Clinical trial NCT01320202: Continuous Soluble Ferric Pyrophosphate (SFP) Iron Delivery Via Dialysate in Hemodialysis Patients
Official title: A Randomized, Placebo-Controlled, Phase III Study of Dialysate Containing Soluble Ferric Pyrophosphate (SFP) in Chronic Kidney Disease Patients Receiving Hemodialysis: The Continuous Replacement Using Iron Soluble Equivalents (CRUISE 1) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Renal Failure Chronic Requiring Hemodialysis
Keywords: End Stage Renal Disease
Hemodialysis
SFP
Hemodialysis-dependent chronic renal failure
Lead sponsor: Rockwell Medical Technologies, Inc.
Sponsor class: INDUSTRY
First posted: 2011-03-22
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to confirm the safety and efficacy of Soluble Ferric Pyrophosphate (SFP) dialysate solution in maintaining iron delivery for erythropoiesis in anemic adult patients with chronic kidney disease (CKD) receiving hemodialysis. Efficacy will be measured primarily by the change from baseline in hemoglobin (Hgb).

Detailed description: Screening: 2-3 weeks prior to enrollment in Stage 1.

Stage 1 (Run-In): 1-4 weeks depending on qualification for Stage 2.

Stage 2 (Randomized Blinded Treatment): 12 months unless withdrawn prematurely.

Stage 3 (Open-Label Treatment): The duration of Stage 2 plus Stage 3 is intended to be 18 months regardless of treatment assignment in Stage 2.

Eligibility criteria: Stage 1:

Main Inclusion Criteria:

* Adult subject ≥ 18 years of age undergoing chronic hemodialysis three or four times per week for chronic kidney disease (CKD) for at least 4 months, and expected to remain on hemodialysis three to four times weekly and be able to complete the duration of the study.
* Received IV iron therapy between 6 months and 2 weeks prior to enrollment in order to replace iron losses resulting from hemodialysis procedure.
* Mean Screening Hgb ≥ 9.5 to ≤ 11.5 grams per deciliter (g/dL).
* Mean Screening Transferrin Saturation (TSAT) ≥ 15% to ≤ 40%.
* Mean Screening serum ferritin ≥ 200 to ≤ 800 micrograms per liter (µg/L).
* If being administered epoetin, darbepoetin, or CERA, epoetin dose ≤ 45,000 Units (U)/week, darbepoetin dose ≤ 200 micrograms (µg)/week, or CERA dose ≤ 400 micrograms (µg)/month during the four weeks prior to enrollment.

Main Exclusion Criteria:

* Patient has living kidney donor identified or living-donor kidney transplant scheduled. (Note: Patients awaiting deceased-donor transplant need not be excluded.)
* Vascular access for dialysis with femoral catheter or non-tunneled catheter.
* Received a total of \> 800 milligrams (mg) IV iron during the 8 weeks prior to enrollment
* If being administered an ESA, route of administration change or ESA dose change \> 35% (i.e., \[max - min dose\]/max dose \> 0.35) over the 2 weeks prior to screening.
* Serum albumin \< 3.0 grams per deciliter (g/dL) any time over the 8 weeks prior to enrollment.
* Red Blood Cell (RBC) or whole blood transfusion within 12 weeks prior to enrollment.

Stage 2:

Main Inclusion Criteria:

* Patient currently enrolled in the Stage 1 run-in period of study.
* Undergoing chronic hemodialysis three or four times per week for chronic kidney disease (CKD), and expected to remain on hemodialysis three to four times weekly and be able to complete duration of the study.
* Mean Hgb ≥ 9.5 to ≤ 11.5 g/dL over the three most recent consecutive every-week measurements prior to randomization.
* Stable Hgb defined as ≤ 1.0 g/dL difference between the maximum and minimum Hgb values over the 3 weeks immediately prior to randomization.
* Mean TSAT ≥ 15% to ≤ 40% over the two most recent consecutive every-other-week measurements prior to randomization.
* Mean serum ferritin ≥ 200 to ≤ 800 µg/L over the two most recent consecutive every-other-week measurements prior to randomization.
* If being administered epoetin, darbepoetin, or CERA, epoetin dose ≤ 45,000 U/week, darbepoetin dose ≤ 200 µg/week, or CERA dose ≤ 400 µg/month during the four weeks prior to randomization.

Main Exclusion Criteria:

* Patient has living kidney donor identified or living-donor kidney transplant scheduled. (Note: Patients awaiting deceased-donor transplant need not be excluded.)
* Vascular access for dialysis with femoral catheter or non-tunneled catheter.
* Received any amount of IV iron during the 4 weeks prior to randomization.
* If being administered an (Erythropoietin Stimulating Agent) ESA, change in dose over the 6 weeks immediately prior to randomization.
* Serum albumin \< 3.0 g/dL any time over the 8 weeks prior to randomization.
* RBC or whole blood transfusion during Stage 1.

