Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Landray, Martin J; Horby, Peter; Emberson, Jonathan; Staplin, Natalie; Spata, Enti; Pessoa-Amorim, Guilherme; Peto, Leon; Mafham, Marion; Haynes, Richard

doi:10.1016/s0140-6736(21)00897-7

Cited by 391 publications

(290 citation statements)

References 29 publications

Supporting

Mentioning

272

Contrasting

Unclassified

Order By: Relevance

“…Qualitative inspection of the available Kaplan–Meier survival data from 16 controlled studies revealed a directionally consistent pattern whereby convalescent plasma transfusion was associated with greater patient survival compared to non-transfused patients ( Figure 1 ) ( 11 , 27 , 41 , 43 , 46 , 47 , 50 , 52 , 59 – 62 , 64 , 69 – 71 ). Pooling all available Kaplan–Meier survival data showed a 14% relative improvement in COVID-19 patient 28-day survival associated with convalescent plasma (84 vs. 74%) ( Figure 2A ).…”

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 98%

“…To date, 11 RCTs ( 11 , 27 , 30 , 40 – 47 ) and 24 matched-control studies ( 3 , 4 , 48 – 69 ) have investigated convalescent plasma therapy for COVID-19. Of these studies, 16 presented survival data using a Kaplan–Meier diagram ( 11 , 27 , 41 , 43 , 46 , 47 , 50 , 52 , 59 – 62 , 64 , 69 – 71 ). To investigate the impact of convalescent plasma on COVID-19 patient survival over time, we extracted daily survival data from all available Kaplan–Meier diagrams using an online data extraction tool (WebPlotDigitizer v4.4, Pacifica, CA, USA).…”

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

“…Pooling all available Kaplan–Meier survival data showed a 14% relative improvement in COVID-19 patient 28-day survival associated with convalescent plasma (84 vs. 74%) ( Figure 2A ). We offer the caveat that due to the large sample size of the RECOVERY Trial ( 11 ), these data were not included in this aggregation but reported separately ( Figure 2D ). The RECOVERY Trial found no difference in 28-day mortality between COVID-19 patients treated with convalescent plasma and non-transfused patients (24 vs. 24%) ( 11 ).…”

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

“…We offer the caveat that due to the large sample size of the RECOVERY Trial ( 11 ), these data were not included in this aggregation but reported separately ( Figure 2D ). The RECOVERY Trial found no difference in 28-day mortality between COVID-19 patients treated with convalescent plasma and non-transfused patients (24 vs. 24%) ( 11 ). The general survival benefit associated with convalescent plasma has been observed worldwide including studies that were heterogenous for health system type and infectious disease or critical care infrastructure, timing relative to pandemic onset, convalescent plasma antibody titer and volume, and patient disease severity ( Supplementary Figure 1 ).…”

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

“…Conversely, recent reviews that adhered to stricter study inclusion rules and aggregated only RCT data concluded that either convalescent plasma had no effect on mortality or that insufficient evidence exists to determine efficacy ( 9 , 10 ). In addition, data emerging from the RECOVERY Trial in the United Kingdom showed no survival benefit of convalescent plasma in its overall cohort that was severely ill but demonstrated trends toward efficacy when plasma was transfused to patients who were earlier in the disease course and did not require supplemental oxygen or corticosteroids ( 11 ). These contradictory findings present a challenge for physicians in deciding the therapeutic strategy for COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

et al. 2021

View full text Add to dashboard Cite

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan–Meier survival plots. Qualitative inspection of all available Kaplan–Meier survival data and an aggregate Kaplan–Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.

show abstract

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 98%

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

et al. 2021

View full text Add to dashboard Cite

show abstract

Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19

Abdel‐Hady¹,

Abdelrazik²,

Abdi³

et al. 2021

JAMA

Self Cite

164

134

View full text Add to dashboard Cite

Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

show abstract

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients

et al. 2022

View full text Add to dashboard Cite

Key Points Question Does COVID-19 convalescent plasma (CCP), compared with placebo, improve the clinical status of hospitalized patients with COVID-19 requiring noninvasive supplemental oxygen? Findings In this randomized clinical trial including 941 patients, based on the World Health Organization 11-point Ordinal Scale for Clinical Improvement, CCP did not benefit 468 participants randomized to CCP compared with 473 randomized to placebo from April 2020 to March 2021. However, in exploratory analyses, CCP appeared to benefit those enrolled from April to June 2020, the period when most participants received high-titer CCP and were not receiving remdesivir and corticosteroids at randomization. Meaning In this trial, CCP did not meet prespecified outcomes for efficacy, but high-titer CCP may have benefited hospitalized patients with COVID-19 early in the pandemic when other treatments were not in use, suggesting a heterogenous treatment effect over time.

show abstract

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Cited by 391 publications

References 29 publications

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients

Contact Info

Product

Resources

About