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Red Blood Cell - IMProving trAnsfusions for Chronically Transfused Recipients (RBC-IMPACT)

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ClinicalTrials.gov Identifier: NCT05255445
Recruitment Status : Recruiting
First Posted : February 24, 2022
Last Update Posted : March 21, 2022
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Westat

Brief Summary:
Red Blood Cell - IMProving trAnsfusions for Chronically Transfused recipients (RBC-IMPACT) is an observational cohort study to assess donor, component, and recipient factors that contribute to RBC efficacy in chronically and episodically transfused patients. The objective of the study is to determine how specific genetic and non-genetic factors in donors and recipients may impact RBC survival after transfusion - in short, what factors on both the donor and recipient side may improve the efficacy of the transfusion.

Condition or disease Intervention/treatment
Sickle Cell Disease Thalassemia Pediatric Cancer Biological: Red Blood Cell (RBC) Transfusion

Detailed Description:
Sickle cell disease (SCD) and thalassemia are genetic disorders inducing anemia of differing pathophysiology. A primary therapy for preventing certain SCD complications (e.g., stroke) and for thalassemia major is regular red blood cell (RBC) transfusion, coupled with iron chelation to prevent the complications of transfusion-induced iron overload. For patients with pediatric hematology-oncology diagnoses with chemotherapy-induced aplasia, RBC transfusion is also common, but the degree of transfusion-induced iron overload and its implications for these patients is incompletely understood. Because iron-related tissue toxicity is a major cause of morbidity and mortality in regularly transfused patients, developing strategies to minimize iron loading and iron toxicity is a key objective of this proposal (study Aim #2), stemming from the objective to optimize RBC unit characteristics that patients with SCD and thalassemia receive beyond RBC phenotype matching for Rh C, E and K antigens (study Aim #1). The study will enroll patients with SCD, thalassemia or pediatric oncologic diagnoses receiving eligible transfusion at 6 hospital sites in the United States, as well as patients with SCD at 5 hemocenters in Brazil.

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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Red Blood Cell - IMProving trAnsfusions for Chronically Transfused Recipients (RBC-IMPACT)
Actual Study Start Date : March 16, 2022
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2025


Group/Cohort Intervention/treatment
Sickle cell disease (SCD)
Patients with SCD who are chronically transfused (in the U.S. and Brazil)
Biological: Red Blood Cell (RBC) Transfusion
Simple RBC transfusion

Thalassemia
Patients with thalassemia who are chronically transfused in the U.S.
Biological: Red Blood Cell (RBC) Transfusion
Simple RBC transfusion

Pediatric Hematology-Oncology
Patients in U.S. with pediatric oncologic diagnoses with hypo-proliferative bone marrow requiring single unit red blood cell transfusion
Biological: Red Blood Cell (RBC) Transfusion
Simple RBC transfusion

Blood Donors
Allogenic blood donors in the US (estimated: 10,200) and allogenic blood donors in Brazil (estimated: 2,100) with extended donation genotyping using an investigational hematology array.



Primary Outcome Measures :
  1. Change in Hemoglobin A or Hemoglobin Level per day (RBC Survival) [ Time Frame: Baseline (immediately pre-) to post-transfusion over 2 years ]
    Change in hemoglobin A or hemoglobin level per day in between subsequent transfusion episodes, for sickle cell disease and thalassemia cohorts, respectively

  2. Change in Serum Iron Level [ Time Frame: Baseline (immediately before) and 2-hours after transfusion ]
    For all groups participating, change in serum iron measured from immediately prior to 2 hours post-transfusion


Secondary Outcome Measures :
  1. Hemoglobin Increment [ Time Frame: Baseline (immediately pre-) to post-transfusion, over 2 years ]
    Hemoglobin increment [defined as Hb/HbA(post-transfusion)visit(i) - Hb/HbA(pre-transfusion)visit(i)] is associated with "RBC survival"

  2. Hemolysis Parameter Increment [ Time Frame: Baseline (immediately pre-) to post-transfusion or 2-hours post-transfusion, over 2 years ]
    Includes serum iron, indirect bilirubin, or plasma free hemoglobin

  3. Hepcidin Level [ Time Frame: Baseline (immediately before) to 2 hours after transfusion ]
    Hepcidin level at time of transfusion is a predictor of change in iron parameters (i.e., transferrin saturation, serum iron) following transfusion

