Erythropoietin in Hemolytic Uremic Syndrome
Primary Purpose
Hemolytic-Uremic Syndrome, Anemia
Status
Completed
Phase
Phase 4
Locations
Argentina
Study Type
Interventional
Intervention
erythropoietin
Sponsored by
About this trial
This is an interventional supportive care trial for Hemolytic-Uremic Syndrome focused on measuring Hemolytic-Uremic Syndrome, erythropoietin, RBC transfusion
Eligibility Criteria
Inclusion Criteria:
- Post diarrheal HUS: Prodrome of enteritis followed by microangiopathic hemolytic anemia, thrombocytopenia and signs of renal damage (increased plasma creatinine, proteinuria, and / or hematuria). Proven STEC infection wiil not be required to enter into the study.
Exclusion Criteria:
- Atypical HUS
- HUS associated with systemic diseases (pneumococcal infection, HIV, Systemic lupus erythematosus) or drugs
- Anemia or known kidney disease
- Previously transfused or treated with erythropoietin
- Contraindications to erythropoietin
Sites / Locations
- HGNPE
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Erythropoietin
No Intervention
Arm Description
Erythropoietin plus standard of care (RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability)
Standard of care: RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability
Outcomes
Primary Outcome Measures
Number of RBC transfusions
To determine if administration of erythropoietin decreases the number of RBC during the acute stage of hemolytic uremic syndrome
Secondary Outcome Measures
Erythropoietin levels
To determine if erythropoietin levels correlate with RBC transfusions requirement.
Full Information
NCT ID
NCT03776851
First Posted
December 11, 2018
Last Updated
January 11, 2021
Sponsor
Hospital General de Niños Pedro de Elizalde
1. Study Identification
Unique Protocol Identification Number
NCT03776851
Brief Title
Erythropoietin in Hemolytic Uremic Syndrome
Official Title
Effect of Erythropoietin on Red Blood Cell Requirement in Children With Hemolytic Uremic Syndrome: a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
January 1, 2019 (Actual)
Primary Completion Date
December 30, 2020 (Actual)
Study Completion Date
December 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital General de Niños Pedro de Elizalde
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the impact of early administration of erythropoietin in the number of red blood cell transfusions in children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS).
Detailed Description
Introduction:
Anemia in STEC-HUS is treated with red blood cell (RBC) transfusions. It can causes hypervolemia, hyperkalemia, exacerbate the thrombotic state of the disease, transmit infectious agents and trigger antigenic sensitization. Anemia is mainly due to hemolysis, but deficit of erythropoietin synthesis (EPO) may aggravate it. Although recombinant human EPO is frequently used in children with STEC-HUS there is no adequate evidence of its benefit. If it is confirmed that EPO reduce the number of RBC transfusions, its administration could diminish the aforementioned risks and also reduce costs.
Objective:
To determine if EPO administration decreases the number of RBC transfusions and; secondarily, to assess if its levels influence on transfusion requirement.
Methodology:
Randomized, open controlled clinical trial. We will include 28 patients (14 per arm) <18 years with STEC-HUS admitted to our hospital. They will be grouped after randomization:(1) One to standard of care (RBC transfusions with hemoglobin ≤7 mg / dl and/or hemodynamic instability) and (2) the other to standard of care plus EPO (50 u / kg subcutaneous three times weekly) and RBC transfusions with hemoglobin ≤7 mg / dl). Serum EPO will be measured by ELISA and together with the clinical and laboratory variables, association with RBC transfusions number will be sought. Written informed consent and assent when appropriate, will be requested prior to enter into the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemolytic-Uremic Syndrome, Anemia
Keywords
Hemolytic-Uremic Syndrome, erythropoietin, RBC transfusion
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Erythropoietin
Arm Type
Experimental
Arm Description
Erythropoietin plus standard of care (RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability)
Arm Title
No Intervention
Arm Type
No Intervention
Arm Description
Standard of care: RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability
Intervention Type
Drug
Intervention Name(s)
erythropoietin
Other Intervention Name(s)
EPO
Intervention Description
erythropoietin 50 International Units (IU) per kilogram three times weekly by subcutaneous route
Primary Outcome Measure Information:
Title
Number of RBC transfusions
Description
To determine if administration of erythropoietin decreases the number of RBC during the acute stage of hemolytic uremic syndrome
Time Frame
At the end of the 36 month study recruiting period
Secondary Outcome Measure Information:
Title
Erythropoietin levels
Description
To determine if erythropoietin levels correlate with RBC transfusions requirement.
