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

Sponsor

Westat (Other)

Overall Status

Recruiting

CT.gov ID

NCT05255445

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

500

Enrollment

Locations

35.5

Anticipated Duration (Months)

35.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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	Phase
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.

Study Design

Study Type:

Observational

Anticipated 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 :

Mar 16, 2022

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	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.

Outcome Measures

Primary Outcome Measures

Change in Hemoglobin A or Hemoglobin Level per day (RBC Survival) [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
Change in Serum Iron Level [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

Hemoglobin Increment [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"
Hemolysis Parameter Increment [Baseline (immediately pre-) to post-transfusion or 2-hours post-transfusion, over 2 years]
Includes serum iron, indirect bilirubin, or plasma free hemoglobin
Hepcidin Level [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
Non-Transferrin-Bound Iron (NTBI) Level [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
Number of Clinical Complications [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

Rate of Alloimmunization [2 years]
Rate of new alloantibody formation
4-hydroxynonenal [4-HNE] [2 years]
Recipient oxidative stress pre-transfusion is associated with "RBC survival"
Type I interferon (i.e., MxA protein assay) and other cytokines (i.e., IL-6, MCP-1, IFNgamma) [2 years]
Recipient inflammation pre-transfusion is associated with "RBC survival"
Number of Transfusion Reactions [2 years]
Transfusion reactions are associated with "RBC survival"

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Benioff Children's Hospital	Oakland	California	United States	94609
2	Vitalant Research Institute	San Francisco	California	United States	94118
3	Boston Children's Hospital	Boston	Massachusetts	United States	02115
4	Weill Cornell Medical Collection (WCMC)/New York Presbyterian Hospital (NYPH)	New York	New York	United States	10021
5	Columbia University Irving Medical Center/New York Presbyterian Hospital (NYPH)	New York	New York	United States	10032
6	New York Blood Center (NYBC)	New York	New York	United States	10065
7	Children's Wisconsin	Milwaukee	Wisconsin	United States	53226
8	Froedtert Hospital	Milwaukee	Wisconsin	United States	53226
9	Versiti Wisconsin, Inc.	Milwaukee	Wisconsin	United States	53233
10	HEMOAM - Amazonas	Manaus	Amazonas	Brazil	69050-001
11	HEMOMINAS - Minas Gerais	Belo Horizonte	Minas Gerais	Brazil	30622-020
12	HEMOPE - Pernambuco	Recife	Pernambuco	Brazil	52011-000
13	HEMORIO - Rio De Janeiro	Rio De Janeiro		Brazil	20211-030
14	Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo		Brazil	05403-000