Covid-19 living Data

Umifenovir vs Standard care (RCT)

Hospitalized patients

FOREST PLOTS -2022-01-21

Studies description

Trial CTRI/2020/09/027535
Publication Ramachandran R, Int. J. Infect. Dis. (2021) (published paper)
Dates: 2020-10-03 to 2021-04-28
Funding: Public/non profit (Council of Scientific and Industrial Research, Ministry of Science and Technology, Government of India)
Conflict of interest: No

Methods
	RCT Blinding: double blinding
	Location : Multicenter / India Follow-up duration (days): 28
Inclusion criteria	Aged 18-75 years, at the time of signing the Informed Consent Form (ICF) Nasopharyngeal swab positivity in RT-PCR tests for SARS-Cov-2 antigens Asymptomatic or mild (uncomplicated upper respiratory tract viral infection and who may have non-specific symptoms such as fever, cough, expectoration, shortness of breath, myalgia, fatigue, sore throat, nasal congestion, diarrhea, loss of taste) or moderate (Pneumonia with no signs of severe disease, including adults with presence of clinical features of dyspnea and or hypoxia, fever, cough, including SpO2 <94% (range 90-94%) on room air, respiratory rate more or equal to 24 per minute) disease
Exclusion criteria	Severe covid with respiratory rate >30 breaths/min, severe respiratory distress, SpO2 <90% on room air Acute respiratory distress syndrome (ARDS) Sepsis/ septic shock Pregnant/ lactating women Severe lever disease, severe renal impairment, or other comorbidities like asthma, diabetes with second and third line medicines as defined in the WHO guidance document
Interventions
	Treatment Umifenovir 800 mg orally twice daily for 14 days
	Control Standard care
Participants
	Randomized participants : Umifenovir=66 Standard care=66
	Characteristics of participants N= 132 Mean age : NR 92 males Severity : Mild: n=* / Moderate: n=41 / Severe: n=0 Critical: n=0
Primary outcome
	In the register Time from randomization to nasopharyngeal swab negativity by RT-PCR tests; For moderate patients: time to improvement by one category from randomisation on the eight-category ordinal scale defined by WHO & average change in the ordinal scale from baseline
	In the report Mild-asymptomatic patients: Time from randomization to nasopharyngeal swab negativity by two RT-PCR tests, for SARS-Cov-2 antigens, taken 24 hours apart; Moderate patients: time to improvement by one category from randomisation on the eight-category ordinal scale defined by WHO & average change in the ordinal scale from baseline
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: N
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 and protocol were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The registry primary outcomes reflect the reported primary outcomes. Some outcomes (e.g. mortality) are reported in the paper, but was not pre-specified in the trial registry/protocol. Participants were stratified at randomization and analyzed by severity at baseline (asymptomatic + mild or moderate severity).

Trial *
Publication Yethindra V, Int J Res Pharm Sci (2020) (published paper)
Dates: 2020-03-12 to 2020-05-11
Funding: No specific funding (Not applicable)
Conflict of interest: No

Trial NCT04252885
Publication Yueping L, CellPress (2020) (published paper)
Dates: 01feb2020 to 28mar2020
Funding: Public/non profit (Project 2018ZX10302103-002, 2017ZX10202102-003-004 and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021) )
Conflict of interest: No

Methods
	RCT Blinding: Participants
	Location : Single center / China Follow-up duration (days): 21
Inclusion criteria	1) Age between 18 and 80 years old 2) SARS-CoV-2 infection confirmed by real-time PCR (RT-PCR) from pharyngeal swab 3) Mild clinical status, defined as having mild clinical symptoms but no signs of pneumonia on imaging or moderate clinical status, defined as having fever, respiratory symptoms and pneumonia on imaging 4) The following lab findings: creatinine ?110?mol/L, creatinine clearance rate (eGFR) ?60 ml/min/1.73m2, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?5 × ULN, and total bilirubin (TBIL) ?2 × ULN 5) willing to participate the study and sign the informed consent
Exclusion criteria	1) Known or suspected to be allergic to LPV/r or Umifenovir 2) Having severe nausea, vomiting, diarrhea or other complaints affecting oral intake or absorption in the digestive tract 3) Taking other drugs that may interact with LPV/r or Umifenovir 4) Having serious underlying diseases, including but not limited to heart, lung, or kidney disease, liver malfunction, or mental diseases affecting treatment compliance 5) Complicating with pancreatitis or hemophilia prior to the trial 6) Pregnant or lactating women 7) Having the suspected or confirmed history of alcohol or substance use disorder 8) Having participated in other drug trials in the past month 9) Deemed otherwise unsuitable for the study by the researchers.
Interventions
	Treatment Lopinavir-Ritonavir LPV/r: 200/50 mg orally twice a day for 7-14 days Umifenovir 200 mg orally 3 times a day for 7-14 days
	Control Standard care
Participants
	Randomized participants : Lopinavir-Ritonavir=34 Umifenovir=35 Standard care=17
	Characteristics of participants N= 86 Mean age : NR 40 males Severity : Mild: n=11 / Moderate: n=75 / Severe: n=0 Critical: n=0
Primary outcome
	In the register The rate of virus inhibition [ Time Frame: Day 0, 2, 4, 7, 10, 14 and 21 ]
	In the report Time of positive-to-negative conversion of SARS-CoV-2 nucleic acid from initiating treatment to day 21, with the enrollment day as the first day of treatment
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: No
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 all available versions of the published/pre-print article, the study registry and the reply provided by authors were used in data extraction and risk of bias assessment.The study did not achieve the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The primary outcome indicated in the registry is measured at multiple time points, some of which are not reported in the paper. Some outcomes are reported in the paper, but were not pre-specified in the trial registry/protocol (e.g., adverse events).

Methods
	RCT
	Location : Single center / Kyrgyzstan Follow-up duration (days): 21
Inclusion criteria	1) age 18–60 years 2) SARS-CoV-2 infection confirmed by rRT-PCR from naso and oropharyngeal swabs 3) mild clinical status (mild clinical symptoms but no signs of pneumonia with CT scanning) and moderate clinical status (symptoms like pyrexia, respiratory symptoms, and pneumonia upon CT scanning) 4) body temperature > 37◦C and oxygen saturation (SaO2) > 93% and 5) acceptance for recruitment in the study and providing written consent.
Exclusion criteria	1)severe/critical illness 2) allergies to umifenovir 3) exhibiting severe side effects, such as nausea, vomiting, diarrhea, or other gastrointestinal symptoms 4) receiving other drugs that may interact with umifenovir 5) pregnant or lactating women 6) cardiac, liver, or renal disease 7) gestation or lactation and 8)enrollment in different drug trials within the previous 30 days.
Interventions
	Treatment Umifenovir 200 mg orally 3 times a day for 1-5 days
	Control Standard care
Participants
	Randomized participants : Umifenovir=15 Standard care=15
	Characteristics of participants N= 30 Mean age : NR 18 males Severity : Mild: n=* / Moderate: n=* / Severe: n=0 Critical: n=0
Primary outcome
	In the register NR
	In the report Time to clinical recovery (TTCR), a composite of body temperature and cough amelioration over 72 h.
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 assessment of risk of bias. No trial registry, protocol or statistical analysis plan was available. Limited data to assess RoB (no information on blinding of the participants/carers/outcome assessors), and insufficient data on baseline characteristics of 30 participants included in the study.