| Title: |
A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19 |
| Authors: |
Landete, Pedro; Caliman-Sturdza, Olga-Adriana; Lopez-Martin, Jose, A; Preotescu, Liliana; Luca, Mihaela-Catalina; Kotanidou, Anastasia; Villares, Paula; Iglesias, Shirley-Patricia; Guisado-Vasco, Pablo; Saiz-Lou, Elena-Maria; del Carmen Farinas-Alvarez, Maria; de Lucas, Esperanza, Merino; Perez-Alba, Eduardo; Cisneros, Jose-Miguel; Estrada, Vicente; Hidalgo-Tenorio, Carmen; Poulakou, Garyfallia; Torralba, Miguel; Fortun, Jesus; Garcia-Ocana, Paula; Lemaignen, Adrien; Marcos-Martin, Miguel; Molina, Maria; Paredes, Roger; Perez-Rodriguez, Maria, Teresa; Raev, Dimitar; Ryan, Pablo; Meira, Fernanda; Gomez, Javier; Torres, Nadia; Lopez-Mendoza, Diego; Jimeno, Jose; Varona, Jose-Felipe, F |
| Contributors: |
University Hospital October 12; National and Kapodistrian University of Athens (NKUA); Evangelismos Athens General Hospital; Hospital Universitario Quironsalud; Hospital Universitario Virgen de las Nieves Granada, Spain (HUVN); Escuela Andaluza de Salud Publica (Granada.ibs); Universidad de Granada = University of Granada (UGR)-ibs.GRANADA Instituto de Investigación Biosanitaria Granada, Spain; Université de Tours (UT); Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); Éducation Éthique Santé (EES); Centro de Investigaciones sobre Desertificacion (CIDE); Consejo Superior de Investigaciones Cientificas España = Spanish National Research Council Spain (CSIC); Germans Trias i Pujol University Hospital Badalona, Barcelona, Spain (GTPUH); Case Western Reserve University Cleveland; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC); Instituto de Salud Carlos III Madrid (ISCIII); Universitat de VIC, Universitat Central de Catalunyo = University of Vic-Central University of Catalonia (UVic-UCC); Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona (UAB) |
| Source: |
ISSN: 1058-4838. |
| Publisher Information: |
CCSD; Oxford University Press (OUP) |
| Publication Year: |
2024 |
| Collection: |
Université François-Rabelais de Tours: HAL |
| Subject Terms: |
plitidepsin SARS-CoV-2 COVID-19 antiviral agents marine compounds; plitidepsin; SARS-CoV-2; COVID-19; antiviral agents; marine compounds; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Description: |
International audience ; Background. 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. Methods. 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. Results. 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/cid/ciae227 |
| Availability: |
https://hal.science/hal-05538509; https://hal.science/hal-05538509v1/document; https://hal.science/hal-05538509v1/file/plitidepsin%20et%20covid%20CID%202023.pdf; https://doi.org/10.1093/cid/ciae227 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.98E41DCC |
| Database: |
BASE |