Sickle Cells DiseasePhase 1/2RBCNCT04156893
RH Genotype Matched RBC Transfusions
A Phase 1/2 study testing Red cell units that are genotype matched at the RHD and RHCE loci in people with Sickle Cells Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
To determine the feasibility and efficacy of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Sickle Cells Disease
- What is being tested?
- Red cell units that are genotype matched at the RHD and RHCE loci
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jan 2020to Oct 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects age >6 months
- Diagnosis of SCD, all genotypes
- Require a period of chronic red cell transfusion therapy
- Subject/parental/guardian permission (informed consent) and if appropriate, child assent
Who cannot join
- 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
- Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Stella Chou, MD, 215-590-0947, chous@chop.edu
Stella Chou, MD
About this study
Official title: RH Genotype Matched Red Cell Transfusions for Patients With Sickle Cell Disease
To determine the feasibility and efficacy of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD.
Read the detailed description
This is a Phase 1/2 trial 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 three years, whichever is shorter. In the pilot phase, we have determined it is feasible to identify RH matched donor units for the patient's RH genotype for every scheduled transfusion. We will now continue to show feasibility as well as determine efficacy by monitoring Rh alloantibody formation.
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.
- Conditions
- Sickle Cells Disease
- Being tested
- Red cell units that are genotype matched at the RHD and RHCE loci
- Keywords
- Chronic Transfusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Red cell units that are genotype matched at the RHD and RHCE lociBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| RH genotype matched red cell transfusions | Experimental | 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. Receives: Biological: Red cell units that are genotype matched at the RHD and RHCE loci |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the treatment efficacy by monitoring the rate of Rh alloimmunization
A primary objective is to determine whether providing RH genotype matched red cell units can reduce or prevent Rh alloimmunization.
Measured: 3.5 years
Determine the feasibility of identifying sufficient RH genotype matched units
A primary objective is to determine the feasibility of identifying sufficient RH genotype matched red cells for chronically transfused patients with SCD with varied RH genotypes. 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.
Measured: 3.5 years
Secondary outcomes (1)
Determine the rate of non-Rh alloimmunization
A secondary objective is to determine the rate of antibody formation outside the Rh blood group system, such as anti-Kidd or -S/s.
Measured: 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study start30 Jan 2020
- Primary completionApr 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Sickle Cells DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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 days
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- New York Blood Center, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Stella Chou, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04156893
- Sponsor's protocol ID
- 19-016565
- Other IDs
- R01HL147879, R01HL169401
- Acronym
- RBC
- Status last verified
- Apr 2026
- First submitted
- 6 Nov 2019
- Last updated
- 27 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Protected Health Information (PHI) will be shared with the New York Blood Center (NYBC) to order blood for the subjects. This will be done using a secure online blood ordering system. The NYBC uses an FDA-approved HIPAA secure system called Blood Enterprise Computer System (BECS) to store patient data and results, including PHI. 3rd party computers at New York Blood Center will also store study data using study identification (ID) numbers. The purpose of having study data coded at NYBC is for specialized testing for red antigens or antibodies for which we will provide some clinical data to assist in the laboratory evaluation. To assure that the transmission of data and samples maintains confidentiality we will used study ID numbers for these samples. The master list will be maintained at the Children's Hospital of Philadelphia (CHOP). The study databases are password protected and on password protected computers at CHOP and at NYBC, that are backed up on the research servers.
Publications
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.
PubMed 23723452Vichinsky 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. doi: 10.1056/NEJM199006073222301.
PubMed 2342522Yawn 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.
PubMed 25203083Chou 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.
PubMed 30026182Coleman 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.
PubMed 31021439Mewha J, Vege S, Friedman DF, Makrm S, Ochoa G, Westhoff CM, Chou ST. Red cell antigen exposures in patients with sickle cell disease receiving transfusion from Black and Hispanic donors. Blood Red Cells Iron. 2026 Jun;2(2):100059. doi: 10.1016/j.brci.2026.100059. Epub 2026 Apr 8.
PubMed 42376265
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RH Genotype Matched Red Cell Transfusions for Patients With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT04156893
- Acronym / sponsor ID
- RBC / 19-016565
- Conditions
- Sickle Cells Disease
- Keywords
- Chronic Transfusion
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- New York Blood Center, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 30 Jan 2020 (actual)
- Primary completion
- Apr 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 8 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the feasibility and efficacy of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD.
Detailed description
This is a Phase 1/2 trial 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 three years, whichever is shorter. In the pilot phase, we have determined it is feasible to identify RH matched donor units for the patient's RH genotype for every scheduled transfusion. We will now continue to show feasibility as well as determine efficacy by monitoring Rh alloantibody formation.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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 days
| Arm | Type | Receives |
|---|---|---|
| RH genotype matched red cell transfusions | Experimental | Biological: Red cell units that are genotype matched at the RHD and RHCE lociSubjects 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. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects age >6 months
- Diagnosis of SCD, all genotypes
- Require a period of chronic red cell transfusion therapy
- Subject/parental/guardian permission (informed consent) and if appropriate, child assent
Key exclusion criteria (5 listed)
- 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
- Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Red cell units that are genotype matched at the RHD and RHCE lociPatients 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. | Biological | RH genotype matched red cell transfusions |
Primary outcome
Determine the treatment efficacy by monitoring the rate of Rh alloimmunization
Time frame: 3.5 years
A primary objective is to determine whether providing RH genotype matched red cell units can reduce or prevent Rh alloimmunization.
Determine the feasibility of identifying sufficient RH genotype matched units
Time frame: 3.5 years
A primary objective is to determine the feasibility of identifying sufficient RH genotype matched red cells for chronically transfused patients with SCD with varied RH genotypes. 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.
1 secondary outcome
Determine the rate of non-Rh alloimmunization
Time frame: 3.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
- Background: PubMed 23723452Chou 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.
- Background: PubMed 2342522Vichinsky 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. doi: 10.1056/NEJM199006073222301.
- Background: PubMed 25203083Yawn 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.
- Background: PubMed 30026182Chou 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.
- Background: PubMed 31021439Coleman 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.
- Derived from this study: PubMed 42376265Mewha J, Vege S, Friedman DF, Makrm S, Ochoa G, Westhoff CM, Chou ST. Red cell antigen exposures in patients with sickle cell disease receiving transfusion from Black and Hispanic donors. Blood Red Cells Iron. 2026 Jun;2(2):100059. doi: 10.1016/j.brci.2026.100059. Epub 2026 Apr 8.
- Individual participant dataSharing planned: Yes. Protected Health Information (PHI) will be shared with the New York Blood Center (NYBC) to order blood for the subjects. This will be done using a secure online blood ordering system. The NYBC uses an FDA-approved HIPAA secure system called Blood Enterprise Computer System (BECS) to store patient data and results, including PHI. 3rd party computers at New York Blood Center will also store study data using study identification (ID) numbers. The purpose of having study data coded at NYBC is for specialized testing for red antigens or antibodies for which we will provide some clinical data to assist in the laboratory evaluation. To assure that the transmission of data and samples maintains confidentiality we will used study ID numbers for these samples. The master list will be maintained at the Children's Hospital of Philadelphia (CHOP). The study databases are password protected and on password protected computers at CHOP and at NYBC, that are backed up on the research servers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Stella Chou, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Red cell units that are genotype matched at the RHD and RHCE loci in people with Sickle Cells Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stella Chou, MD (215-590-0947, chous@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the treatment efficacy by monitoring the rate of Rh alloimmunization (time frame: 3.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04156893, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026; AzTrials last refreshed its copy on 30 Oct 2026.