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

Abstract

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...

Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancies and COVID-19: a longitudinal cohort and propensity score analysis

“…We showed that patients with B-cell lymphoid disease and pre-exposed to anti-CD20 therapy treated with CCP exhibited a significantly better survival probability than those who did not receive CCP. This important finding supports the results reported in a USretrospective cohort 12 as well as the positive trend observed in immunosuppressed patients (odds ratio (OR) 1.51 (0.80 to 2.92)) included in the recently reported REMAP-CAP trial 20 and confirms the essential role of convalescent plasma in the COVID-19 therapeutics landscape of patients with B-cell malignancies.…”

Ocular and Systemic Complications of COVID-19: Impact on Patients and Healthcare

“… 26 In meta-analyses, antiviral antibodies and blood products like convalescent plasma and intravenous immunoglobulins were not associated with a reduction in mortality in those with severe disease. 20 , 27 , 28 The benefits of other treatments like favipiravir, azithromycin, lopinavir-ritonavir, umifenovir are under investigation. 22 …”

Management of COVID patients with convalescent plasma: Do we have the final word?

“…Although CP generally showed a good safety profile, the evidence of relevant clinical benefit in reducing the rate of disease progression or death is scanty and limited to specific subgroups of patients treated early and, in particular, before the development of a serological antibody response. Several randomized clinical trials (RCTs) have been already published [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] [13] [24] or are available as pre-print version [12] , [14] and, with few exception [ 9 , 10 ], they did not show a clear benefit of CP in reducing the risk of disease progression or death ( Table 1 ) . It is noteworthy that, great heterogeneity exists among the available RCTs in terms of enrolled population, timing of plasma infusion, NAbs titer, outcomes and study results.…”

“… [10] Mild/moderate COVID-19 > = 75 years old < =72 h 80/80 Progression to severe respiratory disease (> 30 breaths/min or SaO2< = 93% on room air): 16% vs 31%, p = 0.03 2% vs 5%, RR 0.50, 95% CI 0.09–2.65 (in-hospital) Menichetti et al. (TSUNAMI) [11] Moderate to severe COVID-19 PaO2/FIO2 200–350 < = 10 days (median 7 days) 232/241 Worsening respiratory failure (defined as a PaO2/FiO2 ratio<150) indicating the potential need for mechanical ventilation, or death: 25.5% vs 28%, p = 0.54 6.1% vs 7.9%, p = 0.43 (30-day) REMAP-CAP Investigators [24] Severe COVID-19 median 42 hours ⁎⁎⁎⁎ 1078/909 Organ support–free days up to day 21: 0 vs 3 (median-adjusted OR 0.97 (95% CrI, 0.83 to 1.15) 37.3% vs 38.4% (in-hospital) ⁎ Early vs deferred CP therapy: the early plasma group received the first plasma unit at enrollment. The deferred plasma group received CP only if a prespecified worsening respiratory function criterion was met during hospitalization (PaO2/FiO2 < 200) or if the patient still required hospitalization for symptomatic COVID-19 >7 days after enrollment.…”