Clinical trial NCT02876211: Paricalcitol Improves Anemia of Inflammation
Official title: Benefits of the Paricalcitol (Selective Vitamin D Receptor Activator) on Anemia of Inflammation in Dialysis Patients Under Erythropoiesis-stimulating Agents Treatment.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Anemia
Keywords: Renal disease
Erythropoiesis
Erythropoietin stimulating agent
Iron
Klotho
Selective vitamin D receptor activation
Lead sponsor: Hospital Son Espases
Sponsor class: OTHER
First posted: 2016-08-23
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Anemia of inflammation (AI) is a common comorbidity in hemodialysis patients. Paricalcitol is a selective vitamin D receptor activator with potential benefits on anti-inflammatory cytokines expression. The paricalcitol for the secondary hyperparathyroidism control may improve AI decreasing erythropoietin stimulating agents (ESAs) dosage.

Detailed description: Anemia of inflammation and secondary hyperparathyroidism (SHPT) are two common clinical complications in patients with chronic kidney disease. Eryptosis (accelerated red blood cell death) is a novel mechanism associated with renal anemia and several factors such us iron, erythropoietin and klotho (anti-aging hormone) deficiency have been associated with this process.

The use of the paricalcitol may inhibit pro-inflammatory cytokines expression, especially interleukine-6, which is one of the most important cytokine associated with the pathogenesis of the AI. If the use of the paricalcitol for the SHPT control may exert direct influence on the erythropoiesis process is not known.

Eligibility criteria: Inclusion Criteria:

* Age \>= 18 years.
* Patients with CKD on hemodialysis of any etiology..
* Hemoglobin between 9 and 12g/dl at least 12 weeks before enrollment in the study.
* Hemoglobin plasma levels stabilized: Hb variation \<or = 1 g / dl for the two months prior to inclusion in the study.
* Patients with anemia of renal etiology.
* ESA treatment with stable doses for 2 months prior to baseline.Stable dose ESA Definition: Variation \<or = 3000UI/week.
* Iron status: Ferritin\> 200 ng / mL and/or transferrin saturation index (IST):\> = 20%).
* KT / V \>= 1.2 ( Daugirdas-2nd generation).
* Calcium concentrations between : 8.4 to 9.5 mg / dl and phosphorus: 3.5-5.5 mg / dl.
* Vitamin D 25OH normal \>= 15 ng / ml (patients with lower levels will be supplemented with calcifediol 16000 IU / bi-weekly for 6 weeks in selected patients).
* PTHi concentrations\> = 150 pg / mL and \<or = to 300 pg / ml.
* Patients who accept their inclusion in the study and sign informed consent.

Exclusion Criteria:

* Epoetin beta dose \> 18,000 IU / weekly.
* Pregnant woman of childbearing age or gestational wishes or not to use adequate contraception ( the Ogino-Knaus contraceptive method is considered unsuitable).
* Active bleeding episode or history of transfusion the 2 months prior to baseline.
* Patients with non-renal causes of anemia: malignancies, folic acid or vitamin B12 deficiency, hemoglobinopathies, hemolysis, pure red cell aplasia secondary to erythropoietin.
* Patients treated with the selective vitamin D receptor activator in the 3 months prior to inclusion in the study.
* Acute or chronic symptomatic: heart failure (IV-NYHA), infection or inflammatory disease, uncontrolled hypertension that requires the suspension of epoetin beta, thrombocytopathies, aplastic anemia.
* Immunosuppressive treatment with uncontrolled Hemoglobin level
* Allergy to paricalcitol or any of its components.

Primary outcomes:
measure: Changes in ESA dosage
timeFrame: 6 months
Secondary outcomes:
measure: Changes on ferrokinetics.
timeFrame: 6 months
measure: Changes on interleukin-6 plasma levels.
timeFrame: 6 months
measure: Changes on hepcidin plasma levels.
timeFrame: 6 months
measure: Changes on erythropoietin plasma levels.
timeFrame: 6 months
measure: Changes on systolic blood pressure.
timeFrame: 6 months
measure: Changes on diastolic blood pressure.
timeFrame: 6 months
measure: Cardiovascular serious adverse events in each arm of treatment.
timeFrame: 6 months
measure: Adverse events related to vascular access disfunction.
timeFrame: 6 month
Other outcomes:
Locations:
city: Palma de Mallorca
country: Spain
facility: Son Espases University Hospital
state: Islas Baleares
Study officials:
affiliation: Son Espases University Hospital
name: Miguel Uriol, Ph.D.M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sun CC, Vaja V, Babitt JL, Lin HY. Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation. Am J Hematol. 2012 Apr;87(4):392-400. doi: 10.1002/ajh.23110. Epub 2012 Jan 31.
citation: Perlstein TS, Pande R, Berliner N, Vanasse GJ. Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: association with anemia of inflammation. Blood. 2011 Mar 10;117(10):2800-6. doi: 10.1182/blood-2010-09-309708. Epub 2011 Jan 14.
citation: Kempe DS, Ackermann TF, Fischer SS, Koka S, Boini KM, Mahmud H, Foller M, Rosenblatt KP, Kuro-O M, Lang F. Accelerated suicidal erythrocyte death in Klotho-deficient mice. Pflugers Arch. 2009 Jul;458(3):503-12. doi: 10.1007/s00424-009-0636-4. Epub 2009 Jan 28.