate Experimental

10 micrograms (µg) of iron/ deciliter (dL) of dialysate

12 µg iron/dL of dialysate Experimental

12 micrograms (µg) of iron/ deciliter (dL) of dialysate

15 µg iron/dL of dialysate Experimental

15 micrograms (µg) of iron/ deciliter (dL) of dialysate

Criteria

Selected Inclusion Criteria:

Adult subject ≥ 18 years of age undergoing chronic hemodialysis for end-stage renal disease (ESRD) three times a week
Hemoglobin (Hgb) values on two successive screening/baseline measures immediately prior to the start of the study averaging 10.1 to 11.5 grams/ deciliter (g/dL), inclusive
Transferrin Saturation (TSAT) values that average 20% or more, but not exceeding 35%, prior to dialysis measured during the screening period
Ferritin values that average 200 to 800 micrograms/ liter (µg/L), inclusive, measured during the screening period. An average ferritin above 800 µg/L but no greater than 1200 µg/L is allowed if the average TSAT is 20% to no greater than 25%.
Except for vascular access surgery, subject has no hospitalization in previous three months for a significant illness that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of the study. No blood transfusions within the last 4 weeks are allowed.
Subject has an adequate dialyzer blood flow rate that is acceptable to the Principal Investigator

Exclusion Criteria:

Hemoglobin (Hgb) values on two successive baseline/screening measurements that average ≥ 11.6g/dL
Subject with a current malignancy involving a site other than skin
Subject with a history of drug or alcohol abuse within the last six months
Subject believed to be unable to complete the entire study (e.g., due to a concurrent disease, life expectancy of less than a year)
Subject who the Principal Investigator considers will be placed at increased risk by the study procedures
Subject requiring hemodialysis more than 3 times per week on a regular basis.
Subject who is unable to discontinue oral iron or intravenous iron supplements for the duration of the study
Subject who is pregnant
Subject considered incompetent to give an informed consent
Subject with a positive test for Hepatitis B Surface Antigen within the past 30 days or during screening
Subject with known HIV infection (if this is not known, no HIV testing will be performed)
Subject with cirrhosis of the liver based on histological criteria or clinical criteria (presence of ascites, esophageal varices, spider nevi, or history of hepatic encephalopathy). Subject with hepatitis C, in the absence of cirrhosis, is not excluded from participation in the study if ALT and AST levels are below 2 times the upper limit of normal consistently during the 2 months preceding enrollment
Subject with active tuberculosis, fungal, viral, or parasitic infection
Subject with active bacterial infection requiring antibiotic therapy
Subject with pre-dialysis Corrected Q-wave to T-wave (QTc) interval ≥ 470 milliseconds (ms)
Subject with a history of hypokalemia, decompensated heart failure, or family history of Long QT Syndrome that in the Investigator's judgment poses a risk for Torsades de Pointe during the study
Subject using concomitant medications known to prolong QT/QTc interval (See Appendix I, TABLE A)
Subject receiving more than 60,000 units or 120 micrograms of erythropoietin (Epogen®, Procrit®, or Aranesp®) per week
Subject has participated in another clinical trial within 30 days of signing Informed Consent

Summary

0 µg Iron/dL of Dialysate

5 µg Iron/dL of Dialysate

10 µg Iron/dL of Dialysate

12 µg Iron/dL of Dialysate

15 µg Iron/dL of Dialysate

All Events

Event Type Organ System Event Term 0 µg Iron/dL of Dialysate 5 µg Iron/dL of Dialysate 10 µg Iron/dL of Dialysate 12 µg Iron/dL of Dialysate 15 µg Iron/dL of Dialysate

Percent of Subjects Whose Hemoglobin (Hgb) Decreases by a Total of 1.0 Grams/ Deciliter (g/dL) (or More) From Baseline on Each of Two Successive Measurements.

Efficacy of a Soluble Ferric Pyrophosphate (SFP)-containing dialysate solution in maintaining physiological iron levels during chronic HD, as measured by the percent of subjects whose hgb decreases by a total of 1.0 g/dL (or more) from baseline on each of two successive measurements. Hemoglobin was obtained weekly at the mid-week dialysis treatments and compared to baseline value (average of two hgb measurements obtained at the two consecutive baseline visits prior to randomization).

0 µg Iron/dL of Dialysate

5.0
Percent of subjects

5 µg Iron/dL of Dialysate

6.0
Percent of subjects

10 µg Iron/dL of Dialysate

5.0
Percent of subjects

12 µg Iron/dL of Dialysate

4.0
Percent of subjects

15 µg Iron/dL of Dialysate

10.0
Percent of subjects

Change From Baseline in Hemoglobin (Hgb)

0 µg Iron/dL of Dialysate

-0.177
grams/ deciliter (g/dL) (Mean)
Standard Deviation: 1.1151

5 µg Iron/dL of Dialysate

0.258
grams/ deciliter (g/dL) (Mean)
Standard Deviation: 1.4643

10 µg Iron/dL of Dialysate

0.462
grams/ deciliter (g/dL) (Mean)
Standard Deviation: 1.2214

12 µg Iron/dL of Dialysate

0.173
grams/ deciliter (g/dL) (Mean)
Standard Deviation: 1.5806

15 µg Iron/dL of Dialysate

-0.018
grams/ deciliter (g/dL) (Mean)
Standard Deviation: 1.2532

Time in Days for Hgb to Decrease by a Total of > = 1.0 g/dL From Baseline on Each of Two Successive Measurements in Each Treatment Group.

