Back to resultsParicalcitol Improves Anemia of Inflammation (PIERAID)
Primary Purpose
Anemia
Status
Recruiting
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Paricalcitol
Epoetin beta
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Anemia focused on measuring Renal disease, Erythropoiesis, Erythropoietin stimulating agent, Iron, Klotho, Selective vitamin D receptor activation
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.
Sites / Locations
- Son Espases University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
paricalcitol plus epoetin beta
placebo plus epoetin beta
Arm Description
Paricalcitol 2 capsules /three times per week & epoetin
Placebo 2 capsules/three times per week & epoetin
Outcomes
Primary Outcome Measures
Changes in ESA dosage
Percentage of ESA doses after 6 months of the paricalcitol or placebo administration.
Secondary Outcome Measures
Changes on ferrokinetics.
Changes on serum iron, transferrin, ferritin, transferrin saturation and red cell distribution width at month 6.
Changes on interleukin-6 plasma levels.
Changes on pg/ml
Changes on hepcidin plasma levels.
Changes on pg/ml
Changes on erythropoietin plasma levels.
Changes on mUI/ml
Changes on systolic blood pressure.
Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring.
Changes on diastolic blood pressure.
Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring.
Cardiovascular serious adverse events in each arm of treatment.
Cardiac arrest, angina pectoris. Stroke.
Adverse events related to vascular access disfunction.
Arteriovenous fistula site hemorrhage or thrombosis. Catheter disfunction.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02876211
Brief Title
Paricalcitol Improves Anemia of Inflammation
Acronym
PIERAID
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
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2014 (Actual)
Primary Completion Date
August 2022 (Actual)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Son Espases
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia
Keywords
Renal disease, Erythropoiesis, Erythropoietin stimulating agent, Iron, Klotho, Selective vitamin D receptor activation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
paricalcitol plus epoetin beta
Arm Type
Experimental
Arm Description
Paricalcitol 2 capsules /three times per week & epoetin
Arm Title
placebo plus epoetin beta
Arm Type
Placebo Comparator
Arm Description
Placebo 2 capsules/three times per week & epoetin
Intervention Type
Drug
Intervention Name(s)
Paricalcitol
Other Intervention Name(s)
Selective vitamin D receptor activation
Intervention Description
Paricalcitol 2 capsules/three times per week
Intervention Type
Drug
Intervention Name(s)
Epoetin beta
Other Intervention Name(s)
anti-anemic drug
Intervention Description
epoetin 1-3 times per week
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 2 capsules/three times per week
Primary Outcome Measure Information:
Title
Changes in ESA dosage
Description
Percentage of ESA doses after 6 months of the paricalcitol or placebo administration.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Changes on ferrokinetics.
Description
Changes on serum iron, transferrin, ferritin, transferrin saturation and red cell distribution width at month 6.
Time Frame
6 months
Title
Changes on interleukin-6 plasma levels.
Description
Changes on pg/ml
Time Frame
6 months
Title
Changes on hepcidin plasma levels.
Description
Changes on pg/ml
Time Frame
6 months
Title
Changes on erythropoietin plasma levels.
Description
Changes on mUI/ml
Time Frame
6 months
Title
Changes on systolic blood pressure.
Description
Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring.
Time Frame
6 months
Title
Changes on diastolic blood pressure.
Description
Changes in mmHg determined by 24 hours ambulatory blood pressure monitoring.
Time Frame
6 months
Title
Cardiovascular serious adverse events in each arm of treatment.
Description
Cardiac arrest, angina pectoris. Stroke.
Time Frame
6 months
Title
Adverse events related to vascular access disfunction.
Description
Arteriovenous fistula site hemorrhage or thrombosis. Catheter disfunction.
Time Frame
6 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Miguel Uriol, Ph.D.M.D.
Phone
00-34-871-205000
Ext
75212
Email
miguelg.uriol@ssib.es
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miguel Uriol, Ph.D.M.D.
Organizational Affiliation
Son Espases University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Son Espases University Hospital
City
Palma de Mallorca
State/Province
Islas Baleares
ZIP/Postal Code
07120
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miguel Uriol, Ph.D.M.D.
Phone
00-34-871205000
Ext
75212
Email
miguelg.uriol@ssib.es
First Name & Middle Initial & Last Name & Degree
Sheila Cabello Pelegrin, MD
First Name & Middle Initial & Last Name & Degree
Juan Rey Valeriano, MD
First Name & Middle Initial & Last Name & Degree
Antonio Corral Paez, MD
First Name & Middle Initial & Last Name & Degree
Angel Garcia Alvarez, Pharmacist
First Name & Middle Initial & Last Name & Degree
Sonia Jimenez Mendoza, MD
First Name & Middle Initial & Last Name & Degree
Manuel Luque_Ramírez, Ph.D.MD.
First Name & Middle Initial & Last Name & Degree
Miguel Uriol Rivera, Ph.D.MD.
First Name & Middle Initial & Last Name & Degree
Aina Obrador Mulet, MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The IPD could be shared with any interested public research institute
IPD Sharing Time Frame
After finalized the study
IPD Sharing Access Criteria
Research
Citations:
PubMed Identifier
22290531
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.
Results Reference
background
PubMed Identifier
21239700
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.
Results Reference
background
PubMed Identifier
19184092
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.
Results Reference
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Paricalcitol Improves Anemia of Inflammation
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