Covid-19 living Data

Tocilizumab vs Dexamethasone (RCT)

Hospitalized patients

FOREST PLOTS -2022-02-17

Studies description

Trial CTRI/2021/04/033263
Publication Naik NB, Cureus (2021) (published paper)
Dates: 2021-05-06 to 2021-06-30
Funding: Public/non profit (Source of monetary of material support - Post Graduate Institute of Medical Education and Research)
Conflict of interest: *

Methods
	RCT Blinding: Unblinded
	Location : Single center / India Follow-up duration (days): 28
Inclusion criteria	18 years and older confirmed SARS-CoV-2 infection by reverse-transcriptase polymerase chain reaction (RT-PCR) assay partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio of less than 200 on admission and receiving standard care clinical worsening in less than 48 hours of the initiation of standard care (Clinical worsening was defined as follows: (1) decrease in PaO2/FiO2 by more than 50 of the baseline admission value, (2) oxygenation/ventilation device is upgraded, and (3) static or rising levels of C-reactive protein (CRP > 50 mg/L))
Exclusion criteria	prior history of immunosuppression and use of immunosuppressive drugs, raised septic biomarkers suggestive of invasive bacterial or fungal infection, AST/ALT ≥ five times the upper limit of normal, leukocytes < 2 × 103/μL, thrombocytes < 50 × 103/μL, and acute or chronic diverticulitis
Interventions
	Treatment Tocilizumab 6 mg/kg intravenously once-off. An additional similar dose after 24 hours if no clinical improvement.
	Control Dexamethasone 20 mg intravenously once daily for 3 days
Participants
	Randomized participants : Dexamethasone=21 Tocilizumab=21
	Characteristics of participants N= 42 Mean age : NR 24 males Severity : Mild: n=0 / Moderate: n=36 / Severe: n=6 Critical: n=0
Primary outcome
	In the register Ventilator free days (VFD) Timepoint: 0-28days following admission.
	In the report Ventilator-free days (VFDs) within 28 days since randomization.
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	Some concerns
General comment	In addition to the published article, the trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. Only graphical summaries of the protocol and statistical analysis plan were available. The study was terminated at the interim analysis stage due to increased mortality and adverse event rate observed in the high dose dexamethasone arm and therefore did not achieve the target sample size (n=42 of planned n=102). The primary outcome indicated in registry reflects the primary outcome reported in the paper. There is no change from the trial registration in the intervention and control treatments.

Trial NCT04519385
Publication Rashad A, Scientific Reports (2021) (published paper)
Dates: 2020-03-01 to 2020-06-30
Funding: Not reported/unclear (Open access funding: Qatar National Library)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Single center / Egypt Follow-up duration (days): 14
Inclusion criteria	Significant deterioration in respiratory clinical status with respiratory rate > 30 cycle/minute Bilateral Chest computed tomography (CT) infiltration > 30% PaO2/FiO2 ratio < 150 or saturation < 90 on > 6 L/min Two positive laboratory tests of the following: (CRP > 10 g/L, lymphocytes < 600 /mm3, D-dimer > 500 ng/mL , ferritin > 500 ng/mL)
Exclusion criteria	Pediatric patients < 18 years old active bacterial or fungal infection patients on chemotherapy patients with interstitial lung disease patients who were not requiring supplemental oxygen
Interventions
	Treatment Tocilizumab 4 mg/kg IV once daily for two days
	Control Dexamethasone Initial dose: 4 mg/kg IV once daily for 3 days, Maintenance dose: 8 mg once daily for ten days
Participants
	Randomized participants : Tocilizumab=74 Dexamethasone=75
	Characteristics of participants N= 149 Mean age : NR 62 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=70 Critical: n=39
Primary outcome
	In the register Proportion of participants with Overall Survival at 14 days
	In the report Time to failure, defined as death, within 14 days from ICU admission
Documents avalaible	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	High
General comment	In addition to the published article, the retrospective study registry was used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan was available. Blinding is unclear: the report states that “Patients, investigators, and health-care providers were not masked to study drug assignment”; despite being retrospectively registered, the trial is described as single-blind in the registry, with participants and outcome assessor blinded. Described in the report as taking place “in the ICU of ESNA hospital, the first COVID-19 quarantine hospital in Egypt”; yet randomization described as being “stratified by site”. The secondary outcome included in the registry (Fio2/Pao2, Time Frame: 2 days) is not reported as an outcome, but rather considered as a predictor for survival. The study excluded all deaths within the first 3 days (38% vs. 16% of participants in the two groups) from mortality analyses and was consequently assessed as high risk of bias.