Covid-19 living Data

Interferon alpha2b vs Standard care (RCT)

Hospitalized patients

FOREST PLOTS -2022-03-04

Studies description

Trial CTRI/2020/12/029855
Publication Bhushan S, Int J Infect Dis (2021) (published paper)
Dates: 2020-12-16 to 2021-03-25
Funding: Private (Cadila Healthcare Ltd.)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / India Follow-up duration (days): 29
Inclusion criteria	Age ≥18 years RT-PCR confirmed SARS-CoV-2 infection pneumonia with no signs of severe disease respiratory rate (RR) ≥24 breaths/minute SpO2 90% to 94% for female patients of child-bearing potential, a negative pregnancy test. All subjects were hospitalized.
Exclusion criteria	ALT/AST >5 times the upper limit of normal. Stage 4 severe chronic kidney disease or required dialysis (i.e. eGFR <30) Pregnant or breast feeding Allergy to any study medication Severe co-morbidity (e.g. uncontrolled hypertension and uncontrolled DM, systemic disease which was affected the vital organs severity, immunocompromised patients etc.) as per investigator’s assessment Comorbid condition like myocardial infarction or heart failure within 90 days of recruitment Prolong QT interval (>450 ms).
Interventions
	Treatment Interferon alpha-2b 1 mcg/kg subcutaneously once-off
	Control Standard care
Participants
	Randomized participants : Interferon alpha-2b=120 Standard care=130
	Characteristics of participants N= 250 Mean age : NR 177 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=250 Critical: n=0
Primary outcome
	In the register Change in ordinal scale at Day 11 ± 1.
	In the report Change in ordinal scale at day 11 (two-point improvement in the WHO 7-point ordinal scale)
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 prospective trial registry and supplementary materials were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The study achieved its target sample size. There is no change from the trial registration in the intervention and control treatments. The primary outcome reported reflects that in the registry. SAE was an outcome in the registry; two deaths are reported in the safety outcomes section, but it is not clear whether these were the only SAEs. Other than that, the secondary outcomes reported reflect those in the registry. Four of five risk of bias domains were assessed to have some concerns. Commonly, this would be a reason to elevate the study overall to high risk of bias, but no individual outcome was some concerns in more than three domains.

Trial *
Publication Mordyk A, Infektsionnye Bolezni (2021) (published paper)

Funding: No specific funding
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Russia Follow-up duration (days): 22
Inclusion criteria	Presence of a clinically and laboratory confirmed diagnosis of "coronavirus infection COVID-19" (molecular genetic method - PCR and / or enzyme immunoassay (ELISA) mild, moderate forms of the disease treatment to the doctor no later than 48 hours from the moment of illness lack of therapy with drugs of the cytokine group and their inducers or other immunomodulatory drugs during the last two weeks before research the presence of a signed informed consent of the patient to participate in the study age from 18 to 65 years.
Exclusion criteria	Presence of hypersensitivity reactions a history of allergic reactions to interferon α-2b or its components, or an established allergic reaction at the time of first administration of study drug suspicion of the initial manifestations of a disease similar to COVID-19 symptoms (other infectious diseases, influenza-like syndrome at the onset of systemic diseases of the connective tissue, oncological, hematological and other pathologies) presence of concomitant disease the need for treatment which may affect the evaluation of the results of the study (atopic moderate to severe dermatitis, chronic diseases of the liver and kidneys, pronounced dysfunction of the thyroid gland and other diseases of the endocrine system (decompensated diabetes mellitus) severe diseases of the system hematopoiesis, epilepsy and other diseases of the central nervous system) other diseases which will not allow the patient to participate in research age under 18 and over 65 years old severe form of the disease the patient's unwillingness to strictly follow the doctor's prescription the use of group drugs cytokines and their inducers or other immunomodulatory drugs during the last two weeks before the start of the study and the need for their use during the study period taking other medications drugs that, according to investigator, may affect the course and the results of the clinical trial the presence of HIV infection, syphilis, hepatitis B, C with severe clinical and laboratory activity participation in another clinical study simultaneously or three months before the start of this one other heavy decompensated or unstable somatic diseases that threaten the patient's life or worsen the patient's prognosis, and also make it impossible to participation in a clinical trial pregnancy or breastfeeding period other conditions which, in the opinion researcher prevent the patient from being included in the study.
Interventions
	Treatment Interferon alpha-2b 3,000,000 IU rectally 3 times a day for 14 days; 4000 IU topically (nasal mucosa and palatine tonsils) 5 times a day for 14 days
	Control Standard care
Participants
	Randomized participants : Interferon alpha-2b=70 Standard care=70
	Characteristics of participants N= 140 Mean age : NR 70 males Severity : Mild: n=* / Moderate: n=* / Severe: n=0 Critical: n=0
Primary outcome
	In the register NR
	In the report NR
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	Only the published article was used in data extraction and risk of bias assessment. The abstract was available in English while the full paper was translated from Russian using Google translate. Neither the protocol, statistical analysis plan or registry were available and therefore we cannot determine if the intervention and outcomes were determined a priori.

