Safety and Efficacy of Nebulised Anti-Inflammatory Solution of Alkaline Hypertonic Ibuprofen (AHI) for Treatment of SARS-Cov-2 Infection: A Compassionate Study with a Comparator Arms
Galia Kalayan, Ana Carolina Arias Cau, Manuela Del Valle Cabello, Mariela Nuñez, Romina Lumetto, Nicolas Martinez Rios, Luis Argarañas, Néstor García, Roxana Alasino, Dante Beltramo, Roxana Dra, Pabellón Alasino, Ceprocor
European Journal of Respiratory Medicine, doi:10.31488/ejrm.132
Background. This retrospective study evaluates the efficacy of inhalation therapy with alkaline hypertonic ibuprofen (AHI) in COVID-19 positive patients compared to a control group of patients who received conventional treatment. The study was carried out at the Orías Hospital in Jujuy Province, Argentina, from June to September 2020, with final follow-up on September 30. Methods. The study included 99 COVID-19 positive patients with moderate to severe disease (respiratory distress and/or hypoxemia). The control group of 62 patients were treated with the protocols in force at that time, oxygen, dexamethasone and enoxaparin. The group under evaluation comprised 37 patients treated with AH), in addition to standard treatment. Findings. Result shows that the treatment with AHI formulation is safe and effective. The mean respiratory rate (RR) of the patients went from 26.3 before treatment with AHI to 19.8 after treatment. On the other hand, the O2 saturation of patients before treatment with AHI showed a mean of 89.0%; at the end of treatment, the mean was 95.8%. In patients treated with AHI, on day 14, 85% had been discharged, while in patients not treated with AHI, only 36-37% were discharged on day 23. Patients with standard treatment, without AHI, show a mortality of 38.7%, distributed evenly in the 25 days of hospitalization. The mortality of patients treated with AHI was 8.1%, observed within the first 10 days of hospitalization. Interpretation. Results show that nebulization with AHI is an anti-inflammatory therapeutic alternative for the treatment of COVID-19 positive patients.
Declaration of Interests There are no conflicts of interest of the participants of this work to declare.
Contributorship Statement Galia Kalayan coordinated the development and data collection; Ana Carolina Arias Cau, Manuela del Valle Cabello, Mariela Nuñez, Romina Lumetto were the ones who collected the data and made their selection; Dante Beltramo, Roxana Alasino, Luis Argañaras, Néstor García and Nicolás Martinez Rios had the idea for the article; Dante Beltramo and Roxana Alasino wrote the article.
References
Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19-Preliminary Report, New Engl J Med,
doi:10.1056/NEJMoa2007764Cao, Wnag, Wen, A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2001282Capellini, Restini, Bendhack, The Effect of Extracellular pH Changes on Intracellular pH and Nitric Oxide Concentration in Endothelial and Smooth Muscle Cells from Rat Aorta, PlosOne,
doi:10.1371/journal.pone.0062887Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, New Engl J Med,
doi:10.1056/NEJMoa2019014Clemente, Freiberger, Ravetti, An in silico analysis of Ibuprofen enantiomers in high concentrations of sodium chloride with SARS-CoV-2 main protease, J Biomo Structure & Dynamics,
doi:10.1080/07391102.2021.1872420Fang, Jiang, Su, The role of NO in COVID-19 and potential therapeutic strategies, Free Radic Biol Med
Freedman, Loscalzo, Nitric oxide and its relationship to thrombotic disorders, Journal of Thrombosis and Haemostasis
García, Porta, Alasino, Ibuprofen, a traditional drug that may impact the course of COVID-19 New effective formulation in nebulizable solution, Medical Hypotheses
Group, Horby, Estcourt, Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, medRxiv,
doi:10.1101/2021.03.09.21252736Huang, Lin, Chou, Ibuprofen protects ventilator-induced lung injury by downregulating Rho-kinase activity in rats, BioMed Res Int,
doi:10.1155/2014/749097Jiménez, Martin, Pozo, Mechanisms involved in protection afforded by L-arginine in ibuprofen-induced gastric damage: role of nitric oxide and prostaglandins, Dig Dis Sci,