Kaplan-Meier Estimate of Time to First Hgb Decrease by >= 1.0 g/dL

0 µg Iron/dL of Dialysate

10th Percentile

94.0
Days

15th Percentile

94.0
Days

20th Percentile

115.0
Days

25th Percentile

115.0
Days

5th Percentile

59.0
Days

5 µg Iron/dL of Dialysate

10th Percentile

31.0
Days

15th Percentile

66.0
Days

20th Percentile

87.0
Days

25th Percentile

108.0
Days

5th Percentile

24.0
Days

10 µg Iron/dL of Dialysate

10th Percentile

106.0
Days

15th Percentile

106.0
Days

20th Percentile

106.0
Days

25th Percentile

115.0
Days

5th Percentile

10.0
Days

12 µg Iron/dL of Dialysate

10th Percentile

45.0
Days

15th Percentile

115.0
Days

20th Percentile

115.0
Days

25th Percentile

150.0
Days

5th Percentile

31.0
Days

15 µg Iron/dL of Dialysate

10th Percentile

31.0
Days

15th Percentile

38.0
Days

20th Percentile

80.0
Days

25th Percentile

94.0
Days

5th Percentile

31.0
Days

Reticulocyte Hemoglobin (CHr) Values Every Four Weeks, and at the End of the Subject's Treatment.

Efficacy of SFP administration in dialysate solution as measured by Chr values every four weeks, and at the end of the Subject's Treatment (up to 26 weeks).

