Paricalcitol Effect on Anemia in CKD

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Direct Effect of Paricalcitol on Anemia in Chronic Kidney Disease

Conditions
-----------------
Anemia, Chronic Kidney Disease

Intervention / Treatment
-----------------
* Drug: Paricalcitol
* Drug: Calcitriol


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>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<br>* Rocaltrol cp 0,5 mcg every other day per os<br>* Other names: Rocaltrol;|
| Experimental: Paricalcitol<br>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<br>* Zemplar cp 1 mcg/day per os<br>* Other names: Zemplar;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modification in hemoglobin levels |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modifications in urinary protein excretion |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anemia, chronic kidney disease, vitamin D, paricalcitol, hyperparathyroidism