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

Renal Failure Chronic Requiring Hemodialysis Clinical Trial

— CRUISE 1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01320202
• Other study ID #: RMTI-SFP-4
• Status: Completed
• Phase: Phase 3
• First received: March 20, 2011
• Last updated: April 24, 2017
• Start date: March 2011
• Est. completion date: November 2013

Study information

• Verified date: April 2017
• Source: Rockwell Medical Technologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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Stage 2 (Randomized Blinded Treatment): 12 months unless withdrawn prematurely.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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: November 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Failure Chronic Requiring Hemodialysis
• Renal Insufficiency

Intervention

Drug:
• Soluble Ferric Pyrophosphate (SFP)
Patients to receive 11 micrograms (µg) of iron/ deciliter (dL) of dialysate during dialysis 3 or 4 times/week for up to 18 months.

Device:
• Standard dialysate
Patients to receive standard dialysate (no iron) during dialysis 3 or 4 times/week.

Locations

Country	Name	City	State
United States	Investigative Site	Augusta	Georgia
United States	Investigative Site	Chula Vista	California
United States	Investigative Site	Houston	Texas
United States	Investigative Site	Mineola	New York
United States	Investigative Site	Ridgewood	New York
United States	Investigative Site	Waterbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Rockwell Medical Technologies, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline Hemoglobin at End-of-Treatment: Least-Squares Mean	Mean change from baseline Hgb (the average of the three most recent Hgb values preceding randomization) assessments during the last one-sixth of the treatment period for patients who prematurely withdraw from study treatment, but will include a minimum of at least the last two Hgb values. Value is expressed as least-squares mean with standard error.	Hgb measured weekly; up to 48 weeks from the date of randomization
Primary	Change From Baseline Hemoglobin at End-of-Treatment: Mean Baseline and End-of-Treatment Hgb	Mean change from baseline Hgb (the average of the three most recent Hgb values preceding randomization) assessments during the last one-sixth of the treatment period for patients who prematurely withdraw from study treatment, but will include a minimum of at least the last two Hgb values. Values expressed are mean baseline and end-of-treatment Hgb, along with the mean difference (standard deviation).	Hgb measured weekly; up to 48 weeks from the date of randomization
Secondary	Mean Change in Serum Iron From Pre-dialysis to Post-dialysis.	The mean difference between the pre-dialysis and post-dialysis serum iron was calculated, using all post-baseline values obtained during Stage 2. Subjects could participate in Stage 2 for up to 48 weeks, provided that they did not complete Stage 2 early due to a protocol-mandated change in anemia management or withdraw from the study entirely for other reasons.	Up to 48 weeks from the date of randomization
Secondary	Mean Change in TSAT (Transferrin) From Pre-dialysis to Post-dialysis.	The mean difference between the pre-dialysis and post-dialysis TSAT (transferrin) was calculated, using all post-baseline values obtained during Stage 2. Subjects could participate in Stage 2 for up to 48 weeks, provided that they did not complete Stage 2 early due to a protocol-mandated change in anemia management or withdraw from the study entirely for other reasons.	Up to 48 weeks from the date of randomization
Secondary	Mean Change in Unsaturated Iron Binding Capacity (UIBC) From Pre- to Post-dialysis.	The mean difference between the pre-dialysis and post-dialysis unsaturated iron binding capacity (UIBC) was calculated, using all post-baseline values obtained during Stage 2. Subjects could participate in Stage 2 for up to 48 weeks, provided that they did not complete Stage 2 early due to a protocol-mandated change in anemia management or withdraw from the study entirely for other reasons.	Up to 48 weeks from the date of randomization
Secondary	Red Blood Cell or Whole Blood Transfusion: Number of Patients Receiving Transfusion	The number of patients requiring red blood cell or whole blood transfusion while in the randomized treatment stage (Stage 2). Patients remained in Stage 2 until they met protocol-defined criteria for Stage 2 completion or until they had participated in Stage 2 for 48 weeks (whichever came sooner). If a patient was transfused, they were withdrawn from Stage 2.	up to 48 weeks from the date of randomization
Secondary	Red Blood Cell or Whole Blood Transfusion: Number of Units Transfused	The total number of units of red blood cells or whole blood that were received by patients while in the randomized treatment stage (Stage 2). This number is the total number of units received across all randomized patients in each treatment group (it is not the average number of units received per patient). Patients remained in Stage 2 until they met protocol-defined criteria for Stage 2 completion or until they had participated in Stage 2 for 48 weeks (whichever came sooner). If a patient was transfused, they were withdrawn from Stage 2.	up to 48 weeks from the date of randomization
Secondary	Percentage of Change From Baseline to End-of-Treatment (EoT) for: Reticulocyte Hemoglobin Content (CHr), Ferritin, and Pre-Dialysis Serum Iron Panel	A comparison of the lab values at the end-of-treatment (EoT) to baseline was performed, and the percentage of change from baseline was calculated for the following lab parameters: reticulocyte hemoglobin content (CHr), Ferritin, pre-dialysis unbound iron-binding capacity (UIBC), pre-dialysis serum iron, pre-dialysis transferrin, pre-dialysis total iron-binding capacity TIBC), and transferrin saturation (TSAT).	Up to 48 weeks from the date of randomization
Secondary	Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Unsaturated Iron-Binding Capacity (UIBC), Serum Iron, and Total Iron-Binding Capacity (TIBC)	The Mean Change from Stage 2 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) will be quantified.	Up to 48 weeks from the date of randomization
Secondary	Change From Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin Content (CHr)	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin Content (CHr) will be quantified.	Up to 48 weeks from the date of randomization
Secondary	Change From Baseline to End-of-Treatment (EoT) in Ferritin	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Ferritin will be quantified.	Up to 48 weeks from the date of randomization
Secondary	Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin will be quantified.	Up to 48 weeks from the date of randomization
Secondary	Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT)	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT) will be quantified.	Up to 48 weeks from the date of randomization
Secondary	Variability of Hemoglobin Concentration: Temporal Trend	The mean temporal trend of hemoglobin concentration value changes, as measured weekly from baseline until the end of participation in Stage 2.	Hgb measured weekly; up to 48 weeks from the date of randomization
Secondary	Variability of Hemoglobin Concentration: Residual Standard Deviation	The mean residual standard deviation of hemoglobin concentration value changes, as measured weekly from baseline until the end of participation in Stage 2.	Hgb measured weekly; up to 48 weeks from the date of randomization