Prophylactic exchange transfusion in sickle cell disease pregnancy: a TAPS2 feasibility randomized controlled trial.

ABSTRACT: Serial prophylactic exchange blood transfusion (SPEBT) is increasingly used in sickle cell disease (SCD) pregnancy, despite a lack of robust evidence. The Transfusion Antenatally in Pregnant Women with Sickle Cell Disease (TAPS2) study assessed the feasibility and acceptability of conducting a definitive randomized controlled trial of SPEBT (intervention) vs standard care (control) in this population. Women aged ≥18 years with SCD, between 6+0 and 18+6 weeks of singleton gestation, were randomized 1:1 every 6 -10 weeks throughout pregnancy in 7 hospitals in England. The main outcomes were recruitment rate (primary outcome), acceptability, and retention. Secondary outcomes were safety and maternal/infant outcomes. In total, 194 women were screened over 42 months (extended because of the pandemic), 88 were eligible, and 35 (39.8%) consented to participate; 18 participants were randomized to intervention, and 17 to control. Follow-up data were collected on all participants. Twelve patients in the intervention group received at least 1 SPEBT, of these, 11 received ≥3. The remaining patient was withdrawn from SPEBT because of transfusion reaction. Sixteen control participants required at least 1 transfusion. There were no statistically significant differences in maternal, infant, and postnatal outcomes. A trend toward a lower incidence of vaso-occlusive crisis, preterm delivery, and improved birthweight was observed in the intervention. The study achieved satisfactory recruitment and retention, confirming its acceptability to participants. TAPS2 demonstrates that it is feasible to perform a definitive international trial of SPEBT in SCD pregnancy. These trials were registered at www.ClinicalTrials.gov as #NCT03975894 and International Standard Randomized Controlled Trial Number (www.isrctn.com; #ISRCTN52684446).

Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): statistical and qualitative analysis plan for a randomised controlled feasibility trial.

BACKGROUND: There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study. METHODS AND DESIGN: TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6-10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes. RESULTS: Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update. CONCLUSION: The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias. TRIAL REGISTRATION: NIH registry ( www. CLINICALTRIALS: gov ), registration number NCT03975894 (registered 05/06/19); ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).