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

• ClinicalTrials.gov Identifier: NCT01286012
• Recruitment Status: Completed
• First Posted: January 31, 2011
• Results First Posted: March 26, 2014
• Last Update Posted: October 1, 2018
• Sponsor: Rockwell Medical Technologies, Inc.
• Information provided by (Responsible Party): Rockwell Medical Technologies, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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
• Study Start Date: January 2011
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: January 2013

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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. ]
   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 :

1. The Distribution of Changes From Baseline in the Prescribed ESA Dose Between the Two Treatment Arms [ Time Frame: ESA dose is monitored and recorded at each dialysis session for 36 weeks. ]
   The change from baseline in prescribed ESA dose at end-of-treatment was categorized as being greater than or equal to 25%, 10 to less than 25%, -10 to 10%, greater than -25 to -10% and less than or equal to -25%. The number of subjects in each treatment group that fit each category was compared.
2. Stability of Hemoglobin Over Time (Maintenance of Hemoglobin Between 9.5-11.5 g/dL. [ Time Frame: 36 weeks ]
   The number of patients in each treatment group who had maintained their hemoglobin between 95 and 115 grams/liter at the end of treatment was quantified.
3. The Amount of Supplemental Intravenous (IV) Iron Needed During Study Participation. [ Time Frame: 36 weeks ]
   The absolute amount of IV iron administered to subjects in each treatment group was divided by the number of weeks on study and the number of subjects per treatment group such that the mean dose of IV iron (mg) per week per subject (for the entire treatment group) was calculated.
4. Comparison of Iron Delivery to the Erythron From Baseline to End of Treatment Between the Treatment Groups. [ Time Frame: 36 weeks ]
   Iron delivery to the erythron was estimated by Hgb generation in response to erythropoietin (ERI, calculated as ESA dose/Hgb). In addition, ERI was also divided by body weight in kilograms to obtain a modified ERI (ERI/kg).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Alabama

Investigator

Birmingham, Alabama, United States, 35211

United States, Arizona

Investigator

Tempe, Arizona, United States, 85284

United States, California

Investigator

Granada Hills, California, United States, 91344

United States, Colorado

Investigator

Colorado Springs, Colorado, United States, 80909

United States, Florida

Investigator

Miami, Florida, United States, 33128

Investigator

Miami, Florida, United States, 33173

United States, Georgia

Investigator

Albany, Georgia, United States, 31702

United States, Idaho

Investigator

Hayden, Idaho, United States, 83835

United States, Kentucky

Investigator

Louisville, Kentucky, United States, 40202

United States, Louisiana

Investigator

New Orleans, Louisiana, United States, 70122

United States, Mississippi

Investigator

Columbus, Mississippi, United States, 39705

United States, Missouri

Investigator

Kansas City, Missouri, United States, 64114

United States, Nevada

Investigator

Las Vegas, Nevada, United States, 89120

United States, New Jersey

Investigator

Paterson, New Jersey, United States, 07503

United States, North Carolina

Investigator

Lexington, North Carolina, United States, 27292

United States, Tennessee

Investigator

Columbia, Tennessee, United States, 38401

United States, Texas

Investigator

Duncanville, Texas, United States, 75137

Investigator

Greenville, Texas, United States, 75402

Investigator

San Antonio, Texas, United States, 78215

Investigator

San Antonio, Texas, United States, 78221

United States, Utah

Investigator

Saint George, Utah, United States, 84770

Investigator

Taylorsville, Utah, United States, 84118

Puerto Rico

Investigator

Fajardo, Puerto Rico, 00738

Sponsors and Collaborators

Rockwell Medical Technologies, Inc.

Investigators

• Study Director: Ray Pratt, MD; Rockwell Medical

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Rockwell Medical Technologies, Inc.
• ClinicalTrials.gov Identifier: NCT01286012
• Other Study ID Numbers: NIH-FP-01 PRIME
• First Posted: January 31, 2011
• Results First Posted: March 26, 2014
• Last Update Posted: October 1, 2018
• Last Verified: August 2018

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