Red Blood Cell Exchange for Sickle Cell Disease

(SCD-CARRE Trial)

Not currently recruiting at 27 trial locations

Overseen By Nydia Chien, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Pittsburgh

Disqualifiers: RBC alloimmunization, Hyper-hemolysis, Severe transfusion reaction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether automated exchange blood transfusion can aid adults with sickle cell disease (SCD) who face a high risk of serious health issues. The aim is to determine if this treatment reduces emergency visits or hospital stays due to SCD complications over a year. Participants will receive either the standard treatment for SCD or the standard treatment plus these blood transfusions every 3-6 weeks. Suitable candidates have sickle cell disease and are not currently on a regular exchange transfusion program. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop taking my current medications for the trial?

If you are on a sickle cell disease drug like hydroxyurea, glutamine, or P-selectin inhibitors, your doses must be stable for at least 60 days before joining the trial. You must stop taking Oxbryta at least 30 days before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that automated exchange blood transfusion is generally safe for people with sickle cell disease. Studies indicate that this treatment can be used safely and effectively, even for those at high risk of stroke. It also improves patients' quality of life. This method is often preferred over simple transfusions because it uses fewer red blood cells. Overall, automated exchange blood transfusion is considered a valuable and well-tolerated option for managing sickle cell disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Researchers are excited about automated exchange blood transfusion for sickle cell disease because it offers a unique approach compared to standard treatments. Unlike regular blood transfusions, which can lead to iron overload, this method efficiently swaps out sickled cells for healthy ones without accumulating excess iron. This technique is administered every 3–6 weeks and could provide more consistent management of the disease's symptoms over a 12-month period. By potentially reducing complications and improving quality of life, this method represents a promising advancement in sickle cell care.

What evidence suggests that automated exchange blood transfusion might be an effective treatment for sickle cell disease?

Studies have shown that automated exchange blood transfusion can greatly benefit people with sickle cell disease. This process replaces sickle-shaped red blood cells with healthy ones, reducing the risk of complications. Research indicates that this method can decrease iron buildup in the body, a common issue with regular blood transfusions. In this trial, some participants will receive automated exchange blood transfusion alongside standard care. Patients and doctors have reported improved quality of life with this treatment. Overall, automated exchange transfusions appear to be a safe and effective way to manage sickle cell disease. ^{2 3 6 7 8}

Who Is on the Research Team?

Maria Brooks, PhD

Principal Investigator

University of Pittsburgh

Mark Gladwin, MD

Principal Investigator

University of Maryland

Darrell Triulzi, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

Adults over 18 with Sickle Cell Disease at high risk of health complications, not on chronic blood exchange for 60 days, stable medication doses if taking SCD drugs. Excludes those with a history of severe transfusion reactions or conditions like liver failure that increase trial risks.

Inclusion Criteria

Written informed consent obtained from patient to participate in the trial.

I haven't been on a regular blood exchange program for the last 60 days.

My eligibility biomarkers were tested in a stable condition, not during an acute pain event.

Exclusion Criteria

I've had a severe reaction to a blood transfusion causing kidney failure or serious issues like low blood pressure or breathing problems.

I've been hospitalized over 10 times in the last year for pain crises.

You have had a condition called hyper-hemolysis syndrome in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard of care or automated exchange blood transfusion every 3-6 weeks for 12 months

12 months

Monthly visits for transfusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Long-term monitoring

Participants are assessed for survival and acute healthcare encounters over 13 months

13 months

What Are the Treatments Tested in This Trial?

Interventions

• Automated Exchange Blood Transfusion
• Standard of Care

Trial Overview The SCD-CARRE study is testing whether automated red blood cell exchanges plus standard care can reduce health emergencies or death in high-risk adult sickle cell patients compared to standard care alone over a year.

How Is the Trial Designed?

Group I: Exchange transfusion plus standard of care Experimental Treatment 2 Interventions

Randomized to standard of care and automated exchange blood transfusion every 3-6 weeks for 12 months.

