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Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial
M. Trøseid, JR. Arribas, L. Assoumou, AR. Holten, J. Poissy, V. Terzić, F. Mazzaferri, JR. Baño, J. Eustace, M. Hites, M. Joannidis, JA. Paiva, J. Reuter, I. Püntmann, TDJH. Patrick-Brown, E. Westerheim, K. Nezvalova-Henriksen, L. Beniguel, TB....
Language English Country England, Great Britain
Document type Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase III, Journal Article
NLK
BioMedCentral
from 1997-04-01
BioMedCentral Open Access
from 1997
Directory of Open Access Journals
from 1998
Free Medical Journals
from 1997
PubMed Central
from 1997
Europe PubMed Central
from 1997
ProQuest Central
from 2015-01-01
Open Access Digital Library
from 1997-01-01
Open Access Digital Library
from 1997-08-01
Open Access Digital Library
from 1998-01-01
Medline Complete (EBSCOhost)
from 2011-02-01
Health & Medicine (ProQuest)
from 2015-01-01
ROAD: Directory of Open Access Scholarly Resources
from 1997
Springer Nature OA/Free Journals
from 1997-04-01
- MeSH
- COVID-19 * MeSH
- Adult MeSH
- Double-Blind Method MeSH
- COVID-19 Drug Treatment MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Viral MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).
Akershus University Hospital Lørenskog Norway
AP HP Hôpital Bichat Service de Maladies Infectieuses Et Tropicales 75018 Paris France
APHP Hôpital Saint Antoine Service de Maladies Infectieuses Et Tropicales 75012 Paris France
Brussels University Hospital Erasme Brussels Belgium
Centre Hospitalier de Luxembourg Service de Réanimation Soins Intensifs 1210 Luxembourg Luxembourg
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas IdiPAZ Madrid Spain
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas Madrid Spain
CIBERINFEC Instituto de Salud Carlos 3 Madrid Spain
CREATIS INSERM U1206 CNRS UMR 5220 Lyon France
Critical Care Center Department of Intensive Care Medicine CHU Lille 59000 Lille France
Department of Acute Medicine Oslo University Hospital Oslo Norway
Department of Anesthesiology and Intensive Care University Hospital of North Norway Tromsø Norway
Department of Clinical Science University of Bergen Bergen Norway
Department of Haematology Oslo University Hospital and Oslo Hospital Pharmacy Oslo Norway
Department of Immunology Oslo University Hospital Oslo Norway
Department of Infectious Diseases Vestfold Hospital Trust Tønsberg Norway
Department of Intensive Care Medicine Stavanger University Hospital Stavanger Norway
Department of Medicine Bærum Hospital Vestre Viken Bærum Norway
Department of Medicine Virgen Macarena University Hospital Seville Spain
Department of Research Support for Clinical Trials Oslo University Hospital Oslo Norway
Deptartment of Infectious Diseases Oslo University Hospital Oslo Norway
Division of Emergencies and Critical Care Oslo University Hospital Oslo Norway
Division of Surgery Inflammatory Diseases and Transplantation Oslo University Hospital Oslo Norway
Faculty of Medicine University of Porto Porto Portugal
Hacettepe University Hospital Ankara Turkey
Hospices Civils de Lyon Département Des Maladies Infectieuses Et Tropicales 69004 Lyon France
Infectious Diseases Unit Internal Medicine Department La Paz University Hospital IdiPAZ Madrid Spain
Infectious Diseases Unit Internal Medicine Department La Paz University Hospital Madrid Spain
Institut National de La Santé Et de La Recherche Médicale INSERM 75013 Paris France
Institute of Clinical Medicine University of Oslo Oslo Norway
Institute of Pharmacology Hospital Group Gesundheit Nord gGmbH Bremen Germany
Intensive Care Medicine Department Centro Hospitalar Universitário Sao Joao Porto Portugal
L'Institut National de La Santé Et de La Recherche Médicale Paris France
Lille University Lille France CHU Lille Hôpital Roger Salengro Lille France
Maladies Infectieuses Emergentes 75015 Paris France
Medical Department Drammen Hospital Vestre Viken Hospital Trust Drammen Norway
Medical University Innsbruck Innsbruck Austria
National and Kapodistrian University of Athens Athens Greece
Norwegian Institute of Public Health Oslo Norway
Research Institute for Internal Medicine Oslo University Hospital Oslo Norway
Research Institute of Internal Medicine Oslo University Hospital Oslo Norway
Research support service and Department of Oncology Oslo University Hospital Oslo Norway
Section for Clinical Immunology and Infectious Diseases Oslo University Hospital Oslo Norway
Section for Monitoring Clinical Trial Unit Oslo University Hospital Oslo Norway
Service de Médecine Intensive Réanimation Hôpital de La Croix Rousse HCL Lyon France
Service de Réanimation Médiale GHRMSA Hopital Emile Muller Mulhouse France
Sorbonne Université INSERM Institut Pierre Louis d'Épidémiologie Et de Santé Publique Paris France
St Anne University Hospital Brno Czech Republic
St Department of Internal Medicine Division of Infectology University of Pécs Pécs Hungary
Université de Paris IAME INSERM 75018 Paris France
Université Libre de Bruxelles Brussels Belgium
University College Cork Cork Ireland
University Hospital of Athens Attikon Athens Greece
University of Sevilla and Biomedicines Institute of Seville CSIC Seville Spain
References provided by Crossref.org
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- $a Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial / $c M. Trøseid, JR. Arribas, L. Assoumou, AR. Holten, J. Poissy, V. Terzić, F. Mazzaferri, JR. Baño, J. Eustace, M. Hites, M. Joannidis, JA. Paiva, J. Reuter, I. Püntmann, TDJH. Patrick-Brown, E. Westerheim, K. Nezvalova-Henriksen, L. Beniguel, TB. Dahl, M. Bouscambert, M. Halanova, Z. Péterfi, S. Tsiodras, M. Rezek, M. Briel, S. Ünal, M. Schlegel, F. Ader, K. Lacombe, CD. Amdal, S. Rodrigues, K. Tonby, A. Gaudet, L. Heggelund, J. Mootien, A. Johannessen, JH. Møller, BD. Pollan, AA. Tveita, AB. Kildal, JC. Richard, O. Dalgard, VC. Simensen, A. Baldé, L. de Gastines, M. Del Álamo, B. Aydin, F. Lund-Johansen, MA. Trabaud, A. Diallo, B. Halvorsen, JA. Røttingen, E. Tacconelli, Y. Yazdanpanah, IC. Olsen, D. Costagliola, EU SolidAct study group
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- $a BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).
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