Background
Summary of findings from previous clinical trials and systematic reviews
Methods/Design
Aim
Objectives | ||
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Trial | Feasibility: primary | 1. Assess the willingness of pregnant women with SCD to take part in a randomised controlled trial comparing SPEBT to standard care. |
Feasibility: secondary | 2. Identify barriers and facilitators to participation in the trial, including assessing reasons for refusal. 3. Assess retention rates of participants throughout pregnancy in both arms of the study. 4. Assess the willingness of clinicians to recruit into this trial. | |
Clinical: infant | 5. Assess the proportion from the control arm advised clinically to start prophylactic blood transfusion. 6. Measure clinical outcomes for women and infants including an initial preliminary assessment of efficacy for future definitive trial. 7. Generate data to inform the design of a definitive trial, including identifying the primary outcome. | |
Clinical: maternal | ||
Safety | 8. Record safety issues around blood transfusions in both arms of the study | |
Qualitative | Feasibility | 9. Identify barriers and facilitators to participation from study participants, clinicians and, where possible, those unwilling to participate 10. Identify strategies to optimise recruitment and retention 11. Assess acceptability of the intervention, trial procedures and study conduct, including identifying the core outcomes that are considered important to measure and preference for either HRQOL measure 12. Identify reasons for attrition 13. Assess women’s experience of taking part in the study |
Economic | Resource Use & Costs | 14. Explore the cost implications of the proposed intervention and to assess measurement tools and methods |
HRQoL & health benefits | 15. Assess two widely used HRQoL measures against each other and other health benefits |
Design and setting
Participants
Exclusion criteria
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Unable or unwilling to give written informed consent
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On long-term transfusion programme prior to pregnancy for the amelioration of SCD
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Unable to receive blood transfusion for social, clinical or religious reasons
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Current diagnosis of major medical or psychiatric comorbidity that, in the randomising clinicians’ opinion, renders them unable to enter the trial
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Prior hyperhaemolysis
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Red cell phenotype or antibodies present prevent likely provision of adequate red cell units to support elective EBT programme
Participant identification and recruitment
Randomisation
Standard care
Intervention
Data collection
Outcomes
Primary outcome
Secondary outcomes
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The number of women screened who meet the study eligibility criteria
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Reasons for eligible women declining participation
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Rate and reasons for attrition (monitored by assessing the number of women completing the study, and by reporting reasons given (if any) for study drop-out)
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Protocol adherence (measured by the number of women allocated to the intervention group who receive SPEBT as intended (beginning < 18 weeks, transfusions every 6–10 weeks, to maintain a HbS < 30% or combined HbS & HbC < 30%), and the number of women in the standard care group who receive a transfusion due to clinical need)
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Patient experience and acceptability (assessed through qualitative methods)
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Views and experiences of clinical staff caring for women in both arms of the trial (assessed through qualitative methods)
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Neonatal: Foetal demise/stillbirth/neonatal death, Apgar score at 5 min, birthweight, gestation at birth, NICU/SCBU admission with reason and length of stay, feeding method at discharge
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Maternal: Antenatal hospital admissions and critical care admissions, length of stay (total inpatient, antenatal and postnatal nights), frequency and severity of painful crisis (severity of crisis will be measured as mild, moderate, severe or extremely severe, where mild crises may or may not have required pain medication but did not prevent normal activity, moderate crises required medication and caused significant changes in daily activities, severe crises required attendance at hospital, and extremely severe required hospital admission); use of opioid analgesics (excluding labour); frequency of SCD-related complications (acute chest syndrome, pre-eclampsia); number and reason for any transfusion (in the standard care arm); number of transfusions (in the intervention arm), mode of birth, and estimated blood loss; postnatal health and complications, including pain and primary and secondary postpartum haemorrhage; and hospital readmission after postnatal discharge, thromboembolism, infection, or depression
Health economic sub-study
Nested qualitative study
Trial withdrawal or discontinuation
Power and sample size
Analysis
Ethical considerations and confidentiality
Patient and public involvement
Trial governance and monitoring
Progression to a full trial
Recruitment rate of eligible participants (measuring reach, acceptability) | Frequency of SPEBT (measuring dose, acceptability) | Retention until 6 weeks post-delivery (measuring acceptability) | Findings from qualitative study and acceptability | |
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Green | ≥ 50% | ≥ 75%, three or more | ≥ 80% | Progress but will use findings from qualitative study to inform and improve definitive RCT |
Yellow | 30–50% | 50–75%, three or more | 50–80% | Use findings from qualitative study to inform progressing to definitive study depending on guidance from trial steering committee, Sickle Cell Society, PPI group and key stakeholders |
Red | < 30% | < 50%, three or more | < 50% | Will not progress |