Erythropoietin in Hemolytic Uremic Syndrome

Anemia Clinical Trial

Official title:

Effect of Erythropoietin on Red Blood Cell Requirement in Children With Hemolytic Uremic Syndrome: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03776851
• Other study ID #: 347-HGNPE-2018
• Status: Completed
• Phase: Phase 4
• Start date: January 1, 2019
• Est. completion date: December 30, 2020

Study information

• Verified date: January 2021
• Source: Hospital General de Niños Pedro de Elizalde
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 30, 2020
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Azotemia
• Hemolysis
• Hemolytic-Uremic Syndrome
• Syndrome

Intervention

Drug:
• erythropoietin
erythropoietin 50 International Units (IU) per kilogram three times weekly by subcutaneous route

Locations

Country	Name	City	State
Argentina	HGNPE	Caba

Sponsors (1)

Lead Sponsor	Collaborator
Hospital General de Niños Pedro de Elizalde

Country where clinical trial is conducted

Argentina, 

References & Publications (7)

Ardissino G, Daccò 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. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of RBC transfusions	To determine if administration of erythropoietin decreases the number of RBC during the acute stage of hemolytic uremic syndrome	At the end of the 36 month study recruiting period
Secondary	Erythropoietin levels	To determine if erythropoietin levels correlate with RBC transfusions requirement.	At the end of the 36 month study recruiting period