Pure Red Cell Aplasia in Patients With Chronic Kidney Disease and in Use of Epoetin Alfa

Research of Pure Red Cell Aplasia in Patients With Chronic Kidney Disease and in Use of Epoetin Alfa Produced by Immunobiological Technology Institute (Bio-Manguinhos) From Oswaldo Cruz Foundation (Bio-Manguinhos / Fiocruz)

The purpose of this study is to determine occurrence of pure red cell aplasia in a group of participants with chronic renal insufficiency and with resistance criteria to epoetin alfa treatment.The investigational product is producted by Bio-Manguinhos / Fiocruz (BIO-EPO) and it is provided by the Unified Health System.

Study Overview

• Status: Unknown
• Conditions: Renal Insufficiency, Chronic; Red-Cell Aplasia, Pure
• Intervention / Treatment: Procedure: Pure Red Cell Aplasia diagnostic confirmation

• Study Type: Interventional
• Enrollment (Anticipated): 531
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Use of alfa epoetin manufactured by Bio-Manguinhos for at least 8 weeks before the moment of hyporesponsiveness diagnosis;
• Nonuse of alfa epoetin from another manufacturer for at least 24 weeks before hyporesponsiveness diagnosis;
• Presence of the criteria for pure red cell aplasia disease, which is absence of a significant reduction in serum levels of leukocytes and platelets.

Exclusion Criteria:

The screened patients who have at least one of the following criteria will be excluded from the study, and it may be replaced by another participant for the research.

• if there is no legal representative, an intellectual disability that restrain the compliance and signature of informed consent,
• no agreement assigning the informed consent;
• It will be excluded from the study if from the moment of hyporesponsiveness diagnosis the participant have: lactation pregnancy, hypersensitivity or intolerance previously known for alfa epoetin or one of its components, intolerance or allergy to parenteral iron, acute hemorrhage, kidney transplantation, hemolysis defined as the presence of anemia associated with high levels of indirect bilirubin and lactate dehydrogenase , percentage of reticulocytes> 1.5% absolute reticulocyte> 75,000 / microliter.
• deficiency of folate and / or vitamin B12.
• pancytopenia.
• in use with medications known to cause anemia and / or pure red cell aplasia as: Valproic Acid; Azathioprine; Chloramphenicol; Phenytoin; Isoniazid; Mycophenolate mofetil.
• presence of the following comorbidities: Diabetes mellitus; epilepsy; chronic viral hepatitis; secondary hyperparathyroidism uncontrolled; hypertension systolic; inflammation (acute or chronic); myelofibrosis; myelodysplasia; neoplasm and thalassemias;
• severe disease in the 24 weeks before the hyporesponsiveness diagnosis; including: stroke, septic shock, thromboembolic events; acute myocardial infarction
• lack of information or damage to quality data that avoid disease classification as a case of hyporesponsiveness.
• Immunoglobulin M and Immunoglobulin M serology for Parvovirus B19, Epstein-Barr and Cytomegalovirus.
• serology for HIV in the last 12 months.
• established immunological disease.
• dosage of protein C-reactive titrated .
• presence of antinuclear antibody and rheumatoid factor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Pure red cell aplasia participants; Group of participants with pure red cell aplasia and chronic kidney disease, that have resistance criteria to treatment with epoetin alfa produced by Bio-Manguinhos / Fiocruz. The Patients who meet the appropriate criteria in the selection period will be subject to Pure Red Cell Aplasia diagnostic confirmation.

Procedure: Pure Red Cell Aplasia diagnostic confirmation; Patients who meet the appropriate criteria in the selection period will be subject to Pure Red Cell Aplasia diagnostic confirmation by collecting 20 mL of blood in dialysis units. The samples will be processed, aliquoted and transported to Bio-Manguinhos, where depart periodically (according to the volume of samples) to the reference laboratory Sce Immunologie et d'Hématologie biologiques Hôpital Saint Antoine, where the dosage of antibody will be held anti epoetin alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Hyporesponsiveness to EPO related to anti-alfa epoetin antibodies.	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum levels of leukocytes and platelets correlated with anti-alfa epoetin antibodies	3 years
Anti-alfa epoetin antibodies titers related to Hemoglobin levels	3 years
Hemoglobin levels related to alfa epoetin dosage	3 years
Percentage anti-alfa epoetin neutralizing antibodies related to Hemoglobin levels	3 years

Collaborators and Investigators

• Sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
• Investigators: Principal Investigator: Vivian Rotman, M.D., Biomanguinhos

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: January 5, 2016
• First Submitted That Met QC Criteria: January 5, 2016
• First Posted (Estimate): January 6, 2016

Study Record Updates

• Last Update Posted (Estimate): January 6, 2016
• Last Update Submitted That Met QC Criteria: January 5, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Anemia; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Red-Cell Aplasia, Pure
• Other Study ID Numbers: ASCLIN 004/2014