Covid-19 Living Data

Trial ChiCTR2000029308
Publication Cao B, N Engl J Med (2020) (published paper)
Dates: 18jan2020 to 03feb2020
Funding: Mixed (Major Projects of National Science and Technology on New Drug Creation and Development; Chinese Academyof Medical Sciences (CAMS) Emergency Project of Covid-19; National Science Grant for DistinguishedYoung Scholars.
Dr. Jaki is a recipient of)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Single center / China Follow-up duration (days): 28
Inclusion criteria	Male and nonpregnant female patients 18 years of age or older were eligible if they had a diagnostic specimen that was positive on RT-PCR, had pneumonia confirmed by chest imaging, and had an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) (Pao2:Fio2) at or below 300 mg Hg.
Exclusion criteria	Physician decision that involvement in the trial was not in the patient’s best interest, presence of any condition that would not allow the protocol to be followed safely, known allergy or hypersensitivity to lopinavir–ritonavir, known severe liver disease (e.g., cirrhosis, with an alanine aminotransferase level >5× the upper limit of the normal range or an aspartate aminotransferase level >5× the upper limit of the normal range), use of medications that are contraindicated with lopinavir–ritonavir and that could not be replaced or stopped during the trial period (see the Supplementary Appendix, available with the full text of this article at NEJM.org) pregnancy or breast-feeding, or known HIV infection, because of concerns about the development of resistance to lopinavir–ritonavir if used without combining with other antiretrovirals.
Interventions
	Treatment Lopinavir-Ritonavir LPV/r: 400mg and 100mg orally twice a day for 14 days.
	Control Standard care
Participants
	Randomized participants : Lopinavir-Ritonavir=99 Standard care=100
	Characteristics of participants N= 199 Mean age : NR 120 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=199 Critical: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Clinical improvement time of 28 days after randomization; The 7-point scale; 7 points: death; 6 points: admission to ECMO and / or mechanical ventilation; 5 points: Hospitalized for non-invasive ventilation and / or high-flow oxygen therapy 4 points: hospitalization for oxygen therapy 3 points: Hospitalization does not require oxygen therapy 2 points: discharged but not restored to normal functional status 1 point: discharged to normal function
	In the report Time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first
Documents available	Protocol Yes. In language other than English 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 all available versions of the published/pre-print article, the study registry and protocol were used in data extraction and risk of bias assessment. The protocol, which was available only in Chinese, was examined by native speakers. 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 primary outcome indicated in registry reflects the primary outcome reported in the paper. Some outcomes from the registry are not reported in the paper (e.g., proportion of patients in each category of the 7-point scale on day 28 after randomization).