  4. Non-Transferrin-Bound Iron (NTBI) Level [ Time Frame: Baseline (immediately before) to 2 hours after transfusion ]
    NTBI levels in patients with pediatric oncologic diagnoses with aplasia are elevated at baseline and increase following transfusion

  5. Number of Clinical Complications [ Time Frame: 2 years ]
    Increased NTBI, serum iron, or transferrin saturation following transfusion is associated with increased risk of clinical adverse effects (i.e., new infections, SCD complications)


Other Outcome Measures:
  1. Rate of Alloimmunization [ Time Frame: 2 years ]
    Rate of new alloantibody formation

  2. 4-hydroxynonenal [4-HNE] [ Time Frame: 2 years ]
    Recipient oxidative stress pre-transfusion is associated with "RBC survival"

  3. Type I interferon (i.e., MxA protein assay) and other cytokines (i.e., IL-6, MCP-1, IFNgamma) [ Time Frame: 2 years ]
    Recipient inflammation pre-transfusion is associated with "RBC survival"

  4. Number of Transfusion Reactions [ Time Frame: 2 years ]
    Transfusion reactions are associated with "RBC survival"


Biospecimen Retention:   Samples Without DNA

Specimens to be stored for future use from enrolled red cell transfusion recipients include whole blood, plasma and serum.

The study will also retain a sample of packed RBCs from the transfused RBC unit, and a retention tube from the donor of that transfused unit (to be used for extended genotyping but not retained in a long-term biorepository).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All transfused patients with sickle cell disease (in the U.S or Brazil) and thalassemia on simple chronic transfusion from hospitals affiliated with REDS-IV-P Domestic hubs or Brazil hemocenters. (Aim #1)

Chronically transfused patients with sickle cell disease or thalassemia, and patients with pediatric oncology diagnoses with hypo-proliferative bone marrow receiving care at hospitals affiliated with REDS-IV-P Domestic hubs or Brazil hemocenters (for SCD only). (Aim #2).

Criteria

Inclusion Criteria (Aim #1):

  • Well-characterized transfusion-dependent form of SCD or thalassemia (including Hemoglobin E-thalassemia and sickle-beta thalassemia) on chronic simple transfusion therapy
  • On a regular simple RBC transfusion schedule (i.e., 1-3 units scheduled every 2-6 weeks and on a minimum 6-month chronic transfusion trial)
  • Seen at any participating domestic hub hospital (i.e., Columbia University Irving Medical Center/Morgan Stanley Children's Hospital of New York, Weill Cornell Medical Center/Komansky Children's Hospital, Boston Children's Hospital, Froedtert & Medical College of Wisconsin/Children's Wisconsin, University of California San Francisco, Benioff Children's Hospital Oakland) or enrolled in the Brazil REDS-IV-P sickle cell disease cohort and seen at any participating Brazil hemocenter (i.e., Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, HEMOAM - Amazonas, HEMOMINAS - Minas Gerais, HEMOPE -Pernambuco, and HEMORIO - Rio de Janeiro)

Exclusion Criteria (Aim #1):

  • Institutionalization or imprisonment
  • Foster care

Inclusion criteria (Aim #2):

  • Either included in Aim #1 (consented patient with SCD or thalassemia) or patient with pediatric oncologic diagnosis under care in a pediatric hematology/oncology service with anemia due to chemotherapy or primary/secondary hypo-proliferative bone marrow requiring a RBC transfusion (including HSCT)
  • [In domestic study only] Age ≤21 years old (many pediatric services include care of patients up to age 21, therefore the protocol will not limit by age but instead on whether they are seen in a pediatric service)
  • Planned transfusion of RBC from an aliquot or unit from a single donor
  • Seen at any participating domestic hub hospital (i.e., Columbia University Irving Medical Center/Morgan Stanley Children's Hospital of New York, Weill Cornell Medical Center/Komansky Children's Hospital, Boston Children's Hospital, Froedtert & Medical College of Wisconsin/Children's Wisconsin, University of California San Francisco, Benioff Children's Hospital Oakland) or at any REDS-IV-P participating Brazil hemocenter (i.e., Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, HEMOAM - Amazonas, HEMOMINAS - Minas Gerais, HEMOPE -Pernambuco, and HEMORIO - Rio de Janeiro).