Group II: Standard of care Active Control 1 Intervention

Randomized to standard of care

Automated Exchange Blood Transfusion is already approved in United States, European Union for the following indications:

Approved in United States as Red Cell Exchange for:

• Acute chest syndrome
• Stroke
• Multi-organ failure syndromes
• Right upper quadrant syndrome
• Priapism
• Chronic management of sickle cell disease

Approved in European Union as Red Cell Exchange for:

• Acute chest syndrome
• Stroke
• Multi-organ failure syndromes
• Right upper quadrant syndrome
• Priapism
• Chronic management of sickle cell disease

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Mark Gladwin

Lead Sponsor

Trials

3

Recruited

340+

Gladwin, Mark, MD

Lead Sponsor

Trials

15

Recruited

430+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Manual exchange transfusion (MET) is as effective as automated exchange transfusion (AET) in reducing hemoglobin S levels and preventing strokes in children with sickle cell anemia, based on a study of 39 children and 1353 exchange sessions.

Both methods are safe and well-tolerated, but MET is significantly more cost-effective, with equipment costs being 74 times lower than AET, making it feasible for use in all hospital settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of automated erythrocytapheresis versus manual exchange transfusion to treat cerebral macrovasculopathy in sickle cell anemia. Koehl, B., Sommet, J., Holvoet, L., et al.[2018]

In a study of 38 pediatric patients with sickle cell disease undergoing 760 chronic automated red cell exchange procedures, 19.7% experienced adverse events (AEs), with hypocalcemia being the most common at 15.4%.

Patients with a baseline hematocrit (Hct) of 30% or higher, low systolic blood pressure, severe CNS vasculopathy, and non-sickle cell anemia genotypes were found to be at higher risk for these AEs, suggesting the need for individualized risk assessments before procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Procedural adverse events in pediatric patients with sickle cell disease undergoing chronic automated red cell exchange. Wade, J., Yee, MEM., Easley, KA., et al.[2022]

In a study of 20 sickle cell patients over an average of 6 years, manual or automatic red blood cell exchanges were found to be safe, with no complications related to the procedure or increased blood use.

Automatic red blood cell exchanges not only effectively prevented complications of sickle cell disease but also reduced iron overload and ferritin levels, while using Single Donor Red Blood Cell units minimized the risk of transfusion-transmitted infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic red blood cell exchange to prevent clinical complications in sickle cell disease. Cabibbo, S., Fidone, C., Garozzo, G., et al.[2014]

In a study of 86 episodes of red blood cell exchange for acute sickle cell complications, both automated and manual methods were effective, with post-procedure Hb S levels significantly lower after automated exchange (18%) compared to manual exchange (36%).

Manual red cell exchange proved to be a safe and effective alternative to automated procedures, with similar clinical outcomes in terms of organ support needs and hospital stay duration, making it a viable option while facilities expand their automated capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergency red cell exchange for the management of acute complications in sickle cell disease: Automated versus manual. Mihalca, D., Ahmad, A., Mehta, D., et al.[2023]

Automated red blood cell exchange is more effective than manual exchange in reducing sickle hemoglobin levels in young patients with sickle cell disease, achieving a greater decrease per volume removed.

Both procedures were safe, with no major complications reported, but automated exchange allowed for better control of volume status and avoided iron overload, making it a preferable option for managing sickle cell disease complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial Red Blood Cell Exchange in Children and Young Patients with Sickle Cell Disease: Manual Versus Automated Procedure. Escobar, C., Moniz, M., Nunes, P., et al.[2018]

Chronic erythrocytapheresis has been effectively used in 16 patients under 20 years old with sickle-cell disease, showing significant improvements in 12 patients, particularly in those receiving primary prevention for cerebrovascular disease and pain crisis recurrence.

