Convalescent plasma therapy in COVID-19 critically ill patients during advanced phases of clinical trials and their preliminary results

Abstract

The objective of this study was to highlight the global scientific effort to fight the SARS-CoV-2, addressing the preliminary results of passive immunization through convalescent plasma. We performed a search at the major databases of interventional clinical trial protocols about the transfusion of convalescent plasma in patients with COVID-19, as well as, published articles (n≥25), using the following search strategy: [(COVID-19 OR SARS-CoV-2 OR nCoV-2019) AND (Convalescent plasma OR Plasma exchange) AND (Treatment OR Therapy)]. A total of 24 interventional clinical trial protocols (advanced in phases II-III, III, and IV) were included in this review, as well as three studies that had enough outcomes to evaluate the efficacy of convalescent plasma therapy for patients with COVID-19. All interventional clinical trial protocols applied approximately 500mL of convalescent plasma (from single or more donations) in hospitalized patients, mainly in patients with severe disease associated with standard therapy for COVID-19, and compared to placebo or standard therapy plus specific drugs. Most of interventional clinical trial protocols are multicenter, and the phase IV studies are recruiting at intercontinental centers of North America, Oceania, Europe, but most are recruiting center inside their own county. The three studies published reported similar approach of convalescent plasma intervention with decrease in length of stay, mortality, with less than 4% of adverse events, mainly for treating critical cases with life-threatening disease. All advanced clinical trials focused on convalescent plasma therapy in patients with COVID-19 hospitalized in severe conditions, and the preliminary results provide strong evidence for therapy for the COVID-19 patients.

Figure 1. Analysis of the study progress rate percentile of clinical trial protocols on convalescent plasma therapy for hospitalized patients of COVID-19 distributed by their phases (green bar: phase IV; blue bars: phase III; and red bars: phase II-III) and the corresponding sponsor country

Figure 2. Study design of clinical trials of passive immunization against COVID-19 (plasma therapy), distributed inside out by the different types of allocation (randomized or not), masking (none, single, double, triple, and quadruple blinding), estimated enrollment (varied from 36 to 15,000 individuals), and study countries. The color scale bar represents the number of volunteers estimated in each protocol

Figure 3. The global distribution of clinical trials by phase (circles) and the centers carrying out research on COVID-19 plasma therapy (red bar) and their recruitment centers (cylinders). The main centers of each continent are highlighted in the enlarged image around the central map. Phase IV is indicated by green circle; phase III by blue circle, and phases II-III by red circle. The intercontinental collaborations of the clinical trial protocols at phase IV are represented by the dashed black lines on the world map

Figura 1. Análise do percentual da taxa de progresso do estudo de protocolos de ensaios clínicos sobre terapia de plasma convalescente para pacientes com COVID-19 hospitalizados distribuídos por suas fases (barra verde: fase IV; barras azuis: fase III; e barras vermelhas: fase II-III), com o correspondente país patrocinador

Figura 2. Desenhos de estudo de ensaios clínicos de imunização passiva contra a COVID-19 (terapia com plasma), distribuídos sistematicamente pelos diferentes tipos de alocação (randomizada ou não), mascaramento (nenhum, cegamento único, duplo, triplo e quádruplo), inscrição estimada (variada de 36 a 15 mil indivíduos) e países de estudo. A barra de escala colorida representa o número estimado de voluntários em cada protocolo

Figura 3. Distribuição global dos ensaios clínicos por fase (círculos) e os centros que desenvolvem pesquisas em terapia com plasma para COVID-19 (barra vermelha), além de seus centros de recrutamento (cilindros). Os principais centros de cada continente estão destacados na imagem ampliada em torno do mapa central. Fase IV está indicada por círculo verde; fase III, por círculo azul e fases II-III por círculo vermelho. As colaborações intercontinentais dos protocolos de ensaios clínicos de fase IV estão representadas pelas linhas pretas tracejadas no mapa mundial