Paricalcitol Improves Anemia of Inflammation

Anemia Clinical Trial

— PIERAID  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02876211
• Other study ID #: PIERAID-2013
• Status: Recruiting
• Phase: Phase 4
• Start date: December 2014
• Est. completion date: December 2024

Study information

• Verified date: August 2022
• Source: Hospital Son Espases
• Contact: Miguel Uriol, Ph.D.M.D.
• Phone: 00-34-871-205000
• Email: miguelg.uriol[@]ssib.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: December 2024
• Est. primary completion date: August 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Inflammation

Intervention

Drug:
• Paricalcitol
Paricalcitol 2 capsules/three times per week
• Epoetin beta
epoetin 1-3 times per week
• Placebo
Placebo 2 capsules/three times per week

Locations

Country	Name	City	State
Spain	Son Espases University Hospital	Palma de Mallorca	Islas Baleares

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Son Espases

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Kempe DS, Ackermann TF, Fischer SS, Koka S, Boini KM, Mahmud H, Föller 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in ESA dosage	Percentage of ESA doses after 6 months of the paricalcitol or placebo administration.	6 months
Secondary	Changes on ferrokinetics.	Changes on serum iron, transferrin, ferritin, transferrin saturation and red cell distribution width at month 6.	6 months
Secondary	Changes on interleukin-6 plasma levels.	Changes on pg/ml	6 months
Secondary	Changes on hepcidin plasma levels.	Changes on pg/ml	6 months
Secondary	Changes on erythropoietin plasma levels.	Changes on mUI/ml	6 months
Secondary	Changes on systolic blood pressure.	Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring.	6 months
Secondary	Changes on diastolic blood pressure.	Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring.	6 months
Secondary	Cardiovascular serious adverse events in each arm of treatment.	Cardiac arrest, angina pectoris. Stroke.	6 months
Secondary	Adverse events related to vascular access disfunction.	Arteriovenous fistula site hemorrhage or thrombosis. Catheter disfunction.	6 month