Continuous Soluble Ferric Pyrophosphate (SFP) Iron Delivery Via Dialysate in Hemodialysis Patients (CRUISE 1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rockwell Medical Technologies, Inc.
ClinicalTrials.gov Identifier:
NCT01320202
First received: March 20, 2011
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

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).


Condition Intervention Phase
Renal Failure Chronic Requiring Hemodialysis
Drug: Soluble Ferric Pyrophosphate (SFP)
Device: Standard dialysate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline Hemoglobin at End-of-Treatment: Least-Squares Mean [ Time Frame: Hgb measured weekly; up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline Hemoglobin at End-of-Treatment: Mean Baseline and End-of-Treatment Hgb [ Time Frame: Hgb measured weekly; up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Mean Change in Serum Iron From Pre-dialysis to Post-dialysis. [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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.

  • Mean Change in TSAT (Transferrin) From Pre-dialysis to Post-dialysis. [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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.

  • Mean Change in Unsaturated Iron Binding Capacity (UIBC) From Pre- to Post-dialysis. [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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.

  • Red Blood Cell or Whole Blood Transfusion: Number of Patients Receiving Transfusion [ Time Frame: up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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.

  • Red Blood Cell or Whole Blood Transfusion: Number of Units Transfused [ Time Frame: up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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.

  • Percentage of Change From Baseline to End-of-Treatment (EoT) for: Reticulocyte Hemoglobin Content (CHr), Ferritin, and Pre-Dialysis Serum Iron Panel [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Unsaturated Iron-Binding Capacity (UIBC), Serum Iron, and Total Iron-Binding Capacity (TIBC) [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin Content (CHr) [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin Content (CHr) will be quantified.

  • Change From Baseline to End-of-Treatment (EoT) in Ferritin [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Ferritin will be quantified.

  • Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin will be quantified.

  • Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT) [ Time Frame: Up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT) will be quantified.

  • Variability of Hemoglobin Concentration: Temporal Trend [ Time Frame: Hgb measured weekly; up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    The mean temporal trend of hemoglobin concentration value changes, as measured weekly from baseline until the end of participation in Stage 2.

  • Variability of Hemoglobin Concentration: Residual Standard Deviation [ Time Frame: Hgb measured weekly; up to 48 weeks from the date of randomization ] [ Designated as safety issue: No ]
    The mean residual standard deviation of hemoglobin concentration value changes, as measured weekly from baseline until the end of participation in Stage 2.


Enrollment: 305
Study Start Date: March 2011
Study Completion Date: November 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Soluble Ferric Pyrophosphate (SFP) in dialysate
11 micrograms (µg) of iron / deciliter (dL) of dialysate.
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.
Placebo Comparator: Standard Dialysate
0 micrograms (µg) of iron / deciliter (dL) of dialysate.
Device: Standard dialysate
Patients to receive standard dialysate (no iron) during dialysis 3 or 4 times/week.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01320202

  Show 47 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: NCT01320202     History of Changes
Other Study ID Numbers: RMTI-SFP-4
Study First Received: March 20, 2011
Results First Received: March 20, 2015
Last Updated: April 22, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Rockwell Medical Technologies, Inc.:
End Stage Renal Disease
Hemodialysis
SFP
Hemodialysis-dependent chronic renal failure

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

ClinicalTrials.gov processed this record on May 21, 2015