RH Genotype Matched RBC Transfusions

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04156893
• Collaborator: New York Blood Center (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 35
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 53
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

To determine the feasibility of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cells Disease	Biological: Red cell units that are genotype matched at the RHD and RHCE loci	Early Phase 1

Detailed Description

This is a pilot feasibility study in patients with Sickle Cell Disease requiring chronic red cell transfusions. RH genotyped donor units will be obtained from the New York Blood Center. Patients will be matched with donor units whose RH genotypes predict no foreign Rh protein exposure to the patient. This will provide red cell matching at a level above the current standard of care (serologic C, E, and K matching). Patients will receive RH matched red cells for the duration of their chronic transfusion therapy or up to five years, whichever is shorter. It will then be determined whether sufficient RH matched donor units can be identified for the patient's RH genotype. Although not powered to determine effectiveness, all patients's Rh alloantibody formation will be monitored.

For subjects with a history of stroke/recurrent transient ischemic attack or other indication who require tight control of Hb S, and RH genotyped blood is not available, standard of care serologic matched blood would be administered rather than delaying transfusion and risking higher Hb S level.

For all subjects, standard of care serologic matched blood would be administered rather than delaying transfusion beyond 7 days.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Subjects will receive RH genotype matched red cell units for transfusion. For subjects with a history of stroke/recurrent transient ischemic attack or other indication who require tight control of Hb S, and RH genotyped blood is not available, standard of care serologic matched blood would be administered rather than delaying transfusion and risking higher Hb S level. For all subjects, standard of care serologic matched blood would be administered rather than delaying transfusion beyond 7 daysSubjects will receive RH genotype matched red cell units for transfusion. For subjects with a history of stroke/recurrent transient ischemic attack or other indication who require tight control of Hb S, and RH genotyped blood is not available, standard of care serologic matched blood would be administered rather than delaying transfusion and risking higher Hb S level. For all subjects, standard of care serologic matched blood would be administered rather than delaying transfusion beyond 7 days
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: RH Genotype Matched Red Cell Transfusions for Patients With Sickle Cell Disease
• Actual Study Start Date: Jan 30, 2020
• Anticipated Primary Completion Date: Jul 1, 2023
• Anticipated Study Completion Date: Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RH genotype matched red cell transfusions Subjects will receive RH genotyped matched red cell units for transfusion in addition to standard serologic C, E, and K antigen matching and being hemoglobin S negative, which is our institutional standard of care for patients with Sickle Cell Disease.	Biological: Red cell units that are genotype matched at the RHD and RHCE loci; Patients will be provided with red cell units that are C, E, and K antigen matched (standard of care for patients with SCD) and genotype matched at the RHD and RHCE loci.

Outcome Measures

Primary Outcome Measures

1. Feasibility of identifying sufficient RH genotype matched units [5.5 years]

   The primary objective of this study is to determine the feasibility of RH genotype matched red cells for chronically transfused patients with SCD. Approximately 20 RHD (Rhesus D) and 20 RHCE (Rhesus CE) variants have been observed in patients with SCD, and will determine whether sufficient RH genotyped units can be matched to the patient's own RH genotype.

Secondary Outcome Measures

1. Determine the occurrence of Rh alloimmunization [5.5 years]

   The secondary objective is to determine if there is a relationship between providing RH genotype matched red cell units to Rh alloimmunization. Although not powered to determine effectiveness, our secondary objective is to monitor for Rh alloimmunization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects age >12 months

• Diagnosis of SCD, all genotypes

• Require a period of chronic red cell transfusion therapy

Exclusion Criteria:

• Rare RH genotype that would preclude identification of sufficient RBC units

• Antigen negative requirements due to alloimmunization that would preclude identification of sufficient RBC units

• Alloimmunized to D antigen

• Rh alloimmunized patients for whom providing RH genotype matched blood would expose the patient to an antigen that would not be consistent with standard of care and blood bank protocols

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia
• New York Blood Center
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Stella Chou, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chou ST, Evans P, Vege S, Coleman SL, Friedman DF, Keller M, Westhoff CM. RH genotype matching for transfusion support in sickle cell disease. Blood. 2018 Sep 13;132(11):1198-1207. doi: 10.1182/blood-2018-05-851360. Epub 2018 Jul 19.
• Chou ST, Jackson T, Vege S, Smith-Whitley K, Friedman DF, Westhoff CM. High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Blood. 2013 Aug 8;122(6):1062-71. doi: 10.1182/blood-2013-03-490623. Epub 2013 May 30.
• Coleman S, Westhoff CM, Friedman DF, Chou ST. Alloimmunization in patients with sickle cell disease and underrecognition of accompanying delayed hemolytic transfusion reactions. Transfusion. 2019 Jul;59(7):2282-2291. doi: 10.1111/trf.15328. Epub 2019 Apr 25.
• Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med. 1990 Jun 7;322(23):1617-21.
• Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517. Review. Erratum in: JAMA. 2014 Nov 12;312(18):1932. JAMA. 2015 Feb 17;313(7):729.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT04156893
• Other Study ID Numbers: 19-016565; R01HL147879-01
• First Posted: Nov 8, 2019
• Last Update Posted: Aug 11, 2022
• Last Verified: Aug 1, 2022

• 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 Children's Hospital of Philadelphia: Chronic Transfusion
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

No Results Posted as of Aug 11, 2022