Stage 3:

Main Inclusion Criteria:

* Patient randomized in Stage 2 who has completed the full duration of Stage 2 and less than 4 weeks have elapsed since completion of Stage 2, OR
* Patient in Stage 2 who has been prematurely withdrawn from Stage 2 for protocol-defined Protocol-Mandated Change in Anemia Management and less than 4 weeks have elapsed since withdrawal from Stage 2, OR
* Patient in Stage 2 who has been prematurely withdrawn from Stage 2 for Hgb \>11.5 g/dL over ≥ 1 week confirmed by ≥ 2 consecutive measurements AND an associated increase in Hgb by ≥ 1 g/dL over 4 weeks.

Main Exclusion Criteria:

* Patient in Stage 2 who has been prematurely withdrawn from Stage 2 for any reason other than as noted in inclusion criteria above.

Primary outcomes:
measure: Change From Baseline Hemoglobin at End-of-Treatment: Least-Squares Mean
timeFrame: Hgb measured weekly; up to 48 weeks from the date of randomization
measure: Change From Baseline Hemoglobin at End-of-Treatment: Mean Baseline and End-of-Treatment Hgb
timeFrame: Hgb measured weekly; up to 48 weeks from the date of randomization
Secondary outcomes:
measure: Mean Change in Serum Iron From Pre-dialysis to Post-dialysis.
timeFrame: Up to 48 weeks from the date of randomization
measure: Mean Change in TSAT (Transferrin) From Pre-dialysis to Post-dialysis.
timeFrame: Up to 48 weeks from the date of randomization
measure: Mean Change in Unsaturated Iron Binding Capacity (UIBC) From Pre- to Post-dialysis.
timeFrame: Up to 48 weeks from the date of randomization
measure: Red Blood Cell or Whole Blood Transfusion: Number of Patients Receiving Transfusion
timeFrame: up to 48 weeks from the date of randomization
measure: Red Blood Cell or Whole Blood Transfusion: Number of Units Transfused
timeFrame: up to 48 weeks from the date of randomization
measure: Percentage of Change From Baseline to End-of-Treatment (EoT) for: Reticulocyte Hemoglobin Content (CHr), Ferritin, and Pre-Dialysis Serum Iron Panel
timeFrame: Up to 48 weeks from the date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Unsaturated Iron-Binding Capacity (UIBC), Serum Iron, and Total Iron-Binding Capacity (TIBC)
timeFrame: Up to 48 weeks from the date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin Content (CHr)
timeFrame: Up to 48 weeks from the date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Ferritin
timeFrame: Up to 48 weeks from the date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin
timeFrame: Up to 48 weeks from the date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT)
timeFrame: Up to 48 weeks from the date of randomization
measure: Variability of Hemoglobin Concentration: Temporal Trend
timeFrame: Hgb measured weekly; up to 48 weeks from the date of randomization
measure: Variability of Hemoglobin Concentration: Residual Standard Deviation
timeFrame: Hgb measured weekly; up to 48 weeks from the date of randomization
Other outcomes:
Locations:
city: Bakersfield
country: United States
state: California
city: Chula Vista
country: United States
facility: Investigative Site
state: California
city: Cudahy
country: United States
state: California
city: Downey
country: United States
state: California
city: Encino
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: National City
country: United States
state: California
city: Northridge
country: United States
state: California
city: Ontario
country: United States
state: California
city: Panorama City
country: United States
state: California
city: Riverside
country: United States
state: California
city: San Dimas
country: United States
state: California
city: Simi Valley
country: United States
state: California
city: West Covina
country: United States
state: California
city: Yuba City
country: United States
state: California
city: Waterbury
country: United States
facility: Investigative Site
state: Connecticut
city: Waterbury
country: United States
state: Connecticut
city: Coral Springs
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Augusta
country: United States
facility: Investigative Site
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Michigan City
country: United States
state: Indiana
city: Detroit
country: United States
state: Michigan
city: Las Vegas
country: United States
state: Nevada
city: Mineola
country: United States
facility: Investigative Site
state: New York
city: Ridgewood
country: United States
facility: Investigative Site
state: New York
city: Rosedale
country: United States
state: New York
city: Yonkers
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Sumter
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
facility: Investigative Site
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Shorewood
country: United States
state: Wisconsin
city: Caguas
country: Puerto Rico
city: Carolina
country: Puerto Rico
Study officials:
affiliation: Rockwell Medical
name: Ray Pratt, MD
role: STUDY_DIRECTOR
References:
citation: Fishbane SN, Singh AK, Cournoyer SH, Jindal KK, Fanti P, Guss CD, Lin VH, Pratt RD, Gupta A. Ferric pyrophosphate citrate (Triferic) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients. Nephrol Dial Transplant. 2015 Dec;30(12):2019-26. doi: 10.1093/ndt/gfv277. Epub 2015 Jul 13.