Covid-19 Living Data

Trial NCT05205759
Publication MANTICO - Mazzaferri F, eLife (2022) (published paper)
Dates: 2021-12-09 to 2022-01-20
Funding: Public/non profit (Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA); the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union’s Horizon 2020 research and innovation programme)
Conflict of interest: No

Methods
	RCT Blinding: single blinding
	Location : Multicenter / Italy Follow-up duration (days): 28
Inclusion criteria	Outpatients aged 50 years or older presenting with a positive test (either direct antigen or nucleic acid SARS-CoV-2) mild to moderate COVID-19 symptoms within 4 days of the onset - cough, nasal congestion, sore throat, feeling hot or feverish, myalgia, fatigue, headache, anosmia/ageusia, nausea, vomiting, and/or diarrhoea
Exclusion criteria	Peripheral oxygen saturation level of 93% or less on room air respiratory rate of 30 or more breaths per minute heart rate of 125 or more beats per minute previous COVID-19 treatments with mAbs Known allergies to any of the components used in the formulation of the trial drugs Hemodynamic instability requiring use of pressors within 24 hours of randomization Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that could potentially lead to hospitalization within 30 days Any co-morbidity requiring surgery within 7 days or that is considered life-threatening within 90 days History of positive SARS-CoV-2 test prior to 4 days of the eligibility assessment History of convalescent COVID-19 plasma treatment Participation in a clinical study involving an investigational intervention within the last 30 days Pregnancy or breast feeding Investigator site personnel directly affiliated with this study Sexually active women of childbearing potential or sexually active men who are unwilling to practice effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose Inability to participate to the study follow-up
Interventions
	Treatment Sotrovimab 500 mg of sotrovimab by intravenous infusion single dose Bamlanivimab+Etesevimab 700 mg of bamlanivimab + 1400 mg of etesevimab by intravenous infusion single dose
	Control REGN-COV2 600 mg of casirivimab + 600 mg of imdevimab by intravenous infusion single dose
Participants
	Randomized participants : REGN-COV2=106 Sotrovimab=107 Bamlanivimab+Etesevimab=106
	Characteristics of participants N= 319 Mean age : NR 170 males Severity : Mild: n= 311/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register COVID-19 progression [ Time Frame: 14 days ] (1) hospitalization or (2) need of supplemental oxygen therapy at home or (3) death within 14 days of randomisation
	In the report COVID-19 progression, defined as hospitalisation, need of supplemental oxygen therapy, or death from any cause through day 14.
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the pre-print article, the trial registry was used in data extraction and assessment of risk of bias. There is no change from the trial registration in the intervention and control treatments. The primary outcome in the article reflects that in the registry. Results are reported per variant of concerns (delta and omicron). Adverse events are not reported. The trial (n = 319) did not achieve its target sample size (n = 1260) as recruitment was interrupted after the publication of in-vitro evidence that two treatments under investigation (bamlanivimab/etesevimab and casirivimab/imdevimab) were not effective against the new emerging viral Omicron VOC. This study was updated on January 19th, 2023 with data extracted from the published report.