A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19
Landete, Pedro (Hospital Universitario de la Princesa (Madrid))
Caliman-Sturdza, Olga-Adriana (University of Suceava)
Lopez-Martin, Jose A (PharmaMar (Madrid))
Preotescu, Liliana (University of Medicine and Pharmacy "Carol Davila" (Bucarest, Romania))
Luca, Mihaela-Catalina ("Grigore T. Popa" University (Iasi, Romania))
Kotanidou, Anastasia (National and Kapodistrian University of Athens)
Villares, Paula (Hospital Universitario HM Sanchinarro (Madrid))
Iglesias, Shirley-Patricia (Clinica de la Costa (Barranquilla, Colòmbia))
Guisado-Vasco, Pablo (Hospital Universitario Quironsalud Madrid)
Saiz-Lou, Elena-Maria (PPharmaMar (Madrid))
Del Carmen Farinas-Alvarez, Maria (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Merino de Lucas, Esperanza (Hospital General Universitari d'Alacant)
Cisneros, José Miguel (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Estrada, Vicente (Hospital Clínico San Carlos (Madrid))
Hidalgo-Tenorio, Carmen (Hospital Universitario Virgen de las Nieves (Granada))
Poulakou, Garyfallia (National Sotiria General Hospital (Atenes, Grècia))
Torralba, Miguel (Guadalajara University Hospital)
Fortún, Jesús (Hospital Universitario Ramón y Cajal (Madrid))
Garcia-Ocana, Paula (Centre Hospitalier Regional et Universitaire de Tours (CHRU Tours)-Hopital Bretonneautu)
Lemaignen, Adrien (Hospital Universitario de Jerez (Jerez de la Frontera))
Marcos-Martin, Miguel (Hospital Universitario de Salamanca)
Molina Simón, María (Hospital Universitari de Bellvitge)
Paredes, Roger (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Perez-Rodriguez, Maria Teresa (Complexo Hospitalario Universitario de Vigo)
Raev, Dimitar (University Hospital UMHAT "Sveta Anna" (Sofia, Bulgaria))
Ryan, Pablo (Hospital Universitario Infanta Leonor)
Gomez, Javier (PharmaMar (Madrid))
Torres, Nadia (PharmaMar (Madrid))
Lopez-Mendoza, Diego (PharmaMar (Madrid))
Jimeno, Jose (PharmaMar (Madrid))
Varona, Jose F (Hospital Universitario HM Monteprincipe (Madrid))
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1. 5 mg/day or 2. 5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio, 1. 37; 95% confidence interval,. 96-1. 96; P =. 08 for plitidepsin 1. 5 mg vs control; hazard ratio, 1. 06; 95% confidence interval,. 73-1. 53; P =. 78 for plitidepsin 2. 5 mg vs control). Plitidepsin was generally well tolerated. Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Plitidepsin ; SARS-CoV-2 ; COVID-19 ; Antiviral agents ; Marine compounds
Publicat a:	Clinical infectious diseases (University of Chicago. Press), Vol. 79 (august 2024) , p. 910-919, ISSN 1537-6591

DOI: 10.1093/cid/ciae227
PMID: 39182994

10 p, 587.2 KB

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