Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 patients. A controlled clinical trial
Jose Lenin Beltran Gonzalez, MD Mario González Gámez, Emmanuel Antonio Mendoza Enciso, MD Ramiro Josue Esparza Maldonado, MD Daniel Hernández Palacios, Samuel Dueñas Campos, MD Itzel Ovalle Robles, MD Mariana Jocelyn Macías Guzmán, Andrea Lucia García Díaz, César Mauricio Gutiérrez Peña, MD Ana Lilian Reza-Escalera, MD Maria Teresa Tiscareño Gutierrez, Elva Galvan-Guerra, Maria Del Rocio Dorantes Morales, MD Lucila Martínez Medina, Victor Antonio Monroy Colin, Arreola Guerra Jose Manuel
doi:10.1101/2021.03.28.21254507
Background The proportion of critically ill COVID-19 patients has collapsed hospital care worldwide. The need for alternative therapies for this group of patients is imperative. This study aims to compare the safety and efficacy of convalescent plasma (CP) compared with human immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or mechanical ventilation.
Methods This is a controlled, randomized, open clinical trial of patients with pneumonia secondary to SARS-CoV-2 infection, that fulfilled criteria for severe or critical disease. They were randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram of ideal weight, in an 8-hour infusion every 24 hours, for 5 days. Group 2 was administered 200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of hospitalization and mortality at 28 days.
Results: One hundred and ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their average age was 58 years (IQR 47 -72), and most were male (n= 119, 62.6 %). On inclusion, 85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 -26). Mortality at 28 days was 45.2 % (n=86). In the intention-to-treat analysis, there was no difference between groups neither in mortality on follow-up (53.8 vs. 53.3, p =1.0) nor at 28 days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per-protocol analysis between treatment groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP group received plasma with detectable anti-SARS-CoV-2 antibodies.
Conclusions: In critically ill patients or on invasive mechanical ventilation for treatment of Covid-19, the use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use of CP is based on complex logistics and requires an assured level of antibodies if used therapeutically. IVIg does not appear to be useful in this group of patients. clinicaltrials.gov identifier: NCT04381858.
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'abstract': '<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The '
'proportion of critically ill COVID-19 patients has collapsed hospital care worldwide. The '
'need for alternative therapies for this group of patients is imperative. This study aims to '
'compare the safety and efficacy of convalescent plasma (CP) compared with human '
'immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or '
'mechanical '
'ventilation.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This is a '
'controlled, randomized, open clinical trial of patients with pneumonia secondary to '
'SARS-CoV-2 infection, that fulfilled criteria for severe or critical disease. They were '
'randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram '
'of ideal weight, in an 8-hour infusion every 24 hours, for 5 days. Group 2 was administered '
'200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of '
'hospitalization and mortality at 28 '
'days.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>One hundred and '
'ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their '
'average age was 58 years (IQR 47 – 72), and most were male (n= 119, 62.6 %). On inclusion, '
'85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality '
'in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 – 26). '
'Mortality at 28 days was 45.2 % (n=86). In the intention-to-treat analysis, there was no '
'difference between groups neither in mortality on follow-up (53.8 vs. 53.3, p =1.0) nor at 28 '
'days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per-protocol analysis between treatment '
'groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) '
'nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP '
'group received plasma with detectable anti-SARS-CoV-2 '
'antibodies.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In '
'critically ill patients or on invasive mechanical ventilation for treatment of Covid-19, the '
'use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use '
'of CP is based on complex logistics and requires an assured level of antibodies if used '
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