ABSTRACT
BackgroundHydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies. MethodsThe Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality. Results1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia. ConclusionsIn patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death. FundingMedical Research Council and NIHR (Grant ref: MC_PC_19056). Trial registrationsThe trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).
ABSTRACT
INTRODUCTION: Current means of assessing women presenting with suspected pre-eclampsia using BP and proteinuria are of limited use in predicting need for imminent delivery. OBJECTIVES/METHOD/DESIGN: We undertook a prospective multicentre study to determine diagnostic accuracy of PlGF <5th centile (Triage assay) and other candidate biomarkers in women presenting with suspected pre-eclampsia at 20-35weeks' gestation, in determining need for delivery for pre-eclampsia within 14days. We calculated ROC curves for predictive potential and undertook principal factor analysis to determine additional predictive ability for biomarker combinations. RESULTS: In 287 women enrolled prior to 35weeks, ROC area (0.88, SE 0.03) for PlGF <5th centile for pre-eclampsia requiring delivery within 14days was greater than all other commonly utilised tests (systolic and diastolic BP, urate, ALT), either singly (range 0.58-0.68), or in combination (0.69) (p<0.001 for all comparisons), and was greater than that of all other biomarkers; addition of 2 other biomarker panels (either procalcitonin, nephrin and BNP; or cystatin and PAPP-A) increased ROC area to 0.90 but these biomarkers had limited predictive ability on their own. CONCLUSION: In women presenting prior to 35weeks' gestation with suspected pre-eclampsia, low PlGF has a greater ROC area than other commonly utilised tests. Additional biomarkers add only a small increment to the predictive value of a single PlGF measurement.
