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Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program

Salva et al., Infectious Diseases and Therapy, doi:10.1007/s40121-021-00527-2, NCT04382768
Aug 2021  
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Mortality, non-MV 45% Improvement Relative Risk Mortality, MV 76% Hospitalization time, non-MV 14% Hospitalization time, MV 18% Ibuprofen for COVID-19  Salva et al.  LATE TREATMENT Is late treatment with ibuprofen + alkalinization beneficial for COVID-19? Retrospective 501 patients in Argentina (April - October 2020) Lower mortality (p=0.0093) and shorter hospitalization (p<0.0001) c19early.org Salva et al., Infectious Diseases and .., Aug 2021 Favorsibuprofen Favorscontrol 0 0.5 1 1.5 2+
Retrospective 383 hospitalized COVID-19 patients in Argentina showing signifcantly lower mortality and shorter hospital stay with nebulized sodium ibuprofenate compared to 195 contemporaneous controls.
The treatment appears to be the same as detailed in1, which reports a pH of 8.5. Kreutzberger et al. showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date.
Baseline SpO2 was significantly different for the patients on mechanical ventilation at baseline.
2 studies use direct respiratory tract administration1,3
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects (early treatment may be more beneficial).
This study is excluded in meta analysis: combined treatments may contribute more to the effect seen.
Study covers ibuprofen and alkalinization.
risk of death, 45.2% lower, RR 0.55, p = 0.009, treatment 35 of 327 (10.7%), control 34 of 174 (19.5%), NNT 11, patients not on mechanical ventilation at baseline.
risk of death, 75.7% lower, RR 0.24, p < 0.001, treatment 11 of 56 (19.6%), control 17 of 21 (81.0%), NNT 1.6, patients on mechanical ventilation at baseline.
hospitalization time, 13.5% lower, relative time 0.86, p < 0.001, treatment mean 11.5 (±0.3) n=327, control mean 13.3 (±0.9) n=174, patients not on mechanical ventilation at baseline.
hospitalization time, 17.8% lower, relative time 0.82, p < 0.001, treatment mean 14.8 (±1.4) n=56, control mean 18.0 (±5.6) n=21, patients on mechanical ventilation at baseline.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Salva et al., 30 Aug 2021, retrospective, Argentina, peer-reviewed, 26 authors, study period 4 April, 2020 - 31 October, 2020, this trial uses multiple treatments in the treatment arm (combined with alkalinization) - results of individual treatments may vary, trial NCT04382768 (history). Contact: garcia.nestor@conicet.gov.ar.
This PaperIbuprofenAll
Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program
Oscar Salva, Pablo A Doreski, Celia S Giler, Dario C Quinodoz, Lucia G Guzmán, Sonia E Muñoz, Mariana N Carrillo, Daniela J Porta, Germán Ambasch, Esteban Coscia, Jorge L Tambini Diaz, Germán D Bueno, Jorge O Fandi, Miriam A Maldonado, Leandro E Peña Chiappero, Fernando Fournier, Hernán A Pérez, Mauro A Quiroga, Javier A Sala Mercado, Carlos Martínez Picco, Marcelo Alejandro Beltrán, Luis A Argañarás, Nicolás Martínez Ríos, Galia I Kalayan, Dante M Beltramo, Néstor H García
Infectious Diseases and Therapy, doi:10.1007/s40121-021-00527-2
Introduction: Sodium ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects, with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients. Methods: NaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care (SOC) to hospitalized COVID-19 patients until oxygen saturation levels of[94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 4 and October 31, 2020, are summarized.
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This funding body had no role in: the design of the ' 'study; the collection, analysis, or interpretation of data; and the writing of ' 'the manuscript. The journal’s Rapid Service Fee was funded by the Química Luar ' 'SRL.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Funding'}}, { 'value': 'All named authors meet the International Committee of Medical Journal Editors ' '(ICMJE) criteria for authorship for this article, take responsibility for the ' 'integrity of the work as a whole, and have given their approval for this ' 'version to be published.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Authorship'}}, { 'value': 'Conceptualization: Pablo Alexis Doreski, Germán Ambasch, Luis Alberto ' 'Argañarás, Nicolás Martínez Ríos, Dante Miguel Beltramo and Néstor Horacio ' 'García. Data curation: Sonia Edith Muñoz, Mariana Natalia Carrillo, Daniela ' 'Josefina Porta, Hernán Alejandro Pérez, Néstor Horacio García. Formal analysis: ' 'Pablo Alexis Doreski, Sonia Edith Muñoz, Mariana Natalia Carrillo, Daniela ' 'Josefina Porta, Hernán Alejandro Pérez, Dante Miguel Beltramo, Néstor Horacio ' 'García. Funding acquisition: Luis Alberto Argañarás, Nicolás Martínez Ríos and ' 'Galia Ines Kalayan. Investigation: Oscar Salva, Celia Sara Giler, Dario Conrado ' 'Quinodoz, Lucia Guadalupe Guzmán, Germán Ambasch, Esteban Coscia, Jorge Luis ' 'Tambini Díaz, Germán David Bueno, Jorge Oscar Fandi, Miriam Angélica Maldonado, ' 'Leandro Eugenio Peña Chiappero, Fernando Fournier, Hernán Alejandro Pérez, ' 'Mauro Andrés Quiroga, Javier Agustín Sala Mercado, Marcelo Alejandro Beltrán, ' 'Carlos Martínez Picco, Methodology: Luis Alberto Argañarás, Nicolás Martínez ' 'Ríos, Dante Miguel Beltramo, Néstor Horacio García. Project administration: ' 'Luis Alberto Argañarás, Nicolás Martínez Ríos, Galia Inés Kalayan. Resources: ' 'Luis Alberto Argañarás and Nicolás Martínez Ríos. Supervision: Luis Alberto ' 'Argañarás, Nicolás Martínez Ríos, Néstor Horacio García. Software: Hernán ' 'Alejandro Pérez. Validation: Oscar Salva, Pablo Alexis Doreski, Néstor Horacio ' 'García. Visualization: Néstor Horacio García. Writing—original draft: Néstor ' 'Horacio García. Writing—review and editing: Pablo Alexis Doreski, Dario Conrado ' 'Quinodoz, Luis Alberto Argañarás, Nicolás Martínez Ríos, Dante Miguel Beltramo, ' 'Néstor Horacio García.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Authorship Contributions'}}, { 'value': 'All named authors confirm that they have no conflicts of interest to declare.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Disclosures'}}, { 'value': 'Ethical approval was obtained from the Institutional Independent Ethics ' 'Committees and district regulatory agencies of Córdoba and Mendoza Provinces ' 'for the compassionate use of Luarprofeno<sup>®</sup> (sodium ibuprofenate in ' 'hypertonic saline, or NaIHS, for nebulization). The program was carried out in ' 'accordance with the principles of the Declaration of Helsinki for Buenos Aires. ' 'All participating individuals were ≥ age 18 and provided written informed ' 'consent, obtained by the treating physician.', 'order': 5, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Compliance with Ethics Guidelines'}}, { 'value': 'The datasets used and analyzed during the current study are available from the ' 'corresponding author in response to reasonable requests.', 'order': 6, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Data Availability'}}]}
Late treatment
is less effective
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