Trial CTRI/2020/06/026087
Publication Pandit A, Int J Infect Dis (2021) (published paper)
Dates: 2020-07-08 to 2020-09-04
Funding: Private (Cadila Healthcare Limited)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / India Follow-up duration (days): 29
Inclusion criteria	Age ≥18 years RT-PCR confirmed SARSCoV-2 infection pneumonia with no signs of severe disease respiratory rate 15–30 breaths/min SpO2 90%–94% for female patients of child-bearing potential, a negative pregnancy test prior to treatment C-reactive protein (CRP) < 16 mg/L IL-6 < 100 pg/mL D-dimer < 2 mg/mL interferon-g, ferritin, tumor necrosis factor (TNF)-α, IL-1β greater than an upper limit of normal (ULN) illness of any duration and radiographic infiltrates by chest X-ray or evidence of rales/crackles or other clinical symptoms on clinical examination.
Exclusion criteria	Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 x ULN stage 4 severe chronic kidney disease or required dialysis (i.e., estimated glomerular filtration rate <30 mL/min/1.73 m2) pregnant or breast-feeding women severe co-morbidity (e.g., uncontrolled hypertension, uncontrolled diabetes mellitus, systemic disease which had affected the vital organs severely, immunocompromised patients, etc.) comorbid condition like myocardial infarction or heart failure within 90 days of recruitment prolonged QT interval (>450 ms).
Interventions
	Treatment Interferon alpha-2b 1 mcg/kg subcutaneous injection, single dose
	Control Standard care
Participants
	Randomized participants : Interferon alpha-2b=20 Standard care=20
	Characteristics of participants N= 40 Mean age : NR 30 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register Evaluation of the clinical efficacy of Pegylated IFN-?2b on the basis of change in ordinal scale
	In the report Clinical status assessed on day 15 on a WHO 7-point ordinal scale consisting of the following categories: 1, not hospitalized, no limitations of activities; 2, not hospitalized, limitation on activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, on non-invasive ventilation or high flow oxygen devices; 6, hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 7, death
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 study registry was used in data extraction and risk of bias assessment. No study protocol or statistical analysis plan was available. The study achieved its prespecified target sample size. Some secondary outcomes were not pre-specified including occurrence and duration of supplemental oxygen and mechanical ventilation, duration of hospitalization, change from baseline in white blood cell count (WBC), hemoglobin (Hb), platelets, creatinine, glucose, total bilirubin, ALT and AST, and change from baseline in CRP, IL-6, D-dimer, interferon-g, ferritin, TNF-α, and IL-1β until Day 14. The primary outcome (i.e., clinical improvement) was only reported at one of two pre-specified timepoints (i.e., reported at day 15 but not day 30). The published article specifies administration of a single dose of the intervention which differs from the two doses (day 1 and day 8) specified in the registry.