Covid-19 living Data

Lopinavir + Ritonavir vs Umifenovir (RCT)

Hospitalized patients

FOREST PLOTS -2021-06-18

Studies description

Trial IRCT20180725040596N2
Publication Nojomi M, BMC Infect Dis. (2020) (published paper)
Dates: 2020-04-20 to 2020-06-18
Funding: Public/non profit (Iran University of Medical Sciences)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Single center / Iran Follow-up duration (days): 30
Inclusion criteria	Non-pregnant women and men aged 18 years old or more with definite diagnosis of COVID-19 by RT-PCR or CT scan imaging (pneumonia), and oxygen saturation of 94% or less. The findings of CT were described as bilateral lung opacities and lobular and sub segmental areas of consolidation
Exclusion criteria	History of allergy to Arbidol class of drugs, abnormal liver or renal function, abnormal blood coagulation, Arbidol was used before inclusion, women who are nursing or pregnant, and patients with severe heart disease
Interventions
	Treatment HCQ+LPV/r Hydroxychloroquine: 400 mg on first day. Lopinavir/ritonavir: 400 mg twice a day for 7 to 14 days
	Control HCQ+Umif Hydroxychloroquine: 400 mg twice on first day Umifenovir: 200 mg orally 3 times a day for 7 to 14 days
Participants
	Randomized participants : HCQ+Umif=50 HCQ+LPV/r=50
	Characteristics of participants N= 100 Mean age : NR 60 males Severity : Mild: n=* / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register Fever, Complete blood count, C-reactive protein, chest CT Scan view symptoms, Measurement of blood oxygen saturation and no adjuvant oxygen therapy, Hospital admission days (NB - duration of hospitalisation was added as a primary outcome after study
	In the report Hospitalization duration and clinical improvement 7 days after 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	Some concerns
General comment	In addition to the pre-print article, the study registry was used in data extraction and risk of bias assessment. The target sample size specified in the registry was achieved. Several changes were made to the trial registration. Chest CT scan was added as an outcome during the conduct of the study. After study completion, changes were made to primary and secondary outcomes, including the addition of the primary outcome as reported in the pre-print article. During the conduct of the study the treatments in the trial registration were changed: the dosage of Umifenovir was increased; the duration of both study treatments was extended; the duration of Hydroxychloroquine treatment was extended in the Umifenovir arm but not in the Lopinavir-ritonavir arm.

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).