Paricalcitol Effect on Anemia in CKD

Direct Effect of Paricalcitol on Anemia in Chronic Kidney Disease

Current activated Vitamin D therapies are approved for treating secondary hyperparathyroidism in chronic kidney disease (CKD), and a large body of experimental data in animals confirms the effects of Vitamin D that extend beyond mineral metabolism. Several studies show that the benefits are greater with the newer vitamin D analog paricalcitol when compared with calcitriol. A large gap exists in our knowledge between epidemiological studies in human that demonstrate improved outcomes with vitamin D use and observations in preclinical studies demonstrating the pleiotropic effects of Vitamin D. To explore the provenance of epidemiological outcomes in CKD, we conducted a pilot randomized trial to determine whether the use of paricalcitol, compared to calcitriol, leads to improvement in anemia, a marker associated with worse outcomes in chronic kidney disease, and whether this effect not only reflects the hyperparathyroidism correction, but is also dependent on the direct effects of paricalcitol on erythroid progenitor cells.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease
• Intervention / Treatment: Drug: Calcitriol; Drug: Paricalcitol

Detailed Description

To better understand the direct effects of paricalcitol on anemia in patients with chronic kidney disease (stage 3-5), we conducted a pilot trial in 60 patients who were randomly allocated equally to 2 groups to receive or not paricalcitol orally for 6 months.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80129
    • Federico II University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• age > 18
• written informed consent
• CKD stage 3-5 (eGFR <60 ml/min/1,73 m2)
• PTH 30-300 pg/ml
• Hb <10 g/dl >3 consecutive months
• Ferritin > 100 ng/ml
• transferrin saturation (TSAT) 20-40%
• mean corpuscular volume (MCV) 85-95%
• for patients treated with Ace-inhibitors or angiotensin receptor blockers, dose stable >3 months
• for patients treated with erythropoiesis-stimulating agents (ESA), dose stable >3 months

Exclusion criteria:

• anemia due to non renal cause
• presence of malignancies, inflammatory or infectious disease >3 months
• pregnancy
• bleeding >6 months
• C-reactive protein (CRP) >1 mg/dl
• poorly controlled hypertension (PAS > 170 mmHG and PAD >100 mmHg)
• severe malnutrition
• hypercalcemia (>10,5 mg/dl)
• hyperphosphatemia (>5,5 mg/dl)
• surgical interventions >3 months
• acute myocardial infarction, unstable angina, stroke or transitory ischemic attack, deep venous or pulmonary thromboembolism, congestive heart failure >3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Patients receiving treatment for secondary hyperparathyroidism with calcitriol. The calcitriol dosage schedule provided for an initial dose of 0.5 mch every other day and titration was performed on the basis of the serum levels of intact PTH (iPTH) (target 150-300 pg/mL), Ca, P and Ca x P product as suggested by the US National Kidney Foundation Dialysis outcomes Quality Initiative (NKF-DOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.	Drug: Calcitriol; Rocaltrol cp 0,5 mcg every other day per os; Other Names: Rocaltrol
Experimental: Paricalcitol; Patients treated by Paricalcitol for hyperparathyroidism. The paricalcitol initial dose was 1 mcg/die, and titration was performed on the basis of the serum levels of iPTH, Ca, P and Ca x P product as suggested by the NKF-DOQI and KDIGO guidelines.	Drug: Paricalcitol; Zemplar cp 1 mcg/day per os; Other Names: Zemplar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Modification in hemoglobin levels	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Modifications in urinary protein excretion	6 months

Collaborators and Investigators

• Sponsor: Federico II University
• Investigators: Principal Investigator: Eleonora Riccio, MD

Publications and helpful links

General Publications

• Riccio E, Sabbatini M, Bruzzese D, Capuano I, Migliaccio S, Andreucci M, Pisani A. Effect of paricalcitol vs calcitriol on hemoglobin levels in chronic kidney disease patients: a randomized trial. PLoS One. 2015 Mar 17;10(3):e0118174. doi: 10.1371/journal.pone.0118174. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: January 13, 2013
• First Submitted That Met QC Criteria: January 13, 2013
• First Posted (Estimate): January 15, 2013

Study Record Updates

• Last Update Posted (Estimate): July 30, 2014
• Last Update Submitted That Met QC Criteria: July 29, 2014
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: anemia; chronic kidney disease; vitamin D; paricalcitol; hyperparathyroidism
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; 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: PCX1234; paranemia (Other Identifier: Federico II University of Naples)