Covid-19 Living Data

Trial NCT04363736
Publication MARIPOSA - Kumar PN, Open Forum Infect Dis (2021) (published paper)

Funding: Private (F. Hoffmann-La Roche Ltd.)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / USA Follow-up duration (days): 60
Inclusion criteria	≥18 years old hospitalized moderate to severe COVID-19 pneumonia detected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive reverse-transcription polymerase chain reaction (RT-PCR) (within 7 days before randomization) and confirmed by chest radiography or computed tomography scan. Severe COVID-19 pneumonia was defined as patients having blood oxygen saturation of ≤93% or partial pressure of oxygen to fraction of inspired oxygen ratio of <300 mm Hg. Patients with moderate pneumonia did not meet the oxygen requirements of severe pneumonia but had evidence of inflammation as indicated by CRP levels >2× the upper limit of normal (ULN).
Exclusion criteria	On invasive ventilation >24 hours on ECMO in shock with multiorgan failure requiring treatment in an intensive care unit.
Interventions
	Treatment Tocilizumab 4 mg/kg 4 mg/kg (maximum 800 mg) intravenously once off. Second similar dose within 8-24 hours if sustained fever or clinical worsening.
	Control Tocilizumab 8 mg/kg 8 mg/kg (maximum 800 mg) intravenously once-off. Second similar dose within 8-24 hours if sustained fever or clinical worsening.
Participants
	Randomized participants : Tocilizumab 4 mg/kg=50 Tocilizumab 8 mg/kg=50
	Characteristics of participants N= 100 Mean age : NR 57 males Severity : Mild: n=14 / Moderate: n=27 / Severe: n=44 Critical: n=12 Number of vaccinated participants: NR
Primary outcome
	In the register 1)Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab); [ Time Frame: Days 0-28. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms. ] 2)Maximum Serum Concentration (Cmax) of Tocilizumab [ Time Frame: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms. ]; 3)Clearance (CL) of Tocilizumab [ Time Frame: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms. ]; 4)Volume of the Central Compartment (Vc) of Tocilizumab [ Time Frame: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms. ]; 5) Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ [ Time Frame: Baseline - Day 60 ]; 6) Serum Concentration of Ferritin Following Administration of IV TCZ [ Time Frame: Baseline - Day 60 ]; 7) Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ [ Time Frame: Baseline - Day 60 ]; 8) Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ [ Time Frame: Baseline - Day 60 ]
	In the report Serum concentrations of 1) tocilizumab and soluble interleukin 6 receptor (sIL-6R), 2) IL-6, 3) ferritin, and 4) C-reactive protein (CRP), from baseline to day 60.
Documents available	Protocol Yes. In English Statistical plan Yes 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 trial registry, protocol, statistical analysis plan, supplementary appendices and data from contact with authors were used in data extraction and assessment of risk of bias. The registry included seven primary outcomes; no outcomes are defines as primary in the article, but the reported outcomes reflect those in the registry. The trial (n = 100) achieved its target sample size (n = 100). This study was updated on April 27th, 2022 with data acquired after contact with authors.