Paricalcitol Effect on Anemia in CKD

Sponsor

Federico II University (Other)

Overall Status

Completed

CT.gov ID

NCT01768351

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia Chronic Kidney Disease	Drug: Paricalcitol Drug: Calcitriol	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Direct Effect of Paricalcitol on Anemia in Chronic Kidney Disease

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Mar 1, 2011

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Modification in hemoglobin levels [6 months]

Secondary Outcome Measures

Modifications in urinary protein excretion [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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