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

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

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.

Study Overview

• Status: Terminated
• Conditions: Secondary Hyperparathyroidism; Kidney Failure; Hyperphosphatemia; Hypercalcemia
• Intervention / Treatment: Drug: Calcitriol; Drug: Paricalcitol

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calcitriol, then Paricalcitol; 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; 3 times weekly; Other Names: Calcijex®; Drug: Paricalcitol; 3 times weekly; Other Names: Zemplar®
Active Comparator: Paricalcitol, then Calcitriol; 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; 3 times weekly; Other Names: Calcijex®; Drug: Paricalcitol; 3 times weekly; Other Names: Zemplar®

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Winthrop University Hospital
• Investigators: Principal Investigator: Shayan Shirazian, MD, Winthrop University Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: November 7, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (Estimated): November 12, 2012

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Parathyroid Diseases; Calcium Metabolism Disorders; Water-Electrolyte Imbalance; Phosphorus Metabolism Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hyperparathyroidism; Renal Insufficiency; Bone Diseases; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hypercalcemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Calcitriol
• Other Study ID Numbers: 12027