Trial NCT04397562
Publication Lomakin N V, Inflamm Res, 2021 (published paper)
Dates: 2020-04-29 to 2020-08-03
Funding: Private (JSC BIOCAD)
Conflict of interest: Yes
Methods | |
RCT Blinding: double blinding | |
Location :
Multicenter / Russian Federation Follow-up duration (days): 60 | |
Inclusion criteria | Men and non-pregnant women aged 18 years or older; positive for SARS-CoV-2 RNA; hospitalized with radiologically confirmed pneumonia with at least one criteria of disease severity (respiratory rate >30/min, SpO2 ≤93%, PaO2/FiO2 ≤300 mmHg, increase of the lung involvement by more than 50% after 24–48 h, decreased consciousness level, agitation, unstable hemodynamics, arterial blood lactate >2 mmol/L, quick sequential organ failure assessment score (qSOFA) >2, defined by the presence of any two symptoms of the following: systolic blood pressure ≤100 mm Hg, respiratory rate ≥22/min, Glasgow Coma Scale score ≤14) |
Exclusion criteria | Critical form of COVID-19 (defined by the presence of any of the following: respiratory failure and need of the invasive mechanical ventilation, septic shock, multiple organ failure); suspected active bacterial, fungal, viral, or other infection (besides COVID-19); confirmed active tuberculosis; life expectancy <24 h, in the opinion of the investigator or who were unlikely to remain at the investigational site beyond 48 h; treated with other monoclonal antibodies, immunosuppressive agents or participating in a clinical trials of other drug; history of allergic reaction to monoclonal antibodies; any illness or laboratory fndings that, in the opinion of the study investigator, might pose an additional risk to the patient by their participation in the study; pregnant or breastfeeding women; ALT and/or AST levels >10×ULN; platelet count <50× 10^9/L; absolute neutrophil count <1.0× 10^9/L |
Interventions | |
Treatment
Placebo * |
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Control
Levilimab ( / ) | |
Participants | |
Randomized 206 participants (n1=103 / n2= 103) | |
Characteristics of participants N=206 Mean age : 58.4 109 males Severity : Mild: n=* / Moderate: n=*/ Severe: n=3 Critical: n=0 | |
Primary outcome | |
In the register Proportion of patients with sustained clinical recovery [ Time Frame: Day 14 ]: Sustained clinical recovery is defined as either an improvement of at least 2 categories relative to baseline on a 7-Category Ordinal Scale of Clinical Status or reaching categories "Discharged" / "Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care" at day 14 | |
In the report Overall mortality initial), ≥2-category improvement in clinical status relative to baseline on the 7-category ordinal scale or reaching the clinical status of categories 1 or 2 on Day 14 (amended) | |
Documents available |
Protocol NR Statistical plan NR Data-sharing stated
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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 retrospective study registry was used in data extraction and risk of bias assessment. The protocol and analysis plan were not available. The trial had an adaptive design with the pre-planned opportunity to modify the endpoints, intervention doses, sample size, or the size of the study groups. Changes were made to the primary outcome, switching from mortality to clinical improvement because the study did not have enough power to detect the difference between the groups using overall mortality. In addition, there is a minor change from the trial registration in the intervention and control treatments (same dosage, but delivered in two doses vs a single dose). Of note: The protocol allowed open label rescue administration of the intervention drug (ocurred in 13 participants in the intervention group and in 42 participants in the placebo group). |