0 µg Iron/dL of Dialysate

Baseline Reticulocyte Hemoglobin

32.55
pg (Mean)
Standard Deviation: 2.084

Reticulocyte Hemoglobin/ End of Trial

30.06
pg (Mean)
Standard Deviation: 1.841

Reticulocyte Hemoglobin/ Final Evaluation

31.85
pg (Mean)
Standard Deviation: 2.796

Reticulocyte Hemoglobin/ Week 1

32.42
pg (Mean)
Standard Deviation: 2.852

Reticulocyte Hemoglobin/ Week 12

31.83
pg (Mean)
Standard Deviation: 2.347

Reticulocyte Hemoglobin/ Week 16

31.45
pg (Mean)
Standard Deviation: 2.546

Reticulocyte Hemoglobin/ Week 20

31.13
pg (Mean)
Standard Deviation: 2.172

Reticulocyte Hemoglobin/ Week 24

30.93
pg (Mean)
Standard Deviation: 2.127

Reticulocyte Hemoglobin/ Week 26

30.78
pg (Mean)
Standard Deviation: 2.638

Reticulocyte Hemoglobin/ Week 4

32.0
pg (Mean)
Standard Deviation: 2.668

Reticulocyte Hemoglobin/ Week 8

32.14
pg (Mean)
Standard Deviation: 2.664

5 µg Iron/dL of Dialysate

Baseline Reticulocyte Hemoglobin

32.98
pg (Mean)
Standard Deviation: 1.763

Reticulocyte Hemoglobin/ End of Trial

31.5
pg (Mean)
Standard Deviation: 2.348

Reticulocyte Hemoglobin/ Final Evaluation

31.68
pg (Mean)
Standard Deviation: 2.386

Reticulocyte Hemoglobin/ Week 1

32.58
pg (Mean)
Standard Deviation: 1.932

Reticulocyte Hemoglobin/ Week 12

32.13
pg (Mean)
Standard Deviation: 1.792

Reticulocyte Hemoglobin/ Week 16

31.95
pg (Mean)
Standard Deviation: 1.866

Reticulocyte Hemoglobin/ Week 20

31.81
pg (Mean)
Standard Deviation: 1.860

Reticulocyte Hemoglobin/ Week 24

31.85
pg (Mean)
Standard Deviation: 1.820

Reticulocyte Hemoglobin/ Week 26

31.32
pg (Mean)
Standard Deviation: 2.404

Reticulocyte Hemoglobin/ Week 4

32.27
pg (Mean)
Standard Deviation: 2.090

Reticulocyte Hemoglobin/ Week 8

32.28
pg (Mean)
Standard Deviation: 2.135

10 µg Iron/dL of Dialysate

Baseline Reticulocyte Hemoglobin

32.86
pg (Mean)
Standard Deviation: 3.192

Reticulocyte Hemoglobin/ End of Trial

31.46
pg (Mean)
Standard Deviation: 2.352

Reticulocyte Hemoglobin/ Final Evaluation

32.19
pg (Mean)
Standard Deviation: 3.026

Reticulocyte Hemoglobin/ Week 1

32.69
pg (Mean)
Standard Deviation: 3.019

Reticulocyte Hemoglobin/ Week 12

32.78
pg (Mean)
Standard Deviation: 1.560

Reticulocyte Hemoglobin/ Week 16

33.05
pg (Mean)
Standard Deviation: 2.396

Reticulocyte Hemoglobin/ Week 20

32.81
pg (Mean)
Standard Deviation: 2.328

Reticulocyte Hemoglobin/ Week 24

32.08
pg (Mean)
Standard Deviation: 2.680

Reticulocyte Hemoglobin/ Week 26

32.2
pg (Mean)
Standard Deviation: 2.372

Reticulocyte Hemoglobin/ Week 4

32.69
pg (Mean)
Standard Deviation: 2.931

Reticulocyte Hemoglobin/ Week 8

32.75
pg (Mean)
Standard Deviation: 2.985

12 µg Iron/dL of Dialysate

Baseline Reticulocyte Hemoglobin

32.34
pg (Mean)
Standard Deviation: 2.975

Reticulocyte Hemoglobin/ End of Trial

30.55
pg (Mean)
Standard Deviation: 2.523

Reticulocyte Hemoglobin/ Final Evaluation

31.65
pg (Mean)
Standard Deviation: 3.409

Reticulocyte Hemoglobin/ Week 1

31.87
pg (Mean)
Standard Deviation: 2.963

Reticulocyte Hemoglobin/ Week 12

31.82
pg (Mean)
Standard Deviation: 3.150

Reticulocyte Hemoglobin/ Week 16

31.86
pg (Mean)
Standard Deviation: 3.410

Reticulocyte Hemoglobin/ Week 20

30.68
pg (Mean)
Standard Deviation: 2.026

Reticulocyte Hemoglobin/ Week 24

30.53
pg (Mean)
Standard Deviation: 2.071

Reticulocyte Hemoglobin/ Week 26

30.72
pg (Mean)
Standard Deviation: 2.515

Reticulocyte Hemoglobin/ Week 4

31.82
pg (Mean)
Standard Deviation: 2.515

Reticulocyte Hemoglobin/ Week 8

31.75
pg (Mean)
Standard Deviation: 2.473

15 µg Iron/dL of Dialysate

Baseline Reticulocyte Hemoglobin

32.64
pg (Mean)
Standard Deviation: 1.858

Reticulocyte Hemoglobin/ End of Trial

30.11
pg (Mean)
Standard Deviation: 2.361

Reticulocyte Hemoglobin/ Final Evaluation

32.13
pg (Mean)
Standard Deviation: 2.246

Reticulocyte Hemoglobin/ Week 1

32.4
pg (Mean)
Standard Deviation: 2.006

Reticulocyte Hemoglobin/ Week 12

32.48
pg (Mean)
Standard Deviation: 1.894

Reticulocyte Hemoglobin/ Week 16

32.25
pg (Mean)
Standard Deviation: 2.382

Reticulocyte Hemoglobin/ Week 20

31.64
pg (Mean)
Standard Deviation: 1.338

Reticulocyte Hemoglobin/ Week 24

31.4
pg (Mean)
Standard Deviation: 1.949

Reticulocyte Hemoglobin/ Week 26

30.43
pg (Mean)
Standard Deviation: 2.600

Reticulocyte Hemoglobin/ Week 4

32.05
pg (Mean)
Standard Deviation: 1.837

Reticulocyte Hemoglobin/ Week 8

32.35
pg (Mean)
Standard Deviation: 1.917

Number of Subjects With Infection Episodes Requiring Antibiotic or Anti-fungal Therapy in Each Treatment Group.

0 µg Iron/dL of Dialysate

2.0
Subjects

5 µg Iron/dL of Dialysate

1.0
Subjects

10 µg Iron/dL of Dialysate

2.0
Subjects

12 µg Iron/dL of Dialysate

15 µg Iron/dL of Dialysate

1.0
Subjects

Number of Subjects With a Rise in Hemoglobin (Hgb) to 12.6 g/dL or More on Two Separate Occasions Measured One Week Apart.

0 µg Iron/dL of Dialysate

6.0
Subjects

5 µg Iron/dL of Dialysate

6.0
Subjects

10 µg Iron/dL of Dialysate

9.0
Subjects

12 µg Iron/dL of Dialysate

7.0
Subjects

15 µg Iron/dL of Dialysate

8.0
Subjects

Total

131
Participants

Age, Continuous

58
years (Mean)
Standard Deviation: 14.07

Age, Categorical

Region of Enrollment

Sex: Female, Male

Overall Study

0 µg Iron/dL of Dialysate

5 µg Iron/dL of Dialysate

10 µg Iron/dL of Dialysate

12 µg Iron/dL of Dialysate

15 µg Iron/dL of Dialysate

Drop/Withdrawal Reasons

0 µg Iron/dL of Dialysate

5 µg Iron/dL of Dialysate

10 µg Iron/dL of Dialysate

12 µg Iron/dL of Dialysate

15 µg Iron/dL of Dialysate