Prophylactic Transfusion In Pregnant in Women With Sickle Cell Disease

Обзор

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).

Подробное описание

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.

Вмешательства

• Биопрепарат Prophylactic Transfusion Intervention group: Transfusion
  For participants randomized to the prophylactic transfusion intervention group, the first RBC transfusion will occur within 3 weeks of randomization. All transfusions will be managed per SOC. SOC prophylactic RBC transfusion management is as follows: transfusions are performed at 3-6 week intervals with the intent to maintain a pre-transfusion hemoglobin S level at \<30%. All participants will have a complete blood count, reticulocyte count, hemoglobin fractionation, complete metabolic profile
• Другое Control group
  Participants randomized to the control group will be followed per SOC. SOC management for pregnant women with SCD includes but is not limited to * Clinic appointments with an SCD provider every 2 months * Lab draws - complete blood count, reticulocyte count, hemoglobin fractionation, complete metabolic profile with LDH and ferritin.

Первичные конечные точки

• Hospital admissions rate [Срок оценки: Baseline (enrollment) up to 8 weeks post-partum]
• Number of maternal emergency department (ED)/Acute care visits [Срок оценки: Baseline (enrollment) up to 8 weeks post-partum]
• Number of SCD-related complications per group [Срок оценки: Baseline (enrollment) up to 8 weeks post-partum]
• Number of participants with pregnancy related complications [Срок оценки: Baseline (enrollment) up to 8 weeks post-partum]
• Maternal death [Срок оценки: From randomization up to 8 weeks post-partum]

Вторичные конечные точки (11)

• Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) [Срок оценки: 2, 4, 6, 8 and 10 months post randomization.]
• Patient reported outcomes measurement information system (PROMIS) [Срок оценки: 2, 4, 6, 8 and 10 months post randomization.]
• Infant birth weight [Срок оценки: At delivery up to 42 weeks of pregnancy]
• Preterm delivery [Срок оценки: Up to delivery (36 weeks of pregnancy)]
• APGAR Scores [Срок оценки: 1 and 5 minutes after neonate's delivery]
• Number of neonatal intensive care unit/critical care admissions [Срок оценки: After neonate's delivery up to 1 week post-partum]
• Perinatal death [Срок оценки: From 28 weeks of pregnancy up to 1 week post-partum]
• Fetal demise/stillbirth [Срок оценки: From enrollment up to 42 weeks of pregnancy]
• Number of participants with new RBC alloantibodies [Срок оценки: From enrollment up to 8 weeks post-partum]
• Number of participants with transfusion reactions [Срок оценки: From enrollment up to 8 weeks post-partum]
• Number of participants with an increase in iron overload (serum ferritin) [Срок оценки: From enrollment up to 8 weeks post-partum]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Grady Health System — Atlanta

Идентификаторы

NCT: NCT06979492 · STUDY00007288 · 2025P013305

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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