Continuous Soluble Ferric Pyrophosphate (SFP) Iron Delivery Via Dialysate in Hemodialysis Patients

NCT01286012 | Completed Phase 2 Results

• 1 other identifier: NIH-FP-01 PRIME
• Study Type: interventional
• Target: 108
• Locations: 2 countries
• Sites: 23

Brief Summary

The purpose of this study is to compare the clinical safety and efficacy of SFP in sparing the need for erythropoiesis stimulating agents (ESAs) required to maintain hemoglobin (hgb) levels in chronic hemodialysis subjects who receive SFP via the dialysate versus subjects who receive conventional dialysate without iron.

Conditions

End Stage Renal Disease

Keywords

End Stage Renal Disease, Hemodialysis, SFP

Outcome Measures

Primary Outcomes (1)

• The Percent Change From Baseline in ESA Dose Required to Maintain Hemoglobin in the Target Range, Adjusted for Hgb.

  The statistical endpoint is the change from baseline between groups at End of Treatment, where the baseline prescribed ESA dose (expressed as U/week epoetin) per subject is defined as the average weekly dose of ESA prescribed for administration over the two-week period of time immediately prior to randomization. The end-of-treatment prescribed ESA dose (expressed as U/week epoetin) per subject is defined as the average weekly dose of ESA prescribed for administration over the last two weeks of the treatment period.

  Hemoglobin measured weekly and serum ferritin and Transferrin Saturation (TSAT) determined every other week; ESA dose recorded at each visit for 36 weeks.

Secondary Outcomes (4)

• The Distribution of Changes From Baseline in the Prescribed ESA Dose Between the Two Treatment Arms

  ESA dose is monitored and recorded at each dialysis session for 36 weeks.

• Stability of Hemoglobin Over Time (Maintenance of Hemoglobin Between 9.5-11.5 g/dL.

  36 weeks

• The Amount of Supplemental Intravenous (IV) Iron Needed During Study Participation.

  36 weeks

• Comparison of Iron Delivery to the Erythron From Baseline to End of Treatment Between the Treatment Groups.

  36 weeks

Study Arms (2)

SFP in liquid bicarbonate

ACTIVE COMPARATOR

Drug: Soluble Ferric Pyrophosphate in liquid bicarbonate; Drug: Erythrocyte Stimulating Agent (ESA); Drug: Intravenous (IV) Iron

Placebo: Conventional Liquid Bicarbonate

PLACEBO COMPARATOR

Control concentrate lacking SFP does not contain SFP (total iron = 0)

Drug: Placebo: Conventional liquid bicarbonate; Drug: Erythrocyte Stimulating Agent (ESA); Drug: Intravenous (IV) Iron

Interventions

Soluble Ferric Pyrophosphate in liquid bicarbonate DRUG

Subjects will receive hemodialysis containing SFP at 2 µM (11 µg iron/dL of dialysate) at every dialysis session, for a total duration of 36 weeks.

Also known as: SFP

SFP in liquid bicarbonate

Placebo: Conventional liquid bicarbonate DRUG

Subjects will receive hemodialysis containing conventional liquid bicarbonate lacking SFP at every dialysis session, for a total duration of 36 weeks.

Placebo: Conventional Liquid Bicarbonate

Erythrocyte Stimulating Agent (ESA) DRUG

ESA was administered according to the recommendation of a blinded central anemia management center (CAMC) based on the weekly hemoglobin value and its rate of change.

Placebo: Conventional Liquid Bicarbonate; SFP in liquid bicarbonate

Intravenous (IV) Iron DRUG

Approved IV iron preparations were administered per a protocol driven algorithm when patients serum ferritin value decreased below 200 ug/L.

Placebo: Conventional Liquid Bicarbonate; SFP in liquid bicarbonate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects ≥ 18 years of age.
• End-stage renal disease undergoing maintenance hemodialysis 3 to 4 times a week for at least 4 months and expected to remain on this schedule and be able to complete the study. Subjects on a cadaveric transplant list need not be excluded for this reason unless there is an identified donor.
• Mean Hgb in the range of ≥ 9.5 to ≤ 12.0 g/dL during screening.
• The difference between the maximum and minimum Hgb values during screening does not exceed 1.0 g/dL.
• Mean ferritin ≥ 200 to ≤ 1000 µg/L during screening.
• Mean TSAT ≥ 15% to ≤ 40% during screening.
• Any and all serum albumin measured during the 2 months preceding randomization must be ≥ 3.0 g/dL.
• Prescribed ESA dosing remaining in the range of ≥ 4,000 to ≤ 45,000 U/week epoetin or ≥ 12.5 to ≤ 200 µg/week darbepoetin during the 6 weeks preceding randomization.
• Required IV iron at any time in the 6 months preceding randomization.

