Early Anti-SARS-CoV-2 Convalescent Plasma in Patients Admitted for COVID-19: A Randomized Phase II Clinical Trial

Abstract

Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods: Open-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days or death. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate. Results: Of 58 randomized patients (mean age, 65.8 years, 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion. Conclusion: Immediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration- did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

“…Among them, four studies investigated different doses or durations of administration of the same intervention without comparisons with other interventions or SOC. 45, 46, 64, 71 Eight trials did not specify the outcomes of interest. 55, 58, 68, 81, 93, 101, 122, 123 Treatments in four trials were not connected in the network.…”

Early transfusion of a large cohort of COVID-19 patients with high titer anti-SARS-CoV-2 spike protein IgG convalescent plasma confirms a signal of significantly decreased mortality

“…Similar results were reported for a randomized controlled trial conducted in Chile in which neutralizing antibody titers in donor plasma were not determined prior to transfusion. 19 In contrast, interim analysis of a randomized controlled trial from Spain with 81 randomized patients, reported that no patients progressed to mechanical ventilation or death among the 38 patients receiving convalescent plasma (0%), whereas six of 43 patients (14%) in the control arm did. 18 Mortality rates were 0% versus 9.3% at Days 15 and 29 for the active and control groups, respectively.…”

“…4 Results from three randomized controlled studies and one large observational study have recently been released. 2, 17-19 The PLACID trial found convalescent plasma was not associated with significantly reduced mortality or progression to severe disease. 17 However, resolution of shortness of breath, fatigue, and negative conversion of SARS-CoV-2 viral RNA at Day 7 was higher in the transfused study arm.…”

Clinical Trials in COVID-19 Management & Prevention: A Meta-epidemiological Study examining methodological quality

“…The 91 included trials enrolled a total of 46,802 patients between January 18 (first recruitment) and October 4 (last recruitment). Included trials evaluated one or more drugs (n = 76, )or blood products (n = 9, [88][89][90][91][92][93][94][95][96] ) to treat patients with suspected or confirmed Covid-19 or drugs used as prophylaxis for patients at risk for Covid-19 (n = 6, [97][98][99][100][101][102] ). All but one of the trials were parallel group design (one trial was a cluster randomized design).…”