A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial

Timothy Devos,David Grimaldi,Kevin K Ariën,Daniël Desmecht,Jean Cyr Yombi,Michel Moutschen,Piet Maes,Bart N Lambrecht,Tatjana Geukens,Myriam Cleeren,Cyril Barbezange,Peter Verhamme,Katleen Vandenberghe,Nicolás Dauby ,Johan Van Griensven,Erika Vlieghe,Geert Verbeke,Alexander Schauwvlieghe,Laurens Liesenborghs,Michel Toungouz Névessignsky ,Márta Romano ,Anne Luyten,Veerle Compernolle,Lucie Seyler,Geert Meyfroidt

doi:10.1186/s13063-020-04876-0

Abstract

BackgroundThe COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown.MethodsDAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma.DiscussionThis trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection.Trial registrationClinicalTrials.govNCT04429854. Registered on 12 June 2020 - Retrospectively registered.

Highlights

Background and rationale {6a} In December 2019, the Wuhan Municipal Health Committee identified an outbreak of viral pneumonia cases of unknown cause
Convalescent plasma has proven not to be effective against other viral infections (e.g. Ebola). It carries a risk of antibody-dependent enhancement (ADE), which could result in worsening of the acute respiratory distress syndrome (ARDS), and in Argentine haemorrhagic fever convalescent plasma administration significantly reduced mortality rates, but was found to be associated with a late neurological syndrome [5]
Quality of life (QoL) scoring at day+ 30 is optional if the patient is still hospitalized; if the patient is at home at day+ 30, scoring will be done by telephone call together with or as part of the medical records. It remains the responsibility of the Investigator to check that all data relating to the trial, as specified in the trial protocol, are entered into the electronic case report form (eCRF) in accordance with the instructions provided and that the forms are filled out accurately, completely and in a timely manner

Summary

Introduction

Background and rationale {6a} In December 2019, the Wuhan Municipal Health Committee identified an outbreak of viral pneumonia cases of unknown cause. A recent meta-analysis has shown that convalescent plasma reduces mortality compared to standard of care in patients with SARS and severe influenza infections [4] These studies were heterogeneous on the timing of plasma administration and the threshold on anti-virus antibodies in convalescent donors. The administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this holds true for the novel SARS-CoV-2 virus is currently unknown

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