Exclusion criteria (Aim #2):

  • Institutionalization or imprisonment
  • Foster care
  • Current active auto-immune hemolytic anemia based on positive direct antiglobulin test (DAT) with laboratory evidence of hemolysis and increased transfusion requirement
  • [In domestic study only] Microangiopathic hemolytic anemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05255445


Contacts
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Contact: Kathy Chapman, MT 301-738-3697 KathyChapman@westat.com
Contact: Sunitha Mathew, MPH 301-294-4472 SunithaMathew@westat.com

Locations
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United States, California
UCSF Benioff Children's Hospital Recruiting
Oakland, California, United States, 94609
Contact: Shannon Kelly, MD       shannon.kelly@ucsf.edu   
Vitalant Research Institute Not yet recruiting
San Francisco, California, United States, 94118
Contact: Brian Custer, PhD, MPH       bcuster@vitalant.org   
United States, Massachusetts
Boston Children's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: John Manis, MD       john.manis@childrens.harvard.edu   
United States, New York
Weill Cornell Medical Collection (WCMC)/New York Presbyterian Hospital (NYPH) Not yet recruiting
New York, New York, United States, 10021
Contact: Melissa Cushing, MD       mec2013@med.cornell.edu   
Columbia University Irving Medical Center/New York Presbyterian Hospital (NYPH) Not yet recruiting
New York, New York, United States, 10032
Contact: Eldad A Hod, MD       eh2217@cumc.columbia.edu   
New York Blood Center (NYBC) Not yet recruiting
New York, New York, United States, 10065
Contact: Bruce Sachais, MD, PhD       bsachais@nybc.org   
United States, Wisconsin
Children's Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Brian Branchford, MD       bbranchford@versiti.org   
Froedtert Hospital Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Lisa Baumann Kreuziger, MD, MS       lisakreuziger@versiti.org   
Versiti Wisconsin, Inc. Not yet recruiting
Milwaukee, Wisconsin, United States, 53233
Contact: Alan Mast, MD, PhD       aemast@versiti.org   
Brazil
HEMOAM - Amazonas Not yet recruiting
Manaus, Amazonas, Brazil, 69050-001
Contact: Nelson A Fraiji, MD, PhD       nfraiji@hemoam.am.gov.br   
HEMOMINAS - Minas Gerais Not yet recruiting
Belo Horizonte, Minas Gerais, Brazil, 30622-020
Contact: André Belisário, PhD       andrebelisario@yahoo.com.br   
HEMOPE - Pernambuco Not yet recruiting
Recife, Pernambuco, Brazil, 52011-000
Contact: Paulo Loureiro, MD, PhD       paula.loureiro10@gmail.com   
Contact: Dahra Teles, MD       dahra.teles@gmail.com   
HEMORIO - Rio De Janeiro Not yet recruiting
Rio De Janeiro, Brazil, 20211-030
Contact: Luiz Amorim, MD, PhD       luizamorimfilho@gmail.com   
Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Not yet recruiting
São Paulo, Brazil, 05403-000
Contact: Carla Dinardo, MD, PhD       caludinardo@gmail.com   
Contact: Miriam Park, MD, PhD       parkmiriam0@gmail.com   
Sponsors and Collaborators
Westat
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Eldad A Hod, MD Columbia University
Principal Investigator: Brian Custer, PhD, MPH Vitalant Research Institute
Additional Information:
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Responsible Party: Westat
ClinicalTrials.gov Identifier: NCT05255445    
Other Study ID Numbers: 75N92019D00032
75N92019D00033 ( Other Grant/Funding Number: National Heart, Lung and Blood Institute )
75N92019D00034 ( Other Grant/Funding Number: National Heart, Lung and Blood Institute )
75N92019D00035 ( Other Grant/Funding Number: National Heart, Lung and Blood Institute )
75N92019D00036 ( Other Grant/Funding Number: National Heart, Lung and Blood Institute )
75N92019D00037 ( Other Grant/Funding Number: National Heart, Lung and Blood Institute )
75N92019D00038 ( Other Grant/Funding Number: National Heart, Lung and Blood Institute )
First Posted: February 24, 2022    Key Record Dates
Last Update Posted: March 21, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified public use datasets will be created and delivered to NHLBI at the end of the study (and end of the REDS-IV-P program) and will be made available indefinitely for future analysis
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: At the end of the REDS-IV-P program, estimated in March 2026, the public use data sets will be available and will be available indefinitely for future analytic use.
Access Criteria: Public use datasets will be posted to NIH/NHLBI data repository systems.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Westat:
Transfusion
Red Blood Cell
Sickle Cell Disease
Thalassemia
Pediatric
Oncology
RBC survival
Genetic
Non-genetic
Observational
Blood donor
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn