Hyperphosphatemia
Conditions
Brief summary
Transition to Ferric Citrate among Hemodialysis and Peritoneal Dialysis Patients: A Phase 4 Real World Experience Study from Kaiser Permanente Southern California
Detailed description
PROTOCOL SUMMARY Title: Transition to Ferric Citrate among Hemodialysis and Peritoneal Dialysis Patients: A Phase 4 Real World Experience Study from Kaiser Permanente Southern California Short Title: FeCitrate Protocol Number: KP FeCitrate Study Phase: 4 Study Site(s): Los Angeles Kaiser Sunset Medical Center Number of Subjects: 55 Study Arms: 1 Indication: Hyperphosphatemia in end stage renal disease Primary Purpose: To evaluate the efficacy of ferric citrate for control of serum phosphorus levels and maintenance of adequate iron stores among dialysis-dependent patients before and after conversion from traditional phosphate binders in a real world environment Overview of Study Design: Prospective non-randomized cohort study of 6-9 months duration (active study period 6 months). Investigational Product Administration: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption. Study Endpoint: Mean serum phosphorus levels and rate of successful phosphorus control (\<5.5mg/dl) 6 months before and after treatment with ferric citrate Statistical Methods: Not powered to detect statistical significance
Interventions
DRUGFerric Citrate
One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption.
Sponsors
Keryx Biopharmaceuticals
Kaiser Permanente
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Prospective non-randomized cohort study of 6-9 months duration (active study period 6 months).
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Currently using 3 to 18 pills per day of calcium acetate, sevelamer, lanthanum, or calcium carbonate * Mean serum phosphorus 4.0-\<8.0 mg/dl for 6 months prior to enrollment * No allergy to iron * Mean corrected serum calcium \> 8.0 mg/dl for 6 months prior to enrollment * Mean PTH \< 1000 pg/ml for 6 months prior to enrollment * Mean ferritin \< 1500 ng/ml and mean iron sat \< 50% for 6 months prior to enrollment
Exclusion criteria
* History of gastrointestinal bleeding within past 6 months * History of hospitalization for gastroparesis, bowel obstruction, or abdominal surgery within past 6 months * Acute kidney injury equal to or less than 3 months before the initial screening date * Active malignancy * Functioning renal transplant * Patients with iron overload syndrome (e.g., Hemochromatosis) * History autoimmune disease, hemoglobinopathy, hemochromatosis, sickle cell disease * Active or past history of calciphylaxis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phosphorus Levels | 6 months | Serum phosphorus levels measured by mg/dL from the 6 months prior to enrollment were compared to serum phosphorus levels collected during the 6 months of ferric citrate use |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intravenous (IV) Iron | 6 months | The amount of intravenous (IV) iron in mg used per month by participants for 6 months before and 6 months on Ferric Citrate treatment. |
| Erythropoiesis Stimulating Agents (ESA) Dose | 6 months | Mean Erythropoiesis Stimulating Agents (ESA) use from the 6 months prior to enrollment were compared to ESA use during the 6 months of ferric citrate use. The mean ESA dose units given to each participant per month was used in the analysis of this outcome. |
| Median Pill Count | 6 months | median pill count of ferric citrate pills/day required to maintain phosphorus control |
Countries
United States
Participant flow
Recruitment details
Study subjects who received either hemodialysis (HD) or peritoneal dialysis (PD) at Kaiser Permanente Southern California, Los Angeles Medical Center were eligible for recruitment.
Pre-assignment details
No pre-assignment events. 55 subjects were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Ferric Citrate - Hemodialysis Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles.
Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption. | 21 |
| Ferric Citrate - Peritoneal Dialysis Auryxia, 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles.
