Covid-19 living Data

Mavrilimumab vs Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2021-04-01

Studies description

Trial NCT04399980, NCT04463004, NCT04492514
Publication MASH-COVID - Cremer P, Lancet Rheumatol (2021) (published paper)
Dates: 2020-05-28 to 2020-09-15
Funding: Private (Kiniksa Pharmaceuticals)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA Follow-up duration (days): 60
Inclusion criteria	Inpatient hospitalisation for COVID-19 documented COVID-19 pneumonia defined as a positive upper respiratory tract specimen for SARS-CoV-2 with associated abnormalities or infiltrates on chest x-ray or chest CT active fever or documented fever within 48 h or antipyretic use hypoxaemia, defined as a room air oxygen saturation of less than 92% or requirement of supplemental oxygen and a C-reactive protein concentration greater than 5 mg/dL.
Exclusion criteria	Age younger than 18 years absolute neutrophil count less than 1500/mm3 home oxygen therapy mechanical ventilation uncontrolled systemic bacterial infection and onset of symptoms more than 14 days before hospital admission and enrolment.
Interventions
	Treatment Mavrilimumab 6 mg/kg IV infusion once-off
	Control Placebo
Participants
	Randomized participants : Placebo=19 Mavrilimumab=21
	Characteristics of participants N= 40 Mean age : NR 26 males Severity : Mild: n=0 / Moderate: n=20 / Severe: n=20 Critical: n=0
Primary outcome
	In the register Proportion of subjects alive and off of oxygen at day 14 [ Time Frame: Day 14 ]
	In the report Proportion of patients alive and off supplemental oxygen therapy at day 14 after infusion of mavrilimumab or placebo
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
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 and statistical analysis plan were used in data extraction and assessment of risk of bias. There were no substantive differences between the published article and the protocol in population, procedures, interventions or outcomes. Exploratory outcomes included in the protocol were not included in the registry. Some exploratory outcomes that required laboratory testing were not fully measured due to pandemic demands on laboratory resources, and were therefore not reported. The study did not achieve its pre-stated sample size. Due to slow enrollment, the study was stopped early to inform the natural history and potential treatment effect.

Trial *
Publication Pupim L, Ann. Rheum. Dis (2021) (published paper)

Funding: Not reported/unclear
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA, Brazil, Chile, Peru, and South Africa Follow-up duration (days): 28
Inclusion criteria	Adults hospitalized with severe COVID-19 pneumonia and hyperinflammation requiring supplemental oxygen therapy without mechanical ventilation
Exclusion criteria	Patients requiring mechanical ventilation
Interventions
	Treatment Mavrilimumab 6 or 10 mg/kg intravenously once-off
	Control Placebo
Participants
	Randomized NR Analyzed 114 participants Mavrilimumab=75 Placebo=39
	Characteristics of participants N= 114 Mean age : NR 0 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register NR
	In the report Proportion of patients alive and free of mechanical ventilation at Day 29
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
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	*
General comment	The conference abstract was available for data extraction and risk of bias assessment. The trial is described as ongoing in the abstract. No registry, protocol or statistical analysis plan was available. The trial included patients with severe COVID-19 requiring supplemental oxygen and mechanical ventilation; only those not requiring mechanical ventilation are included in this report. Unclear whether the study achieved its sample size and unclear number of patients randomized and analyzed. No outcomes were extracted.