Clinical trial NCT01322347: Continuous Soluble Ferric Pyrophosphate (SFP) Iron Delivery Via Dialysate in Hemodialysis Patients (CRUISE 2)
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 2) 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: 2011-03-24
Enrollment: 294
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): 1-4weeks 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Stage 2 (Randomized Blinded Treatment): 12 months unless withdrawn prematurely.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 date of randomization
measure: Change From Baseline Hemoglobin at End-of-Treatment: Mean Baseline and End-of-Treatment Hemoglobin
timeFrame: Hgb measured weekly; up to 48 weeks from date of randomization
Secondary outcomes:
measure: Mean Change in Serum Iron From Pre-Dialysis to Post-Dialysis
timeFrame: Up to 48 weeks from date of randomization
measure: Mean Change in Transferrin Saturation From Pre-Dialysis to Post-Dialysis
timeFrame: Up to 48 weeks from date of randomization
measure: Mean Change in Unsaturated Iron-Binding Capacity (UIBC) From Pre-Dialysis to Post-Dialysis
timeFrame: Up to 48 weeks from date of randomization
measure: Red Blood Cell or Whole Blood Transfusion: Number of Patients Who Received a Transfusion
timeFrame: Up to 48 weeks from date of randomization
measure: Red Blood Cell or Whole Blood Transfusion: Number of Units Transfused
timeFrame: Up to 48 weeks from date of randomization
measure: Percentage of Change From Baseline to End-of-Treatment for: Reticulocyte Hemoglobin Content (CHr), Ferritin, and the Pre-Dialysis Serum Iron Panel
timeFrame: up to 48 weeks from date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Unsaturated Iron-Binding Capacity (UIBC), Pre-Dialysis Serum Iron, and Pre-Dialysis Total Iron-Binding Capacity (TIBC)
timeFrame: Up to 48 weeks from date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin (CHr)
timeFrame: Up to 48 weeks from date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Ferritin
timeFrame: Up to 48 weeks from date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin
timeFrame: Up to 48 weeks from date of randomization
measure: Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT)
timeFrame: Up to 48 weeks from date of randomization
measure: Variability of Hemoglobin Concentration: Temporal Trend
timeFrame: up to 48 weeks from date of randomization
measure: Variability of Hemoglobin Concentration: Residual Standard Deviation
timeFrame: up to 48 weeks from date of randomization
Other outcomes:
Locations:
city: Paragould
country: United States
facility: Investigator
state: Arkansas
city: Pine Bluff
country: United States
facility: Investigator
state: Arkansas
city: Alhambra
country: United States
facility: Investigator
state: California
city: Beverly Hills
country: United States
facility: Investigator
state: California
city: Glendale
country: United States
facility: Investigator
state: California
city: La Mesa
country: United States
facility: Investigator
state: California
city: Long Beach
country: United States
facility: Investigator
state: California
city: Lynwood
country: United States
facility: Investigator
state: California
city: Paramount
country: United States
facility: Investigator
state: California
city: Whittier
country: United States
facility: Investigator
state: California
city: Pembroke Pines
country: United States
facility: Investigator
state: Florida
city: Augusta
country: United States
facility: Investigator
state: Georgia
city: Macon
country: United States
facility: Investigator
state: Georgia
city: Meridian
country: United States
facility: Investigator
state: Idaho
city: Hines
country: United States
facility: Investigator
state: Illinois
city: Rockville
country: United States
facility: Investigator
state: Maryland
city: Detroit
country: United States
facility: Investigator
state: Michigan
city: Pontiac
country: United States
facility: Investigator
state: Michigan
city: Southfield
country: United States
facility: Investigator
state: Michigan
city: Eatontown
country: United States
facility: Investigator
state: New Jersey
city: Brooklyn
country: United States
facility: Investigator
state: New York
city: Fresh Meadows
country: United States
facility: Investigator
state: New York
city: Great Neck
country: United States
facility: Investigator
state: New York
city: Orchard Park
country: United States
facility: Investigator
state: New York
city: The Bronx
country: United States
facility: Investigator
state: New York
city: Bethany
country: United States
facility: Investigator
state: Oklahoma
city: Bethlehem
country: United States
facility: Investigator
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigator
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigator
state: Pennsylvania
city: Nashville
country: United States
facility: Investigator
state: Tennessee
city: Nashville
country: United States
facility: Investigator
state: Tennessee
city: Arlington
country: United States
facility: Investigator
state: Texas
city: Fort Worth
country: United States
facility: Investigator
state: Texas
city: Fort Worth
country: United States
facility: Investigator
state: Texas
city: Houston
country: United States
facility: Investigator
state: Texas
city: Houston
country: United States
facility: Investigator
state: Texas
city: San Antonio
country: United States
facility: Investigator
state: Texas
city: Fairfax
country: United States
facility: Investigator
state: Virginia
city: Edmonton
country: Canada
facility: Investogator
state: Alberta
city: Greenfield Park
country: Canada
facility: Investigator
state: Quebec
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.