Abstract
Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200–300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667–1.311); OR for hospitalization or death was 0.919 (CI 0.592–1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394–1.085). CP did not decrease the time to full symptom resolution. Trial registration: Clinicaltrials.gov NCT04621123 and NCT04589949. Registration: NCT04621123 and NCT04589949 on https://www.clinicaltrials.gov
| Original language | English |
|---|---|
| Article number | 2583 |
| Journal | Nature Communications |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec-2022 |
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- 10.1038/s41467-022-29911-3Licence: CC BY
- Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatientsFinal publisher's version, 1.4 MBLicence: CC BY
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In: Nature Communications, Vol. 13, No. 1, 2583, 12.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients
AU - CoV-Early study group
AU - COnV-ert study group
AU - Millat-Martinez, Pere
AU - Gharbharan, Arvind
AU - Alemany, Andrea
AU - Rokx, Casper
AU - Geurtsvankessel, Corine
AU - Papageourgiou, Grigorios
AU - van Geloven, Nan
AU - Jordans, Carlijn
AU - Groeneveld, Geert
AU - Swaneveld, Francis
AU - van der Schoot, Ellen
AU - Corbacho-Monné, Marc
AU - Ouchi, Dan
AU - Piccolo Ferreira, Francini
AU - Malchair, Pierre
AU - Videla, Sebastian
AU - García García, Vanesa
AU - Ruiz-Comellas, Anna
AU - Ramírez-Morros, Anna
AU - Rodriguez Codina, Joana
AU - Amado Simon, Rosa
AU - Grifols, Joan Ramon
AU - Blanco, Julian
AU - Blanco, Ignacio
AU - Ara, Jordi
AU - Bassat, Quique
AU - Clotet, Bonaventura
AU - Baro, Bàrbara
AU - Troxel, Andrea
AU - Zwaginga, Jaap Jan
AU - Mitjà, Oriol
AU - Rijnders, Bart
AU - Gharbharan, Arvind
AU - Rokx, Casper
AU - Jordans, Carlijn
AU - Geurtsvankessel, Corine
AU - Papageourgiou, Grigorios
AU - Rijnders, Bart
AU - Katsikis, Peter
AU - Müller, Yvonne
AU - Koopmans, Marion
AU - Bogers, Susanne
AU - Miedema, Jelle
AU - Russcher, Henk
AU - Scherpenisse, Cees
AU - Postma, Douwe
AU - Koster, David
AU - Lukens, Michaèl
AU - van den Boomgaard, Maartje
AU - Hernández, Luis
N1 - Funding Information: For the CoV-Early study group. The DSMB members for COMPILE (Jan Nouwen, Andrea Troxel, Grigorios Papageorgiou, David Boulware, Josep Puig). All GGD contact tracers who informed potential study candidates. All infectiologists at Erasmus MC who worked even harder during COVID times to let the study team focus on the COVID trials (Adam Anas, Hannelore Bax, Mariana de Mendonça-Melo, Els van Nood, Jan Nouwen, Karin Schurink, Lennert Slobbe, Dorine de Vries-Sluijs) and the ER physicians and collegues from the department of internal medicine who referred patients and facilitated patient recruitment. The medical students who contacted the patients (Romée Land, Eva Pruijt, Silje Taal, Liselotte Jeletich, Willem Sebrechts, Femke de Vries, Tia Rijlaarsdam). The many research assistants, research nurses and other participants who helped in facilitating the study (Maartje Wagemaker, Marita Tjauw Joe Kim—Amadmoestar, Diane Struik, Denise Heida-Peters, Sabine Harinck, Marjo van der Poel, Greetje van Asselt, Danielle Orij—Westerhof, Marloes Romeijn, Marlies Bouterse, Pepita de Vries, Dewi Dubbelaar, Cynthia Oud, Jo Anne den Ouden, Milly Haverkort). Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON) for building the eCRF and providing real-time support with the eCRF on very short notice (Henk Hofwegen, Ronnie van der Holt, Mirjam Stomp, Marleen Luten, Monique Steijart). Professor Eva Petkova at NYU Langone who co-designed the COMPILE concept. All the persons involved in the blinding and distribution of plasma products at the sites. Last but certainly not least, all patients that participated in the trial, the thousands of plasma donors and the COVID test centers who informed patients across the Netherlands about the study. This study was made possible by a research grant from ZONMW, the Netherlands (10430062010001). Sanquin Blood Supply provided convalescent plasma free of charge for study sites in the Netherlands. For the COnV-ert study group. The trial was sponsored by the Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A. and the crowdfunding campaign YoMeCorono ( www.yomecorono.com ). The study received support of the Hospital Universitari Germans Trias i Pujol, and Banc de Sang i Teixits de Catalunya (BST). We thank all the plasma donors and the participants in this study and all the effort they made to attend the visits for follow-up. We thank Gerard Carot-Sans for providing medical writing support with manuscript preparation and Roser Escrig for her support in the study design and medical writing assistance with the study documentation. We also thank Laia Bertran, Mireia Clua, Jordi Mitjà, Claudia Laporte, Sergi Gavilan, Miquel Àngel Rodríguez, Joan Mercado and Enric Nieto for the operational and financial management of the project. We thank the personnel from the Fight Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management. We thank the independent DSMB for their time and dedication: Cinta Hierro (Catalan Institute of Oncology, Badalona, Spain), Natalia Tovar (Hospital Clinic,Barcelona, Spain), Binh Ngo (University of Southern California, Los Angeles, US), David Boulware (University of Minnesota, Minneapolis, US), Robin Mogg (Bill and Melinda Gates Research Institute, Seattle, US). ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). BB was supported by a Beatriu de Pinós postdoctoral fellow granted by the Government of Catalonia’s Secretariat for Universities and Research, and by Marie Sklodowska-Curie Actions COFUND Program (BP3, 801370). EP was supported by a doctoral grant from National Agency for Research and Development of Chile (ANID): 72180406. OM was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program. ZONMW, the Netherlands, grant number 10430062010001. SUPPORT‐E, grant number 101015756. YoMeCorono, www.yomecorono.com . The Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A. The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. home Funding Information: For the CoV-Early study group. The DSMB members for COMPILEhome (Jan Nouwen, Andrea Troxel, Grigorios Papageorgiou, David Boulware, Josep Puig). All GGD contact tracers who informed potential study candidates. All infectiologists at Erasmus MC who worked even harder during COVID times to let the study team focus on the COVID trials (Adam Anas, Hannelore Bax, Mariana de Mendonça-Melo, Els van Nood, Jan Nouwen, Karin Schurink, Lennert Slobbe, Dorine de Vries-Sluijs) and the ER physicians and collegues from the department of internal medicine who referred patients and facilitated patient recruitment. The medical students who contacted the patients (Romée Land, Eva Pruijt, Silje Taal, Liselotte Jeletich, Willem Sebrechts, Femke de Vries, Tia Rijlaarsdam). The many research assistants, research nurses and other participants who helped in facilitating the study (Maartje Wagemaker, Marita Tjauw Joe Kim—Amadmoestar, Diane Struik, Denise Heida-Peters, Sabine Harinck, Marjo van der Poel, Greetje van Asselt, Danielle Orij—Westerhof, Marloes Romeijn, Marlies Bouterse, Pepita de Vries, Dewi Dubbelaar, Cynthia Oud, Jo Anne den Ouden, Milly Haverkort). Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON) for building the eCRF and providing real-time support with the eCRF on very short notice (Henk Hofwegen, Ronnie van der Holt, Mirjam Stomp, Marleen Luten, Monique Steijart). Professor Eva Petkova at NYU Langone who co-designed the COMPILE concept. All the persons involved in the blinding and distribution of plasma products at the sites. Last but certainly not least, all patients that participated in the trial, the thousands of plasma donors and the COVID test centers who informed patients across the Netherlands about the study. This study was made possible by a research grant from ZONMW, the Netherlands (10430062010001). Sanquin Blood Supply provided convalescent plasma free of charge for study sites in the Netherlands. For the COnV-ert study group. The trial was sponsored by the Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A. and the crowdfunding campaign YoMeCorono (www.yomecorono.com). The study received support of the Hospital Universitari Germans Trias i Pujol, and Banc de Sang i Teixits de Catalunya (BST). We thank all the plasma donors and the participants in this study and all the effort they made to attend the visits for follow-up. We thank Gerard Carot-Sans for providing medical writing support with manuscript preparation and Roser Escrig for her support in the study design and medical writing assistance with the study documentation. We also thank Laia Bertran, Mireia Clua, Jordi Mitjà, Claudia Laporte, Sergi Gavilan, Miquel Àngel Rodríguez, Joan Mercado and Enric Nieto for the operational and financial management of the project. We thank the personnel from the Fight Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management. We thank the independent DSMB for their time and dedication: Cinta Hierro (Catalan Institute of Oncology, Badalona, Spain), Natalia Tovar (Hospital Clinic,Barcelona, Spain), Binh Ngo (University of Southern California, Los Angeles, US), David Boulware (University of Minnesota, Minneapolis, US), Robin Mogg (Bill and Melinda Gates Research Institute, Seattle, US). ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). BB was supported by a Beatriu de Pinós postdoctoral fellow granted by the Government of Catalonia’s Secretariat for Universities and Research, and by Marie Sklodowska-Curie Actions COFUND Program (BP3, 801370). EP was supported by a doctoral grant from National Agency for Research and Development of Chile (ANID): 72180406. OM was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program. ZONMW, the Netherlands, grant number 10430062010001. SUPPORT‐E, grant number 101015756. YoMeCorono, www.yomecorono.com. The Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A. The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200–300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667–1.311); OR for hospitalization or death was 0.919 (CI 0.592–1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394–1.085). CP did not decrease the time to full symptom resolution. Trial registration: Clinicaltrials.gov NCT04621123 and NCT04589949. Registration: NCT04621123 and NCT04589949 on https://www.clinicaltrials.gov
AB - Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200–300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667–1.311); OR for hospitalization or death was 0.919 (CI 0.592–1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394–1.085). CP did not decrease the time to full symptom resolution. Trial registration: Clinicaltrials.gov NCT04621123 and NCT04589949. Registration: NCT04621123 and NCT04589949 on https://www.clinicaltrials.gov
U2 - 10.1038/s41467-022-29911-3
DO - 10.1038/s41467-022-29911-3
M3 - Article
C2 - 35546145
AN - SCOPUS:85130639134
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2583
ER -