NEPTUNO (high-dose plitidepsin)
Trial question
What is the role of plitidepsin in hospitalized patients with moderate COVID-19 infection?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 135
135 patients (50 female, 85 male).
Inclusion criteria: hospitalized adult patients with moderate COVID-19 infection.
Key exclusion criteria: baseline impairment in general health condition for whatever reason except COVID-19; requirement of severe dependency for daily living activities or chronic oxygen therapy; evidence of respiratory failure at the time of randomization; severe COVID-19; concomitant antiviral, immunomodulatory, or immunosuppressive therapies at the time of randomization.
Interventions
N=68 plitidepsin (at an intravenous dose of 2.5 mg/day for 3 days and at least 3 days of dexamethasone).
N=67 standard of care (regulatory-approved antiviral treatment, such as remdesivir 100-200 mg IV or favipiravir 600-1,600 mg PO BID).
Primary outcome
Median time to sustained withdrawal of supplemental oxygen
5 days
7 days
7.0 days
5.3 days
3.5 days
1.8 days
0.0 days
Plitidepsin
Standard of
care
No significant
difference ↔
No significant difference in median time to sustained withdrawal of supplemental oxygen (5 days vs. 7 days; HR 1.06, 95% CI 0.73 to 1.53).
Secondary outcomes
No significant difference in median time to sustained hospital discharge (7 days vs. 7 days; HR 0.95, 95% CI 0.66 to 1.37).
No significant difference in 11-point WHO Clinical Progression Scale Clinical Status 0-2 at day 8 (60.3% vs. 52.3%; OR 1.12, 95% CI 0.6 to 2.06).
No significant difference in the rate of requirement of ICU admission until day 8 (11.1% vs. 6.2%; OR 1.94, 95% CI 0.54 to 7.04).
Safety outcomes
No significant differences in grade ≥ 3 treatment-emergent adverse events, treatment-related treatment-emergent adverse events.
Conclusion
In hospitalized adult patients with moderate COVID-19 infection, plitidepsin was not superior to standard of care with respect to median time to sustained withdrawal of supplemental oxygen.
Reference
Pedro Landete, Olga-Adriana Caliman-Sturdza, Jose A Lopez-Martin et al. A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19. Clin Infect Dis. 2024 Oct 15;79(4):910-919.
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