The treatment resulted in better quality of life for patients and normalized ferritin levels in those with iron overload, while being less resource-intensive compared to traditional transfusion methods, despite some challenges with venous access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advantages and difficulties of an erythrocytapheresis program for sickle-cell patients: a pediatric experience]. Filhon, B., Dumesnil, C., Holtermann, C., et al.[2012]

Manual partial red cell exchange (RCE) was successfully performed on 44 sickle cell patients, showing complete symptom regression in 100% of cases with persistent vaso-occlusive crises and acute chest syndrome, indicating its high efficacy in severe complications of sickle cell disease.

The procedure was found to be safe, with no cases of alloimmunization or viral infections reported, demonstrating that RCE can be effectively and safely implemented even in low-resource settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Manual Partial Red Cell Exchange in the Management of Severe Complications of Sickle Cell Disease in a Developing Country. Faye, BF., Sow, D., Seck, M., et al.[2020]

Automated red blood cell exchange (aRBCX) was found to be more effective than manual exchange transfusion (MET) in reducing the percentage of sickle hemoglobin (HbS) in adult patients with sickle cell disease, leading to better disease control and fewer hospital visits.

Despite requiring more packed red blood cells (pRBCs) for aRBCX, patients experienced significantly lower ferritin levels, indicating better iron management and a reduced risk of complications associated with chronic transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study between chronic automated red blood cell exchange and manual exchange transfusion in patients with sickle cell disease: A single center experience from Saudi Arabia. Al Mozain, N., Elobied, Y., Al-Omran, A., et al.[2023]

Automated erythrocytapheresis using the IBM 2997 Blood Cell Separator effectively managed symptoms in two patients with sickle cell disease, demonstrating its potential as a therapeutic intervention.

In one case, the procedure not only prevented complications during surgery but also alleviated acute sickle crisis symptoms and resolved respiratory issues, highlighting its efficacy in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythrocytapheresis (red cell exchange). Sentinella, K., Thompson, R., Hunt, D., et al.[2004]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12559512/

The Economic and Clinical Impact of Recurring Automated ... Logistics, risks, and benefits of automated red blood cell exchange for patients with sickle cell disease. Hematology. 2023;2023(1):646–52 ...

2. ashpublications.org ashpublications.org/hematology/article/2023/1/646/506394/Logistics-risks-and-benefits-of-automated-red

Logistics, risks, and benefits of automated red blood cell ... Automated exchange compared to manual and simple blood transfusion attenuates rise in ferritin level after 1 year of regular blood transfusion ...

3. terumobct.com terumobct.com/en/gl/our-company/news-and-events/news-releases/2024/patients--scientists-agree--automated-red-blood-cell-exchange-en.html

Automated Red Blood Cell Exchange Enhances Quality of ... Patients, Scientists Agree: Automated Red Blood Cell Exchange Enhances Quality of Life in Sickle Cell Disease Patients. Recent peer-reviewed study supports ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10905321/

Logistics, risks, and benefits of automated red blood cell ... Automated RBC exchange is therefore an isovolemic transfusion that can efficiently decrease HbS RBCs while limiting iron loading and hyperviscosity.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473050223000939

The implementation of automated red blood cell exchange ... Conclusion. Automated RBCX is safe and effective modality for management of patients with sickle cell disease. Financial support. The authors ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33368343/

Safety and benefits of automated red cell depletion ... Our study supports that IHD-RCE can be safely used in patients with stroke risk and compared to standard RCE, results in benefits of lower RBC usage.

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/vox.13288

Comparative evaluation of efficacy and safety of automated ... Exchange transfusion is a valuable treatment option in sickle cell disease (SCD) and is preferred over simple transfusion as it removes ...

8. healthcare-bulletin.co.uk healthcare-bulletin.co.uk/article/study-of-automated-red-cell-exchange-in-the-management-of-sickle-cell-disease-in-a-tertiary-care-hospital-of-indore-district-2778/

Study Of Automated Red Cell Exchange in The ... In conclusion, automated red cell exchange (A-RCE) appears to be a safe and effective treatment for patients with sickle cell disease. Our ...