Background <p>Pregnancy in women living with sickle cell disease (SCD) is associated with increased risk of morbidity and mortality for mother and baby. Outside of pregnancy, serial prophylactic exchange blood transfusion (SPEBT) has proven efficacy as a treatment for acute SCD complications, however, there is inadequate evidence for the safety and benefit for SCD during pregnancy.</p> Aim <p>To explore health professionals and women’s view on the acceptability and feasibility of a randomised control trial of SPEBT versus usual care in pregnant women with SCD (Transfusion Antenatally in Pregnant women with SCD—TAPS2).</p> Methods <p>Semi-structured telephone interviews were conducted with TAPS2 trial participants, trial decliners and clinical staff working on the TAPS2 trial. Interviews were analysed using reflexive thematic analysis.</p> Results <p>We interviewed 19 trial participants, 12 trial decliners and 15 clinical staff. Three overarching themes were identified. First, factors affecting patient decisions on participation. These included personal benefit, particularly the hope that SPEBT would lead to a healthier pregnancy—and altruistic motivations to help other women with SCD. Factors deterring women from participating included concerns about potential risks of SPEBT, for example infection, side effects, or transfusion reactions. Second, experiences of the TAPS2 trial varied. Participants allocated to SPEBT recounted perceived health benefits as well as ‘expected’ side effects. The time and cost involved in attending transfusion sessions had been difficult for some. Clinical staff at some sites reported that pressures on local apheresis capacity made delivering the intervention challenging. Third, interviews provided recommendations to inform the design of a future definitive RCT of SPEBT versus usual care, including suggestions to maximise participant recruitment. Suggested strategies included the provision of accessible, evidenced-based patient education to patients, partners and families to enable informed decision-making. There was strong support for including an observational arm in any future trial to enable patients unwilling, or unable, to be randomised to take part.</p> Conclusion <p>Patients’ views on blood transfusions emerged as a key determinant in whether they chose to take part in this feasibility trial. Addressing pregnant SCD women’s treatment concerns and preferences is key to maximising recruitment and retention in future trials. Addressing information gaps or misinformation through accessible patient education is needed. Including an observational study arm as part of a future definitive RCT, along with other highlighted strategies, will ensure that the evidence base and understanding of clinical outcomes in pregnant women with SCD is maximised for future research.</p> Trial registration <p>NIH registry (<a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a>), registration number NCT03975894 (registered 05/06/19); ISRCTN (<a href="http://www.isrctn.com">www.isrctn.com</a>), registration number ISRCTN52684446 (retrospectively registered 02/08/19).</p>