You may not qualify if:

• Vascular access for dialysis is a catheter.
• During the 6 months prior to randomization, infection of the vascular access to be used at the time of randomization.
• Received a total of \> 600 mg IV iron during the 6 weeks prior to randomization.
• Received any amount of IV or oral iron during the 2 weeks prior to randomization.
• Change in prescribed ESA dose:
• Any change in prescribed ESA dose within 4 weeks prior to randomization.
• The prescribed ESA dose at the time of randomization is \> 25% higher or lower than the prescribed dose at 6 weeks prior to randomization.
• Change in prescribed type of ESA (e.g., epoetin vs. darbepoetin) or route of administration within 6 weeks prior to randomization.
• Actual ESA dosing missed or withheld for a cumulative total of ≥ 1 week for any reason during the 6 weeks prior to randomization.
• Known cause of anemia other than anemia attributable to renal disease (e.g., sickle cell disease, thalassemia, pure red cell aplasia, hemolytic anemia, myelodysplastic syndrome, etc.)
• Scheduled kidney transplant or a donor has been identified but the transplant has not been scheduled.
• Known ongoing inflammatory disorder (other than Chronic Kidney Disease), such as systemic lupus erythematosus, rheumatoid arthritis, other collagen-vascular diseases, etc.
• \. Known active 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. Subjects with hepatitis C, in the absence of cirrhosis, are not excluded from participation in the study if Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are below 2 times the upper limit of normal on a consistent basis during the 2 months preceding randomization.
• \. Occult tuberculosis requiring prophylactic treatment with anti-tubercular drug(s) that overlaps with the patient's participation in this study.
• \. Cirrhosis of the liver based on histological criteria or clinical criteria (e.g., presence of ascites, esophageal varices, spider nevi, or history of hepatic encephalopathy).

Sponsors & Collaborators

• Rockwell Medical Technologies, Inc.: lead

Study Sites (23)

Investigator

Birmingham, Alabama, 35211, United States

Location

Investigator

Tempe, Arizona, 85284, United States

Location

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Granada Hills, California, 91344, United States

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Colorado Springs, Colorado, 80909, United States

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Miami, Florida, 33128, United States

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Miami, Florida, 33173, United States

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Albany, Georgia, 31702, United States

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Hayden, Idaho, 83835, United States

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Louisville, Kentucky, 40202, United States

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New Orleans, Louisiana, 70122, United States

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Columbus, Mississippi, 39705, United States

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Kansas City, Missouri, 64114, United States

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Las Vegas, Nevada, 89120, United States

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Paterson, New Jersey, 07503, United States

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Lexington, North Carolina, 27292, United States

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Columbia, Tennessee, 38401, United States

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Duncanville, Texas, 75137, United States

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Greenville, Texas, 75402, United States

Location

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San Antonio, Texas, 78215, United States

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San Antonio, Texas, 78221, United States

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St. George, Utah, 84770, United States

Location

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Taylorsville, Utah, 84118, United States

Location

Investigator

Fajardo, 00738, Puerto Rico

Location

Related Publications (1)

• Gupta A, Lin V, Guss C, Pratt R, Ikizler TA, Besarab A. Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients. Kidney Int. 2015 Nov;88(5):1187-94. doi: 10.1038/ki.2015.203. Epub 2015 Jul 8.

  PMID: 26154926 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

spleen fibrinolytic proteinase (human); Iron

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Results Point of Contact

• Title: Raymond Pratt, MD CMO
• Organization: Rockwell Medical

rd@rockwellmed.com

248 960 9009

Study Officials

• Ray Pratt, MD

  Rockwell Medical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2011
• First Posted: January 31, 2011
• Study Start: January 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: October 1, 2018
• Results First Posted: March 26, 2014

Record last verified: 2018-08

Locations

PR (1); US (22)