Management of Mineral and Bone Disease in Hemodialysis-Calcitriol vs. Paricalcitol

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Prospective, Cross-Over Study of Calcitriol vs. Paricalcitol in the Treatment of Mineral and Bone Disease in Hemodialysis Patients

Conditions
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Kidney Failure, Secondary Hyperparathyroidism, Hyperphosphatemia, Hypercalcemia

Intervention / Treatment
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* Drug: Calcitriol
* Drug: Paricalcitol


Participation Criteria
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Eligibility Criteria
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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: age greater than 18 active malignancy expected survival greater than 6 months high likelihood of renal transplant during the study period. Low calcium bath prior parathyroidectomy use of calcimimetics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcitriol, then Paricalcitol<br>Patients randomized to an active vitamin D treatment protocol based on IV calcitriol. After 14 weeks, patients cross-over to an active vitamin D protocol based on IV paricalcitol for 14 weeks. | Drug: Calcitriol<br>* 3 times weekly<br>* Other names: Calcijex®;Drug: Paricalcitol<br>* 3 times weekly<br>* Other names: Zemplar®;|
| Active Comparator: Paricalcitol, then Calcitriol<br>Patients randomized to an active vitamin D treatment protocol based on IV paricalcitol. After 14 weeks, patients cross-over to an active vitamin D protocol based on IV calcitriol for 14 weeks. | Drug: Calcitriol<br>* 3 times weekly<br>* Other names: Calcijex®;Drug: Paricalcitol<br>* 3 times weekly<br>* Other names: Zemplar®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTH Levels at Month 3 Post Calcitriol Treatment Initiation |  | Up to Month 6 | 
| PTH Levels at Month 3 Post Paricalcitol Treatment Initiation |  | Up to Month 6 | 
| Phosphorus Levels at Month 3 Post Calcitriol Initiation |  | Up to Month 6 | 
| Phosphorus Levels at 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 | 
| Amount of Active Vitamin D Analog Used Through Month 3 Post Paricalcitol Initiation |  | Up to Month 6 |