Red Blood Cell - IMProving trAnsfusions for Chronically Transfused Recipients

Sickle Cell Disease Clinical Trial

— RBC-IMPACT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05255445
• Other study ID #: 75N92019D00032
• Secondary ID: 75N92019D0003375
• Status: Completed
• Start date: March 16, 2022
• Est. completion date: March 31, 2024

Study information

• Verified date: May 2024
• Source: Westat
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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 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)

Exclusion Criteria (Aim #1):

• Institutionalization or imprisonment

• Foster care

• Weight <11 kg

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

• Weight <18 kg

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Pediatric Cancer
• Sickle Cell Disease
• Thalassemia

Intervention

Biological:
• Red Blood Cell (RBC) Transfusion
Simple RBC transfusion or partial manual exchange

Locations

Country	Name	City	State
Brazil	HEMOMINAS - Minas Gerais	Belo Horizonte	Minas Gerais
Brazil	HEMOAM - Amazonas	Manaus	Amazonas
Brazil	HEMOPE - Pernambuco	Recife	Pernambuco
Brazil	HEMORIO - Rio De Janeiro	Rio De Janeiro
Brazil	Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Children's Wisconsin	Milwaukee	Wisconsin
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	Versiti Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Columbia University Irving Medical Center/New York Presbyterian Hospital (NYPH)	New York	New York
United States	New York Blood Center (NYBC)	New York	New York
United States	Weill Cornell Medical Collection (WCMC)/New York Presbyterian Hospital (NYPH)	New York	New York
United States	UCSF Benioff Children's Hospital	Oakland	California
United States	Vitalant Research Institute	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Westat	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of Alloimmunization	Rate of new alloantibody formation	2 years
Other	4-hydroxynonenal [4-HNE]	Recipient oxidative stress pre-transfusion is associated with "RBC survival"	2 years
Other	Type I interferon (i.e., MxA protein assay) and other cytokines (i.e., IL-6, MCP-1, IFNgamma)	Recipient inflammation pre-transfusion is associated with "RBC survival"	2 years
Other	Number of Transfusion Reactions	Transfusion reactions are associated with "RBC survival"	2 years
Primary	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
Primary	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	Hemoglobin Increment	Hemoglobin increment [defined as Hb/HbA(post-transfusion)visit(i) - Hb/HbA(pre-transfusion)visit(i)] is associated with "RBC survival"	Baseline (immediately pre-) to post-transfusion, over 2 years
Secondary	Hemolysis Parameter Increment	Includes serum iron, indirect bilirubin, or plasma free hemoglobin	Baseline (immediately pre-) to post-transfusion or 2-hours post-transfusion, over 2 years
Secondary	Hepcidin Level	Hepcidin level at time of transfusion is a predictor of change in iron parameters (i.e., transferrin saturation, serum iron) following transfusion	Baseline (immediately before) to 2 hours after transfusion
Secondary	Non-Transferrin-Bound Iron (NTBI) Level	NTBI levels in patients with pediatric oncologic diagnoses with aplasia are elevated at baseline and increase following transfusion	Baseline (immediately before) to 2 hours after transfusion
Secondary	Number of Clinical Complications	Increased NTBI, serum iron, or transferrin saturation following transfusion is associated with increased risk of clinical adverse effects (i.e., new infections, SCD complications)	2 years

External Links

•   REDS-IV-P public website