Hypercalcemia, Hyperphosphatemia, Kidney Failure, Secondary Hyperparathyroidism
Conditions
Brief summary
The purpose of this non-inferiority study is to compare the safety and effectiveness of a mineral and bone disease treatment protocol based on calcitriol to one based on paricalcitol in hemodialysis patients using revised Kidney Disease: Improving Global Outcomes (KDIGO) parathyroid hormone targets.
Detailed description
Active vitamin D analogs have been the mainstay of treatment for patients on hemodialysis with mineral and bone disease (MBD) for the past decade. Intravenous calcitriol is an active vitamin D analog which is nearly identical to natural 1, 25 Vitamin D3. Calcitriol results from the hydroxylation of previtamin D3 in the liver and kidney. Paricalcitol, 19-nor-1 , 25-dihydroxyvitamin D2, is a newer agent vitamin D analog. This agent is believed to have an effect more specific to the parathyroid gland, and less specific to absorption of calcium and phosphorus from the gut. Although both formulations appear equally effective in suppressing parathyroid hormone (PTH), studies have suggested a greater calcemic effect with intravenous calcitriol as compared to paricalcitol (1). Due to this, paricalcitol is the predominant active vitamin D analog used in hemodialysis patients in the United States. Two recent changes in the management of hemodialysis patients will likely reduce the amount of active vitamin D analogs used in the near future: the liberalization of PTH goals according to international guidelines, (2) and the implementation of bundled payments for dialysis by Medicare. These changes challenge previous studies that have analyzed the safety and efficacy of these medications. The purpose of this prospective, randomized, cross-over study will be to determine whether calcitriol is as safe and effective as paricalcitol in the treatment of MBD in hemodialysis patients using the revised KDIGO parathyroid hormone targets. Our hypothesis is that calcitriol will be as equally safe and effective as paricalcitol in the treatment of MBD in hemodialysis patients.
Interventions
DRUGCalcitriol
3 times weekly
DRUGParicalcitol
3 times weekly
Sponsors
Winthrop University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- All subjects will have been treated for at least three months on hemodialysis with IV paricalcitol. These subjects must have a most recent calcium level within the normal range, most recent phosphorus level \< 8 mg/dL and a most recent PTH between 130-585 pg/mL
Exclusion criteria
Patients will be excluded if: 1. age greater than 18 2. active malignancy 3. expected survival greater than 6 months 4. high likelihood of renal transplant during the study period. 5. Low calcium bath 6. prior parathyroidectomy 7. use of calcimimetics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Calcium Levels at Month 3 Post Calcitriol Treatment Initiation | Up to Month 6 |
| Calcium Levels at Month 3 Post Paricalcitol Treatment Initiation | Up to Month 6 |
Secondary
| Measure | Time frame |
|---|---|
| Phosphorus Levels at Month 3 Post Calcitriol Initiation | Up to Month 6 |
| Phosphorus Levels at Month 3 Post Paricalcitol Initiation | Up to Month 6 |
| PTH Levels at Month 3 Post Calcitriol Treatment Initiation | Up to Month 6 |
| Amount of Active Vitamin D Analog Used Through Month 3 Post Paricalcitol Initiation | Up to Month 6 |
| Amount of Active Vitamin D Analog Used Through Month 3 Post Calcitriol Initiation | Up to Month 6 |
| PTH Levels at Month 3 Post Paricalcitol Treatment Initiation | Up to Month 6 |
Countries
United States
Participant flow
Pre-assignment details
Of the 16 enrolled participants, 3 were removed due to screen failure and 1 patient experienced death before the start of study.
Participants by arm
| Arm | Count |
|---|---|
| Total Participants Who Completed Trial Participants (n=9) who completed the trial. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Kidney Transplant | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total Participants Who Completed Trial |
|---|---|
| Age, Continuous | 74.11 years STANDARD_DEVIATION 5.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 1 / 9 | 2 / 9 |
Outcome results
Primary
Calcium Levels at Month 3 Post Calcitriol Treatment Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | Calcium Levels at Month 3 Post Calcitriol Treatment Initiation | 8.78 mg/dl | Standard Deviation 0.332 |
Primary
Calcium Levels at Month 3 Post Paricalcitol Treatment Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | Calcium Levels at Month 3 Post Paricalcitol Treatment Initiation | 8.6 mg/dl | Standard Deviation 0.3 |
Secondary
Amount of Active Vitamin D Analog Used Through Month 3 Post Calcitriol Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | Amount of Active Vitamin D Analog Used Through Month 3 Post Calcitriol Initiation | 36.9 mcg | Standard Deviation 34.18 |
Secondary
Amount of Active Vitamin D Analog Used Through Month 3 Post Paricalcitol Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | Amount of Active Vitamin D Analog Used Through Month 3 Post Paricalcitol Initiation | 134.6 mcg | Standard Deviation 87.35 |
Secondary
Phosphorus Levels at Month 3 Post Calcitriol Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | Phosphorus Levels at Month 3 Post Calcitriol Initiation | 4.09 mg/dl | Standard Deviation 0.71 |
Secondary
Phosphorus Levels at Month 3 Post Paricalcitol Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | Phosphorus Levels at Month 3 Post Paricalcitol Initiation | 4.45 mg/dl | Standard Deviation 1.18 |
Secondary
PTH Levels at Month 3 Post Calcitriol Treatment Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | PTH Levels at Month 3 Post Calcitriol Treatment Initiation | 309.58 pg/dl | Standard Deviation 183.33 |
Secondary
PTH Levels at Month 3 Post Paricalcitol Treatment Initiation
Time frame: Up to Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | PTH Levels at Month 3 Post Paricalcitol Treatment Initiation | 332.83 pg/dl | Standard Deviation 146.9 |