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.
Antibodies; COVID-19; Convalescent plasma; Immunity; SARS-CoV-2; Antibodies, Viral; Adult; Antibodies, Viral/blood; Antibodies, Viral/immunology; Belgium/epidemiology; COVID-19/diagnosis; COVID-19/epidemiology; COVID-19/therapy; COVID-19/virology; Combined Modality Therapy/methods; Female; Global Burden of Disease; Hospitalization/trends; Humans; Immunization, Passive/methods; Male; Mortality; Respiration, Artificial/statistics & numerical data; SARS-CoV-2/genetics; SARS-CoV-2/immunology; Safety; Standard of Care/statistics & numerical data; Treatment Outcome; COVID-19 Serotherapy; Belgium; Combined Modality Therapy; Hospitalization; Immunization, Passive; Respiration, Artificial; Standard of Care; Medicine (miscellaneous); Pharmacology (medical)
Abstract :
[en] BACKGROUND: The 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.
METHODS: DAWn-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.
DISCUSSION: This 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 REGISTRATION: ClinicalTrials.gov NCT04429854 . Registered on 12 June 2020 - Retrospectively registered.
Disciplines :
Immunology & infectious disease
Author, co-author :
Devos, Timothy ; University Hospitals Leuven (UZ Leuven), Leuven, Belgium. timothy.devos@uzleuven.be ; Catholic University of Leuven (KU Leuven), Leuven, Belgium. timothy.devos@uzleuven.be
Geukens, Tatjana ; University Hospitals Leuven (UZ Leuven), Leuven, Belgium ; Catholic University of Leuven (KU Leuven), Leuven, Belgium
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.
This published protocol is independent research funded by KCE (Belgian Health Care Knowledge Centre) under the KCE Trials Programme. KCE approved the trial design and protocol but was not involved in the design of the study. KCE will not be involved in data collection, data analysis, data interpretation or writing of manuscripts related to this study.We would like to thank the clinical trial centre of UZ Leuven for their enormous support to make our logistically appalling study up and running in a very limited time-frame. We thank all participating centres and their study teams for their collaboration and efforts. We would like to thank the KCE for their financial support, Rode Kruis-Vlaanderen and Croix Rouge de Belgique for their important contribution and support in this trial, and the four laboratories performing the neutralization tests (REGA institute Leuven, Sciensano, University of Liège and Institute of Tropical Medicine Antwerp). And last but not least, we thank the donors that voluntarily donated convalescent plasma for this trial, as this trial would not have been possible without them.We would like to thank the clinical trial centre of UZ Leuven for their enormous support to make our logistically appalling study up and running in a very limited time-frame. We thank all participating centres and their study teams for their collaboration and efforts. We would like to thank the KCE for their financial support, Rode Kruis-Vlaanderen and Croix Rouge de Belgique for their important contribution and support in this trial, and the four laboratories performing the neutralization tests (REGA institute Leuven, Sciensano, University of Li?ge and Institute of Tropical Medicine Antwerp). And last but not least, we thank the donors that voluntarily donated convalescent plasma for this trial, as this trial would not have been possible without them. In particular, we want to also thank the following people personally: Investigators of participating centres: Dr. Bernard Bouckaert, AZ Delta Roeselare, Roeselare, Belgium Prof Dr. Rik Schots UZ Brussel, Brussels, Belgium Dr. Laurent Jadot, CHC Li?ge Mont L?gia, Li?ge, Belgium Dr. Evelyne Maillart, CHU Brugmann, Brussels, Belgium Dr. Niels Van Regenmortel, ZNA Antwerpen, Antwerp, Belgium Dr. Georgala Aspasia, Institut Jules Bordet, Brussels, Belgium Dr. Clotilde Vis?e, CHR Jolimont Mons-Hainaut, Mons, Belgium Dr. Mathias Leys, AZ Groeninge, Kortrijk, Belgium Dr. Martial Moonen, CHR Citadelle Li?ge, Li?ge, Belgium Dr. Camelia Rossi, CHU Ambroise Par?, Mons, Belgium Dr. Kristof Cuppens, Sint-Trudo Ziekenhuis, Sint-Truiden, Belgium Dr. Emmanuel Van der Hauwaert, Imeldaziekenhuis, Bonheiden, Belgium Dr. Sarah Loof, AZ Maria Middelares, Gent and AZ Sint-Vincentius, Deinze, Belgium Dr. M?lanie Delvallee, Centre Hospitalier de Wallonie Picarde (CHwapi), Tournai, Belgium Coordinators of the DAWn Commando Unit in UZ Leuven, Leuven, Belgium: Dr. Iwein Gyselinck Dr. Matthias Engelen Dr. Laure-Anne Teuwen Dr. Vincent Geldhof Dr. Quentin Van Thillo Dr. Ewout Landeloos Helga Ceunen Barbara Debaveye Other supporting clinicians at UZ Leuven, Leuven, Belgium: Prof. Dr. Peter Vandenberghe Prof. Dr. Kathleen Claes Study coordinators and haemovigilance support for the DAWn-Plasma trial: Elisabeth Porcher Jill Pannecoucke Astrid Thalasso Clinical Trial Center (CTC), UZ Leuven, Leuven, Belgium: Heidi Sterckx Peter Van Rompaey Klara Vlassak Hilde De Tollenaere Jean-Jacques Der?ze Katrien Boulanger Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium: Dr. Frank Hulstaert Hilde Nevens Leuven Coordinating Centre (LCC), Leuven, Belgium Rik Hendrickx Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat) Ann Belmans The following authors wish to acknowledge their funding agencies: TG is funded by the Research Foundation, Flanders (FWO) as a strategic basic research fellow (1S76520N). ND is a post-doctorate clinical master specialist of the F.R.S-FNRS. GM is funded by the Research Foundation, Flanders (FWO) as a senior clinical investigator (1843118?N). Additional collaborators of the DAWn-consortium are listed in the Supplementary Materials.The following authors wish to acknowledge their funding agencies: TG is funded by the Research Foundation, Flanders (FWO) as a strategic basic research fellow (1S76520N). ND is a post-doctorate clinical master specialist of the F.R.S-FNRS. GM is funded by the Research Foundation, Flanders (FWO) as a senior clinical investigator (1843118 N).
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