Time Frame
At the end of the 36 month study recruiting period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Post diarrheal HUS: Prodrome of enteritis followed by microangiopathic hemolytic anemia, thrombocytopenia and signs of renal damage (increased plasma creatinine, proteinuria, and / or hematuria). Proven STEC infection wiil not be required to enter into the study.
Exclusion Criteria:
Atypical HUS
HUS associated with systemic diseases (pneumococcal infection, HIV, Systemic lupus erythematosus) or drugs
Anemia or known kidney disease
Previously transfused or treated with erythropoietin
Contraindications to erythropoietin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alejandro Balestracci, MD, PhD
Organizational Affiliation
Hospital General de Niños Pedro de Elizalde
Official's Role
Principal Investigator
Facility Information:
Facility Name
HGNPE
City
Caba
ZIP/Postal Code
1417
Country
Argentina
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The authors will share the generated data with qualified external researchers during the next 5 years after article publication. All data provided will be anonymized to respect the privacy of patients who have participated in the trail in line with applicable laws and regulations.
IPD Sharing Time Frame
During the next 5 years after article publication.
IPD Sharing Access Criteria
Qualified external researchers
Citations:
PubMed Identifier
25149851
Citation
Ardissino G, Dacco V, Testa S, Civitillo CF, Tel F, Possenti I, Belingheri M, Castorina P, Bolsa-Ghiringhelli N, Tedeschi S, Paglialonga F, Salardi S, Consonni D, Zoia E, Salice P, Chidini G. Hemoconcentration: a major risk factor for neurological involvement in hemolytic uremic syndrome. Pediatr Nephrol. 2015 Feb;30(2):345-52. doi: 10.1007/s00467-014-2918-0. Epub 2014 Aug 23.
Results Reference
background
PubMed Identifier
19707787
Citation
Scheiring J, Rosales A, Zimmerhackl LB. Clinical practice. Today's understanding of the haemolytic uraemic syndrome. Eur J Pediatr. 2010 Jan;169(1):7-13. doi: 10.1007/s00431-009-1039-4. Epub 2009 Aug 26.
Results Reference
background
PubMed Identifier
9630043
Citation
Exeni R, Donato H, Rendo P, Antonuccio M, Rapetti MC, Grimoldi I, Exeni A, de Galvagni A, Trepacka E, Amore A. Low levels of serum erythropoietin in children with endemic hemolytic uremic syndrome. Pediatr Nephrol. 1998 Apr;12(3):226-30. doi: 10.1007/s004670050443.
Results Reference
background
PubMed Identifier
21906325
Citation
Moore E, Bellomo R. Erythropoietin (EPO) in acute kidney injury. Ann Intensive Care. 2011 Mar 21;1(1):3. doi: 10.1186/2110-5820-1-3.
Results Reference
background
PubMed Identifier
24005791
Citation
Warady BA, Silverstein DM. Management of anemia with erythropoietic-stimulating agents in children with chronic kidney disease. Pediatr Nephrol. 2014 Sep;29(9):1493-505. doi: 10.1007/s00467-013-2557-x. Epub 2013 Sep 5.
Results Reference
background
PubMed Identifier
19085014
Citation
Pape L, Ahlenstiel T, Kreuzer M, Drube J, Froede K, Franke D, Ehrich JH, Haubitz M. Early erythropoietin reduced the need for red blood cell transfusion in childhood hemolytic uremic syndrome: a randomized prospective pilot trial. Pediatr Nephrol. 2009 May;24(5):1061-4. doi: 10.1007/s00467-008-1087-4. Epub 2008 Dec 16.
Results Reference
background
PubMed Identifier
25138373
Citation
Balestracci A, Martin SM, Toledo I, Alvarado C, Wainsztein RE. Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control study. Pediatr Nephrol. 2015 Feb;30(2):339-44. doi: 10.1007/s00467-014-2911-7. Epub 2014 Aug 21.
Results Reference
background
PubMed Identifier
35166922
Citation
Balestracci A, Capone MA, Meni Battaglia L, Toledo I, Martin SM, Beaudoin L, Balbaryski J, Gomez L. Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial. Pediatr Nephrol. 2022 Oct;37(10):2383-2392. doi: 10.1007/s00467-022-05474-9. Epub 2022 Feb 15.
Results Reference
derived
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Erythropoietin in Hemolytic Uremic Syndrome
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