doi:10.1023/a:1013203217788Landray, Recovery, Randomised Evaluation of COVID-19 therapy) Colchicine arm stopped for lack of efficacy in patients hospitalised with COVID-19
Li, Song, Li, Ibuprofen attenuates interleukin-1β-induced inflammation and actin reorganization via modulation of RhoA signaling in rabbit chondrocytes, Acta Biochim Biophys Sin,
doi:10.1093/abbs/gmz101Li, Zhang, Hu, Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19 -A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2020.10044Libster, Marc, Wappner, Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults, N Engl J Med,
doi:10.1056/NEJMoa2033700Monk, Marsden, Tear, Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial, Lancet Respir Med,
doi:10.1016/S2213-2600(20)30511-7Muñoz, Alasino, Garro, High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens, Pharmaceuticals
Onischuk, Tolstikova, An´kov, Ibuprofen, Indomethacin and Diclofenac Sodium Nanoaerosol: Generation, Inhalation Delivery and Biological Effects in Mice and Rats, Journal of Aerosol Science,
doi:10.1016/j.jaerosci.2016.05.005Onischuk, Tolstikova, Sorokina, Analgesic Effect from Ibuprofen Nanoparticles Inhaled by Male Mice, J Aerosol Med Pulmonary Drug Delivery,
doi:10.1089/jamp.2008.0721Pan, Peto, Henao-Restrepo, Repurposed Antiviral Drugs for Covid-19 -Interim WHO Solidarity Trial Results, N Engl J. Med,
doi:10.1056/NEJMoa2023184Perlman, Malik, Ibuprofen prevents thrombin-induced lung vascular injury: mechanism of effect, The Am Physiol Soc. www.physiology.org/journal/ajpheart at Midwestern Univ Lib
Salva Oscar, Roxana, Celia, Nebulization with alkaline hipertonic ibuprofen induces a rapid increase in platelets circulating in COVID-19 patients but not in healthy subjects, Platelets,
doi:10.1080/09537104.2021.1967918.-2021Salva, Doreski, Rersal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program, Infect Dis Ther,
doi:10.1007/s40121-021-00527-2Simonovich, Pratx, Scibona, Plasmar, Group, A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia, N Engl J Med,
doi:10.1056/NEJMoa2031304Veljkovic, Vergara-Alert, Egalés, Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target
Villanueva, Heckenberger, Strobach, Equipotent inhibition by R(-), S(+) and racemic ibuprofen of human polymorphonuclear cell function in vivo, Br J Clin Pharmacol
Wang, Hu, Hu, Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA,
doi:10.1001/jama.2020.1585Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention, JAMA,
doi:10.1001/jama.2020.2648{ 'indexed': {'date-parts': [[2024, 1, 20]], 'date-time': '2024-01-20T12:21:10Z', 'timestamp': 1705753270789},
'reference-count': 0,
'publisher': 'MAK Periodical Library',
'issue': '2',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'DOI': '10.31488/ejrm.132',
'type': 'journal-article',
'created': { 'date-parts': [[2022, 11, 22]],
'date-time': '2022-11-22T17:34:40Z',
'timestamp': 1669138480000},
'source': 'Crossref',
'is-referenced-by-count': 2,
'title': 'Safety and Efficacy of Nebulised Anti-Inflammatory Solution of Alkaline Hypertonic Ibuprofen '
'(AHI) for Treatment of SARS-Cov-2 Infection: A Compassionate Study with a Comparator Arms',
'prefix': '10.31488',
'volume': '4',
'member': '16388',
'published-online': {'date-parts': [[2022]]},
'container-title': 'European Journal of Respiratory Medicine',
'original-title': [],
'deposited': { 'date-parts': [[2022, 11, 22]],
'date-time': '2022-11-22T17:34:46Z',
'timestamp': 1669138486000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://europeanjournalofrespiratorymedicine.com/safety-and-efficacy-of-nebulised-anti-inflammatory-solution-of-alkaline-hypertonic-ibuprofen-ahi-for-treatment-of-sars-cov-2-infection-a-compassionate-study-with-a-comparator-arms'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022]]},
'references-count': 0,
'journal-issue': {'issue': '2', 'published-online': {'date-parts': [[2022]]}},
'URL': 'http://dx.doi.org/10.31488/EJRM.132',
'relation': {},
'ISSN': ['2633-7452'],
'subject': ['General Medicine'],
'container-title-short': 'Eur J Respir Med',
'published': {'date-parts': [[2022]]}}
