Red Blood Cell Exchange for Sickle Cell Disease

(SCD-CARRE Trial)

Recruiting at 24 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

173 Participants Needed

Trial Summary

What is the purpose of this trial?

The SCD-CARRE trial is a Phase 3, prospective, randomized, multicenter, controlled, parallel two-arm study aimed to determine if automated exchange blood transfusion and standard of care administered to high mortality risk adult SCD patients reduces the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/hospital visits) or resulting in death over 12 months as compared with standard of care.

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.

What data supports the effectiveness of the treatment Automated Exchange Blood Transfusion for Sickle Cell Disease?

Research shows that automated red blood cell exchange can effectively manage acute complications in sickle cell disease by improving anemia and oxygen delivery while reducing sickle cells in the blood. It has been successful in preventing strokes and improving quality of life in patients, although it requires specialized resources and can have challenges like venous access issues. ^{1 2 3 4 5}

Is red blood cell exchange safe for humans?

Research shows that red blood cell exchange, whether done manually or automatically, is generally safe for people with sickle cell disease. Studies have found no complications related to the procedure over several years, and it can even reduce the risk of infections from blood transfusions. ^{2 6 7 8 9}

How is automated red blood cell exchange different from other treatments for sickle cell disease?

Automated red blood cell exchange is unique because it quickly reduces the number of sickle-shaped red blood cells and improves oxygen delivery to tissues, which can help manage acute complications of sickle cell disease. Unlike manual methods, it is more efficient and requires less time, but it may not be available 24/7 in all centers. ^{1 2 3 4 5}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Erythrocytapheresis (red cell exchange). [2004]

2. Portugal pubmed.ncbi.nlm.nih.gov

Partial Red Blood Cell Exchange in Children and Young Patients with Sickle Cell Disease: Manual Versus Automated Procedure. [2018]

3. France pubmed.ncbi.nlm.nih.gov

[Advantages and difficulties of an erythrocytapheresis program for sickle-cell patients: a pediatric experience]. [2012]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of automated erythrocytapheresis versus manual exchange transfusion to treat cerebral macrovasculopathy in sickle cell anemia. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Emergency red cell exchange for the management of acute complications in sickle cell disease: Automated versus manual. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Procedural adverse events in pediatric patients with sickle cell disease undergoing chronic automated red cell exchange. [2022]

7. United States 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. [2020]

8. India 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Chronic red blood cell exchange to prevent clinical complications in sickle cell disease. [2014]