Prophylactic Transfusion In Pregnant in Women With Sickle Cell Disease (ProTIP)

Emory University

Status and phase: Not yet enrolling; Phase 4

Conditions: Pregnancy Related; Sickle Cell Disease

Treatments: Biological: Prophylactic Transfusion Intervention group: Transfusion; Other: Control group

Study type: Interventional

Funder types: Other

Identifiers

NCT06979492

STUDY00007288

Details and patient eligibility

About

The goal of this study is to determine if there is a positive effect of prophylactic red blood cell (RBC) transfusion of leukoreduced, ABO, Rh (D/Cc/Ee) and Kell matched blood compared to standard of care on the number of episodes of acute sickle cell disease (SCD) manifestations or pregnancy-related complications requiring acute health care encounters (acute care/ER/Hospital visits) or resulting in death over the entirety of pregnancy until 2 months post-partum in women with SCD.

RBC transfusion is the only disease-modifying therapy for pregnant women with SCD, and it is considered a standard treatment option however, there exists no consensus on the role of transfusion therapy in preventing SCD-related pregnancy complications.

Participants will be randomly assigned to repeated red blood cell transfusions or the standard of care. Participants will be on study for about 8-10 months (Pregnancy through 2 months post-partum).

Full description

Sickle cell disease (SCD) is a common genetic disorder that results from the homozygous presence of abnormal β-globin chains (hemoglobin Hb SS, Hb SC, HbSβ thalassemia). SCD causes red blood cells to become rigid, leading to various acute and chronic manifestations: chronic hemolytic anemia, poor growth, acute vaso-occlusive pain crises (VOC), priapism (in men) acute ischemic stroke, acute chest syndrome (ACS), and chronic organ damage within the spleen, kidneys, liver, lungs and heart.

High rates of both maternal and fetal morbidity and mortality complicate pregnancy in patients affected by SCD. SCD pregnancies have been linked to higher rates of obstetrical complications, including preeclampsia, venous thromboembolism, intrauterine growth restriction, preterm delivery, and small-for-gestational-age infants. In addition, sickle-related maternal complications are common during pregnancy. More than 50% of women with SCD have a VOC in the antenatal period (76% for HbSS vs 27% for Hb SC). ACS in pregnancy is seen in 7% to 20% of women with HbSS and approximately 5% in women with HbSC. Prophylactic transfusion therapy has established benefits in stroke prevention and preoperative optimization in SCD patients, but its use in pregnancy has not been established. Because hydroxyurea (HU) may be teratogenic, RBC transfusion is the only disease-modifying therapy available for pregnant women with SCD.

The decision to put a pregnant woman with SCD on chronic transfusion therapy is entirely based on provider preference and patient willingness. RBC transfusions are considered a standard treatment option for pregnant women with SCD and transfusion therapy widely used, however there exists no consensus among providers on the role of chronic transfusion therapy in preventing SCD-related pregnancy complications and no prospective randomized controlled study investigating the role of prophylactic transfusion for prevention of both maternal and fetal morbidity has been done.

Enrollment: 50 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Female
• Diagnosis of SCD of any genotype (i.e., HbSS, HbSC, HbSβ thalassemia)
• 18 Years and older
• Currently pregnant at 6 weeks through 20 weeks of gestation.
• Ability to understand the purposes and risks of the study and willingly give informed consent.
• For participants with private health insurance, insurance pre-approval for blood transfusions

Exclusion criteria

• Currently on chronic transfusion therapy before pregnancy
• Prior history of DHTR with hyperhemolysis
• Red cell antibody history, which would prevent the provision of adequate red cell units to support chronic transfusions.
• Unable or unwilling to receive blood transfusion for social, religious, or clinical reasons
• Known current triplet pregnancy
• Current diagnosis of major medical or psychiatric comorbidity, which in the randomizing clinician's opinion renders them unable to enter a clinical trial.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Standard of Care

Other group

Description:

Patients randomized to the control group will receive standard care for SCD alone. As part of the standard of care, women with SCD who become pregnant and who are on hydroxyurea (HU) will have the HU suspended by their primary SCD provider.

Treatment:

Other: Control group

Red Blood Cell (RBC) Transfusion

Experimental group

Description:

Participants will receive a blood transfusion between 6 and 20 weeks of gestation. It will be repeated at 3-6 week intervals, aiming to maintain HbS \<30%

Treatment:

Biological: Prophylactic Transfusion Intervention group: Transfusion