Ferric Citrate: One to two tablets of Ferric Citrate phosphorus binder administered by mouth before every meal to prevent dietary phosphorus absorption. | 26 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 8 |
| Overall Study | Protocol withdrawal criteria-off drug > 2 weeks | 3 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Ferric Citrate - Hemodialysis | Total | Ferric Citrate - Peritoneal Dialysis |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 13 | 60 years STANDARD_DEVIATION 14 | 57 years STANDARD_DEVIATION 14 |
| Body Mass Index (BMI) | 28.4 kg/m^2 STANDARD_DEVIATION 4.7 | 28.1 kg/m^2 STANDARD_DEVIATION 4.9 | 27.8 kg/m^2 STANDARD_DEVIATION 5.2 |
| Cerebrovascular Disease | 6 Participants | 8 Participants | 2 Participants |
| Congestive Heart Failure | 5 Participants | 9 Participants | 4 Participants |
| Diabetes | 8 Participants | 15 Participants | 7 Participants |
| Duration on Dialysis | 29 months STANDARD_DEVIATION 32.1 | 36.2 months STANDARD_DEVIATION 42.5 | 41.4 months STANDARD_DEVIATION 49.2 |
| Ischemic Heart Failure | 2 Participants | 4 Participants | 2 Participants |
| Peripheral Vascular Disease | 5 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized African American | 6 Participants | 9 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 13 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic | 7 Participants | 19 Participants | 12 Participants |
| Race/Ethnicity, Customized Not Hispanic | 14 Participants | 27 Participants | 13 Participants |
| Race/Ethnicity, Customized Unknown Ethnicity | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown Race | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 21 Participants | 14 Participants |
| Region of Enrollment United States | 21 participants | 47 participants | 26 participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 15 Participants | 34 Participants | 19 Participants |
| Smoking | 10 Participants | 16 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 23 / 27 | 27 / 27 |
| serious Total, serious adverse events | 7 / 27 | 10 / 27 |
Outcome results
Primary
Phosphorus Levels
Serum phosphorus levels measured by mg/dL from the 6 months prior to enrollment were compared to serum phosphorus levels collected during the 6 months of ferric citrate use
Time frame: 6 months
Population: The final analysis included 21 Hemodialysis and 26 Peritoneal Dialysis patients after exclusion of early dropouts. Wilcoxon signed rank test was used to compare pre-treatment and on-treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Citrate - Hemodialysis | Phosphorus Levels | Pre-treatment | 5.3 mg/dL | Standard Deviation 1 |
| Ferric Citrate - Hemodialysis | Phosphorus Levels | On-treatment | 5.4 mg/dL | Standard Deviation 1.1 |
| Ferric Citrate - Peritoneal Dialysis | Phosphorus Levels | Pre-treatment | 5.6 mg/dL | Standard Deviation 0.8 |
| Ferric Citrate - Peritoneal Dialysis | Phosphorus Levels | On-treatment | 6 mg/dL | Standard Deviation 1.8 |
Secondary
Erythropoiesis Stimulating Agents (ESA) Dose
Mean Erythropoiesis Stimulating Agents (ESA) use from the 6 months prior to enrollment were compared to ESA use during the 6 months of ferric citrate use. The mean ESA dose units given to each participant per month was used in the analysis of this outcome.
Time frame: 6 months
Population: The final analysis included 21 Hemodialysis and 26 Peritoneal Dialysis patients after exclusion of early dropouts. Wilcoxon signed rank test was used to compare pre-treatment and post-treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Citrate - Hemodialysis | Erythropoiesis Stimulating Agents (ESA) Dose | Pre-Treatment | 28761.1 units/mo | Standard Deviation 41314.1 |
| Ferric Citrate - Hemodialysis | Erythropoiesis Stimulating Agents (ESA) Dose | Post-Treatment | 16525.8 units/mo | Standard Deviation 16917 |
| Ferric Citrate - Peritoneal Dialysis | Erythropoiesis Stimulating Agents (ESA) Dose | Pre-Treatment | 16724.4 units/mo | Standard Deviation 14042.3 |
| Ferric Citrate - Peritoneal Dialysis | Erythropoiesis Stimulating Agents (ESA) Dose | Post-Treatment | 16780.1 units/mo | Standard Deviation 13433.7 |
Secondary
Intravenous (IV) Iron
The amount of intravenous (IV) iron in mg used per month by participants for 6 months before and 6 months on Ferric Citrate treatment.
Time frame: 6 months
Population: The final analysis included 21 Hemodialysis and 26 Peritoneal Dialysis patients after exclusion of early dropouts. Wilcoxon signed rank test was used to compare pre-treatment and on-treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Citrate - Hemodialysis | Intravenous (IV) Iron | Pre-Treatment | 249.2 mg/mo | Standard Deviation 215.6 |
| Ferric Citrate - Hemodialysis | Intravenous (IV) Iron | On-Treatment | 102 mg/mo | Standard Deviation 137.5 |
| Ferric Citrate - Peritoneal Dialysis | Intravenous (IV) Iron | Pre-Treatment | 21.2 mg/mo | Standard Deviation 43.1 |
| Ferric Citrate - Peritoneal Dialysis | Intravenous (IV) Iron | On-Treatment | 11.6 mg/mo | Standard Deviation 33.7 |
Secondary
Median Pill Count
median pill count of ferric citrate pills/day required to maintain phosphorus control
Time frame: 6 months
Population: The final analysis included 21 Hemodialysis and 26 Peritoneal Dialysis patients after exclusion of early dropouts.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ferric Citrate - Hemodialysis | Median Pill Count | Phosphate binder pill count prior to Ferric Citrate use | 9.5 tablets per day |
| Ferric Citrate - Hemodialysis | Median Pill Count | Phosphate binder pill count during Ferric Citrate use | 6.0 tablets per day |
| Ferric Citrate - Peritoneal Dialysis | Median Pill Count | Phosphate binder pill count prior to Ferric Citrate use | 6 tablets per day |
| Ferric Citrate - Peritoneal Dialysis | Median Pill Count | Phosphate binder pill count during Ferric Citrate use | 4.5 tablets per day |