Red Blood Cell - IMProving trAnsfusions for Chronically Transfused Recipients

NCT05255445 | Completed DMC FDA Drug

• 7 other identifiers: 75N92019D0003275N92019D0003375N92019D0003475N92019D0003575N92019D0003675N92019D0003775N92019D00038
• Study Type: observational
• Target: 157
• Locations: 2 countries
• Sites: 14

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.

Conditions

Sickle Cell Disease; Thalassemia; Pediatric Cancer

Keywords

Transfusion; Red Blood Cell; Sickle Cell Disease; Thalassemia; Pediatric; Oncology; RBC survival; Genetic; Non-genetic; Observational; Blood donor

Outcome Measures

Primary Outcomes (2)

• Change in Hemoglobin A or Hemoglobin Level per day (RBC Survival)

  Change in hemoglobin A or hemoglobin level per day in between subsequent transfusion episodes, for sickle cell disease and thalassemia cohorts, respectively

  Baseline (immediately pre-) to post-transfusion over 2 years

• Change in Serum Iron Level

  For all groups participating, change in serum iron measured from immediately prior to 2 hours post-transfusion

  Baseline (immediately before) and 2-hours after transfusion

Secondary Outcomes (5)

• Hemoglobin Increment

  Baseline (immediately pre-) to post-transfusion, over 2 years

• Hemolysis Parameter Increment

  Baseline (immediately pre-) to post-transfusion or 2-hours post-transfusion, over 2 years

• Hepcidin Level

  Baseline (immediately before) to 2 hours after transfusion

• Non-Transferrin-Bound Iron (NTBI) Level

  Baseline (immediately before) to 2 hours after transfusion

• Number of Clinical Complications

  2 years

Other Outcomes (4)

• Rate of Alloimmunization

  2 years

• 4-hydroxynonenal [4-HNE]

  2 years

• Type I interferon (i.e., MxA protein assay) and other cytokines (i.e., IL-6, MCP-1, IFNgamma)

  2 years

Study Arms (4)

Sickle cell disease (SCD)

Patients with SCD who are chronically transfused (in the U.S. and Brazil)

Biological: Red Blood Cell (RBC) Transfusion

Thalassemia

Patients with thalassemia who are chronically transfused in the U.S.

Biological: Red Blood Cell (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

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.

Interventions

Red Blood Cell (RBC) Transfusion BIOLOGICAL

Simple RBC transfusion or partial manual exchange

Pediatric Hematology-Oncology; Sickle cell disease (SCD); Thalassemia

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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 (or partial manual exchange 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).

You may qualify if:

• Well-characterized transfusion-dependent form of SCD or thalassemia (including Hemoglobin E-thalassemia and sickle-beta thalassemia) on chronic simple transfusion therapy or partial manual exchange
• On a regular simple RBC transfusion schedule, including partial manual exchange (i.e., 1-3 units scheduled every 2-6 weeks and on a minimum 6-month chronic transfusion trial; for partial manual exchange, the phlebotomy must be completed before the transfusion is started without a back and forth between rounds of phlebotomy and transfusion)
• 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)

You may not qualify if:

• Institutionalization or imprisonment
• Foster care
• Weight \<11 kg
• 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).
• 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
• Weight \<18 kg

Sponsors & Collaborators

• Westat: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (14)

UCSF Benioff Children's Hospital

Oakland, California, 94609, United States

Location

Vitalant Research Institute

San Francisco, California, 94118, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Weill Cornell Medical Collection (WCMC)/New York Presbyterian Hospital (NYPH)

New York, New York, 10021, United States

Location

Columbia University Irving Medical Center/New York Presbyterian Hospital (NYPH)

New York, New York, 10032, United States

Location

New York Blood Center (NYBC)

New York, New York, 10065, United States

Location

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Versiti Wisconsin, Inc.

Milwaukee, Wisconsin, 53233, United States

Location

HEMOAM - Amazonas

Manaus, Amazonas, 69050-001, Brazil

Location

HEMOMINAS - Minas Gerais

Belo Horizonte, Minas Gerais, 30622-020, Brazil

Location

HEMOPE - Pernambuco

Recife, Pernambuco, 52011-000, Brazil

Location

HEMORIO - Rio De Janeiro

Rio de Janeiro, 20211-030, Brazil

Location

Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, 05403-000, Brazil

Location

Related Publications (1)

• Karafin MS, Kelly S, Chapman KM, Kreuziger LB, Manis JP, Dinardo C, Josephson CD, Stone M, Roubinian NH, Branchford B, Sachais BS, Hailu B, Sabino EC, Hod EA, Custer B; National Heart, Lung, and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P). The Red Blood Cell-Improving Transfusions for Chronically Transfused Recipients (RBC-IMPACT) study: protocol description of an international multi-site observational clinical study. Blood Transfus. 2025 Sep-Oct;23(5):418-432. doi: 10.2450/BloodTransfus.1026. Epub 2025 May 9.

  PMID: 40423585 DERIVED

Related Links

• REDS-IV-P public website

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).

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia; Neoplasms

Interventions

Erythrocyte Count; Blood Transfusion

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Biological Therapy; Therapeutics

Study Officials

• Eldad A Hod, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Brian Custer, PhD, MPH

  Vitalant Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2022
• First Posted: February 24, 2022
• Study Start: March 16, 2022
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

BR (5); US (9)