Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO 2 Requirements.

Autor:	Neuenschwander FC; Núcleo de Pesquisa Clínica-Hospital Vera Cruz, Belo Horizonte 30190-130, Brazil., Barnett-Griness O; Bioforum Ltd., Ness Ziona 7403636, Israel., Piconi S; Ospedale A. Manzoni, 23900 Lecco, Italy., Maor Y; Infectious Disease Unit, E. Wolfson Medical Center, Holon 58100, Israel.; Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel., Sprinz E; Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil., Assy N; Western Galilee Medical Center, Nahariya 221001, Israel., Khmelnitskiy O; Saint-Petersburg State Budget Healthcare Institution 'City Pokrovskaya Hospital', Saint-Petersburg 199106, Russia., Lomakin NV; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow 121359, Russia., Goloshchekin BM; Saint-Petersburg SBHI City Hospital 15, Saint-Petersburg 197110, Russia., Nahorecka E; Zespół Opieki Zdrowotnej, 59-700 Bolesławiec, Poland., Joaquim Westheimer Calvacante A; CEMEC-Centro Multidisciplinar de Estudos Clinicos LTDA, São Bernardo do Campo 09715-090, Brazil., Ivanova A; State Budgetary Institution of Ryazan Region 'Regional Clinical Hospital', Ryazan 390026, Russia., Vladimirovich Zhuravel S; N.V. Sklifosovsky Research Institute for Emergency Medicine of Health Department of Moscow, Moscow 129090, Russia., Yurevna Trufanova G; State Budgetary Healthcare Institution of the Tver Region 'Regional Clinical Hospital', Tver 170100, Russia., Bonora S; Ospedale Amedeo di Savoia, 10149 Torino, Italy., Saffoury A; Nazareth Hospital EMMS, Nazareth 19152, Israel., Mayo A; Assuta Medical Center Ashdod, Ashdod 7747629, Israel., Shvarts YG; Clinical Hospital n.a-S.R. Mirotvortseva SSMU, Saratov 410012, Russia., Rizzardini G; Ospedale Luigi Sacco, 20157 Milan, Italy., Sobroza de Mello R; Hospital Nossa Senhora da Conceição de Tubarão, Centro de Pesquisas Clínicas do Hospital Nossa Senhora da Conceição, Tubarão 88701-160, Brazil., Pilau J; Hospital de Clínicas de Passo Fundo, Cento de Pesquisa Clínica, Passo Fundo 99010-260, Brazil., Klinov A; Kirovsk Interregional Hospital, Leningrad 187342, Russia., Valente-Acosta B; Hospital ABC, Mexico City 05348, Mexico., Olegovich Burlaka O; Saint-Petersburg State Budgetary Healthcare Institution 'City Aleksandrovskaya Hospital', Saint-Petersburg 193312, Russia., Bakhtina N; State Regional Budgetary Healthcare Institution Murmansk Regional Clinical Hospital, Murmansk 183032, Russia., Bar-Meir M; Shaare Zedek Medical Center, Jerusalem 9103102, Israel., Nikolaevich Shishimorov I; Department of Pediatrics and Neonatology, Institute of Medical and Physiotherapy, Federal State Budgetary Educational Institution of Higher Education Volgograd State Medical University, Volgograd 400087, Russia., Oñate-Gutierrez J; Centro Medico Imbanaco de Cali, Valle del Cauca 760042, Colombia., García Rincón CI; Unidad de Transferencia y Ensayos Clínicos Clinica Universitaria Bolivariana, Medellin 050021, Colombia., Ivanovna Martynenko T; Regional State Budgetary Healthcare Institution 'City Hospital No. 5, Barnaul', Barnaul 656045, Russia., Hajjar LA; Instituto do Coração do Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Andar 05403-900, Brazil., Carolina Nazare de Mendonca Procopio A; Hospital Felicio Rosso, Belo Horizonte 30110-934, Brazil., Simon K; Szpital Specjalistyczny im. Gromkowskiego, 51-149 Wrocław, Poland., Gabriel Chaves Santiago W; Sociedad de Cirugía de Bogotá Hospital de San José, Bogota 110821, Colombia., Fronczak A; Centrum Onkologii w Lodzi, Oddzial COVID-19, 93-510 Lodz, Poland., Roberto Hoffmann Filho C; Hospital Regional Hans Dieter Schmidt, Joinville 89227-680, Brazil., Hussein O; Ziv Medical Center, Safed 13100, Israel., Aleksandrovich Martynov V; State Budgetary Healthcare Institution of the Tver Region 'Regional Clinical Hospital', Ryazan 390026, Russia., Chichino G; Azienda Ospedaliera SS, 15121 Alessandria, Italy., Blewaska P; Szpital Rejonowy w Raciborzu, 47-400 Racibórz, Poland., Wroblewski J; Szpital Wojewódzki im. Mikołaja Kopernika, 75-581 Koszalin, Poland., Saul Irizar Santana S; Hospital Civil de Culiacan, Sinaloa 80030, Mexico., Felipe Ocampo Agudelo A; Fundacion Hospitalaria San Vicente, Antioquia 050001, Colombia., Barczyk A; Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, 40-055 Katowice, Poland., Lask Gerlach R; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel., Campbell E; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel., Bibliowicz A; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel., Fathi R; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel., Anderson P; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel., Raday G; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel., Klein M; Bioforum Ltd., Ness Ziona 7403636, Israel., Fehrmann C; CEEF Solutions Beaconsfield, Pointe-Claire, QC H9S 4L7, Canada., Eagle G; G.E.T. Pharma Consulting, LLC, Lumberville, PA 18933, USA., Ben-Yair VK; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel., Levitt ML; RedHill Biopharma Ltd., Tel-Aviv 6473921, Israel.
Jazyk:	angličtina
Zdroj:	Microorganisms [Microorganisms] 2024 Aug 26; Vol. 12 (9). Date of Electronic Publication: 2024 Aug 26.
DOI:	10.3390/microorganisms12091767
Abstrakt:	Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO 2 ) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO 2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO 2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p -value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p -value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p -value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO 2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.
Databáze:	MEDLINE
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