Paricalcitol Improves Anemia of Inflammation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Benefits of the Paricalcitol (Selective Vitamin D Receptor Activator) on Anemia of Inflammation in Dialysis Patients Under Erythropoiesis-stimulating Agents Treatment.

Conditions
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Anemia

Intervention / Treatment
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* Drug: Paricalcitol
* Drug: Epoetin beta
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: paricalcitol plus epoetin beta<br>Paricalcitol 2 capsules /three times per week & epoetin | Drug: Paricalcitol<br>* Paricalcitol 2 capsules/three times per week<br>* Other names: Selective vitamin D receptor activation;Drug: Epoetin beta<br>* epoetin 1-3 times per week<br>* Other names: anti-anemic drug;|
| Placebo Comparator: placebo plus epoetin beta<br>Placebo 2 capsules/three times per week & epoetin | Drug: Epoetin beta<br>* epoetin 1-3 times per week<br>* Other names: anti-anemic drug;Drug: Placebo<br>* Placebo 2 capsules/three times per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ESA dosage | Percentage of ESA doses after 6 months of the paricalcitol or placebo administration. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on ferrokinetics. | Changes on serum iron, transferrin, ferritin, transferrin saturation and red cell distribution width at month 6. | 6 months | 
| Changes on interleukin-6 plasma levels. | Changes on pg/ml | 6 months | 
| Changes on hepcidin plasma levels. | Changes on pg/ml | 6 months | 
| Changes on erythropoietin plasma levels. | Changes on mUI/ml | 6 months | 
| Changes on systolic blood pressure. | Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring. | 6 months | 
| Changes on diastolic blood pressure. | Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring. | 6 months | 
| Cardiovascular serious adverse events in each arm of treatment. | Cardiac arrest, angina pectoris. Stroke. | 6 months | 
| Adverse events related to vascular access disfunction. | Arteriovenous fistula site hemorrhage or thrombosis. Catheter disfunction. | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal disease, Erythropoiesis, Erythropoietin stimulating agent, Iron, Klotho, Selective vitamin D receptor activation