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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rockwell Medical Technologies, Inc.
ClinicalTrials.gov Identifier:
NCT01286012
First received: January 18, 2011
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
End Stage Renal Disease
Drug: Soluble Ferric Pyrophosphate in liquid bicarbonate
Drug: Placebo: Conventional liquid bicarbonate
Drug: Erythrocyte Stimulating Agent (ESA)
Drug: Intravenous (IV) Iron
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Physiological Iron Maintenance in End Stage Renal Disease (ESRD) Subjects by Delivery of Soluble Ferric Pyrophosphate (SFP) Via Hemodialysate: The PRIME Study

Resource links provided by NLM:


Further study details as provided by Rockwell Medical Technologies, Inc.:

Primary Outcome Measures:
  • The Percent Change From Baseline in ESA Dose Required to Maintain Hemoglobin in the Target Range, Adjusted for Hgb. [ Time Frame: Hemoglobin measured weekly and serum ferritin and Transferrin Saturation (TSAT) determined every other week; ESA dose recorded at each visit for 36 weeks. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • The Incidence of "Patient Responders" Defined as ≥ 25% Decrease From Baseline in ESA Dose Sustained Continuously for ≥ 8 Weeks. [ Time Frame: ESA dose is monitored and recorded at each dialysis session for 36 weeks. ] [ Designated as safety issue: No ]
  • The Incidence of "Patient Failures," Defined as ≥ 25% Increase From Baseline in ESA Dose Sustained Continuously for ≥ 8 Weeks. [ Time Frame: ESA dose is monitored and recorded at each dialysis session for 36 weeks. ] [ Designated as safety issue: No ]
  • Stability of Hemoglobin Over Time (Maintenance of Hemoglobin Between 9.5-11.5 g/dL, and Variability in Hemoglobin [Hgb-var]). [ Time Frame: measured weekly for 36 weeks. ] [ Designated as safety issue: No ]
  • The Amount of Supplemental Intravenous (IV) Iron Needed. [ Time Frame: Recorded at every dialysis session for 36 weeks ] [ Designated as safety issue: No ]
  • Markers of Inflammation and Oxidative Stress [ Time Frame: measured pre and post-dialysis at Week 1 Visit 2 and pre-dialysis at Weeks 4, 12, 24, and 36 of the study. ] [ Designated as safety issue: Yes ]
  • Iron Delivery to the Erythron as Estimated by Hemoglobin Generation in Response to Erythropoietin (ESA Response Index, or ERI, Calculated as ESA Dose/Hgb). The ERI Will Also be Divided by Body Weight in Kilograms to Obtain a Modified ERI (ERI/kg). [ Time Frame: Hemoglobin measured weekly; ESA dose recorded at each visit for 36 weeks, pre-dialysis body weight recorded at each visit for the first four weeks of the study and then weekly for the rest of the study. ] [ Designated as safety issue: No ]

Enrollment: 108
Study Start Date: January 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: SFP in liquid bicarbonate Drug: Soluble Ferric Pyrophosphate in liquid bicarbonate
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.
Other Name: SFP
Drug: Erythrocyte Stimulating Agent (ESA)
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.
Drug: Intravenous (IV) Iron
Approved IV iron preparations were administered per a protocol driven algorithm when patients serum ferritin value decreased below 200 ug/L.
Placebo Comparator: Placebo: Conventional Liquid Bicarbonate
Control concentrate lacking SFP does not contain SFP (total iron = 0)
Drug: Placebo: Conventional liquid bicarbonate
Subjects will receive hemodialysis containing conventional liquid bicarbonate lacking SFP at every dialysis session, for a total duration of 36 weeks.
Drug: Erythrocyte Stimulating Agent (ESA)
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.
Drug: Intravenous (IV) Iron
Approved IV iron preparations were administered per a protocol driven algorithm when patients serum ferritin value decreased below 200 ug/L.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  1. Male and female subjects ≥ 18 years of age.
  2. 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.
  3. Mean Hgb in the range of ≥ 9.5 to ≤ 12.0 g/dL during screening.
  4. The difference between the maximum and minimum Hgb values during screening does not exceed 1.0 g/dL.
  5. Mean ferritin ≥ 200 to ≤ 1000 µg/L during screening.
  6. Mean TSAT ≥ 15% to ≤ 40% during screening.
  7. Any and all serum albumin measured during the 2 months preceding randomization must be ≥ 3.0 g/dL.
  8. 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.
  9. Required IV iron at any time in the 6 months preceding randomization.

Main Exclusion Criteria:

  1. Vascular access for dialysis is a catheter.
  2. During the 6 months prior to randomization, infection of the vascular access to be used at the time of randomization.
  3. Received a total of > 600 mg IV iron during the 6 weeks prior to randomization.
  4. Received any amount of IV or oral iron during the 2 weeks prior to randomization.
  5. Change in prescribed ESA dose:

    1. Any change in prescribed ESA dose within 4 weeks prior to randomization.
    2. The prescribed ESA dose at the time of randomization is > 25% higher or lower than the prescribed dose at 6 weeks prior to randomization.
    3. Change in prescribed type of ESA (e.g., epoetin vs. darbepoetin) or route of administration within 6 weeks prior to randomization.
  6. Actual ESA dosing missed or withheld for a cumulative total of ≥ 1 week for any reason during the 6 weeks prior to randomization.
  7. 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.)
  8. Scheduled kidney transplant or a donor has been identified but the transplant has not been scheduled.
  9. Known ongoing inflammatory disorder (other than Chronic Kidney Disease), such as systemic lupus erythematosus, rheumatoid arthritis, other collagen-vascular diseases, etc.

11. 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.

12. Occult tuberculosis requiring prophylactic treatment with anti-tubercular drug(s) that overlaps with the patient's participation in this study.

13. 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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286012

  Show 23 Study Locations
Sponsors and Collaborators
Rockwell Medical Technologies, Inc.
Investigators
Study Director: Ajay Gupta, MD Rockwell Medical
  More Information

No publications provided

Responsible Party: Rockwell Medical Technologies, Inc.
ClinicalTrials.gov Identifier: NCT01286012     History of Changes
Other Study ID Numbers: NIH-FP-01 PRIME
Study First Received: January 18, 2011
Results First Received: February 3, 2014
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Rockwell Medical Technologies, Inc.:
End Stage Renal Disease, Hemodialysis, SFP

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Iron
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014