TAPS2 Transfusion Antenatally in Pregnant Women With SCD

Study Overview
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Brief Summary
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Sickle Cell Disease (SCD) is a serious inherited blood disorder affecting red blood cells. When oxygen levels drop the red cells become abnormally shaped and unable to move through the blood vessels easily. Blood and oxygen do not reach body organs, resulting in episodes of severe pain and other complications. Pregnant women with SCD have an increased risk of both sickle and pregnancy complications, including raised blood pressure. Their babies may grow more slowly in the womb, are more likely to be born early and need special care, and have a higher risk of dying. The only treatments currently available for women with SCD are Hydroxycarbamide (which cannot be used during pregnancy) and blood transfusion. Currently, blood transfusion is only used during pregnancy to treat emergency complications. It has been suggested that giving blood transfusions throughout pregnancy could improve outcomes for both mother and babies. In Serial Prophylactic Exchange Blood Transfusion (SPEBT), sickle blood is mechanically removed and simultaneously replaced with donor red cells. A trial is needed to assess SPEBT given every 6-10 weeks, starting before 18 weeks of pregnancy, compared to standard care. This trial will evaluate outcomes for women (e.g. hospital admission, frequency of crisis) and their infants (e.g. early delivery, birthweight). However, the feasibility of such a study needs to be assessed before embarking on a large multicentre trial. This study is therefore a feasibility study in which we will randomly allocate participants to have either SPEBT or standard care. The study will be carried out in multiple maternity units in England and last two years. The willingness of eligible women to join the study will be assessed, along with how many participants remain part of the study until the end and if participants find the intervention acceptable.

Official Title
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A Feasibility Trial of Serial Prophylactic Exchange Blood Transfusion in Pregnant Women With Sickle Cell Disease Aiming to Improve Maternal and Infant Outcomes

Conditions
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Sickle Cell Disease, Pregnancy, High Risk, Blood Transfusion Complication

Intervention / Treatment
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* Biological: Serial prophylactic exchange blood transfusion (SPEBT).


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women with sickle cell disease (all genotypes) Gestation 18+0 weeks or below Willing and able to give informed consent Singleton pregnancy Exclusion Criteria: On long term transfusion programme prior to pregnancy for amelioration of SCD Prior Hyperhaemolysis Red cell phenotype or antibodies present prevent likely provision of adequate red cell units to support elective EBT programme Unable to receive blood transfusion for social, religious or clinical reasons Current diagnosis of major medical or psychiatric comorbidity which in the randomising clinicians opinion renders them unable to enter trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Regular prophylactic blood transfusion given every 6-10 weeks during pregnancy to maintain a HbS% of <30%
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Regular prophylactic blood transfusion given every 6-10 weeks during pregnancy to maintain a HbS% of <30%. | Biological: Serial prophylactic exchange blood transfusion (SPEBT).<br>* Serial prophylactic exchange blood transfusion (SPEBT) will be given via automated apheresis technology. SPEBT will be carried out on the haematology day unit or on the antenatal day unit/ward in accordance with local policies in participating units. The procedure will be carried out using standard operating procedures, by the clinical or research nurse/midwife, haematology day unit staff or specialist sickle nursing staff. Venous access will be via peripheral access if possible or by femoral line access if not. SPEBT will be commenced between 6 and 18+0 weeks gestation. It will be repeated at 6-10 weekly intervals aiming to maintain HbS% <30%. It will continue throughout pregnancy and be stopped at the end of pregnancy. Number of red cell units used per transfusion will depend on patient weight and pre-transfusion HbS%, but will usually be between 6 and 8 units of red cells on each occasion of exchange transfusion.<br>|
| No Intervention: Control<br>Symptom directed blood transfusion during pregnancy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | ratio of women eligible:women randomised | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility endpoints | Number of women eligible, reasons for refusal, rate and reasons for attrition, protocol adherence | up to 6 weeks postpartum | 
| Maternal hospital admissions | Antenatal and postnatal inpatient stays | Every 6-8 weeks from enrolment to 6 weeks postpartum | 
| Frequency and severity of painful crisis | self-reported symptoms (mild/moderate/severe/extremely severe) and use of opioid analgesics | Every 6-8 weeks from enrolment to 6 weeks postpartum | 
| Mode of birth |  | 40 weeks | 
| SCD-related complications | E.g. acute chest syndrome, stroke, pre-eclampsia, venous thromboembolism. | Every 6-8 weeks from enrolment to 6 weeks postpartum | 
| Fetal demise/stillbirth |  | 40 weeks | 
| Infant birthweight | Birthweight in grams | 40 weeks | 
| Gestation at birth | Gestation at birth in completed weeks and days | 40 weeks | 
| Fetal condition at birth | Apgar score at five minutes | 40 weeks | 
| Neonatal intensive care unit/critical care admission |  | 6 weeks postpartum | 
| Safety outcome 1: transfusion reaction |  | Every 6-8 weeks from enrolment to 6 weeks postpartum | 
| Safety outcome 2: Alloimmunisation | Irregular presence of red cell antibodies will be measured by routine blood test | Every 6-8 weeks from enrolment to 6 weeks postpartum | 
| Safety outcome 3: Delayed haemolytic transfusion reaction | After 7 days following transfusion: A. Fatigued, fever, jaundice, dark brown coca-cola urine B. Raised pulse, anaemia C. Dropping Haemoglobin, break down of haemoglobin, increased bilirubin | Every 6-8 weeks from enrolment to 6 weeks postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy, exchange transfusion, perinatal complications