Covid-19 Living Data

Trial NCT04501978
Publication Lundgren J, medRxiv, 2021 (preprint)
Dates: 2020-08-05 to 2020-10-13
Funding: Mixed (U.S. Operation Warp Speed; National Institute of Allergy & Infectious Diseases; Leidos Biomedical Research; National Heart, Lung & Blood Institute; Research Triangle Institute; U.S. Dept of Veterans Affairs; Denmark, Aus)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Denmark, Singapore, USA Follow-up duration (days): 90
Inclusion criteria	Age ≥ 18 years; Informed consent by the patient or the patient’s legally-authorized representative ; SARS-CoV-2 infection, documented by PCR or other nucleic acid test (NAT) within 3 days prior to randomization OR documented by NAT more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator; Duration of symptoms attributable to COVID-19 ≤ 12 days per the responsible investigator; Requiring admission for inpatient hospital acute medical care for clinical manifestations of COVID-19, per the responsible investigator, and NOT for purely public health or quarantine purposes.
Exclusion criteria	Prior receipt of Any SARS-CoV-2 hIVIG, convalescent plasma from a person who recovered from COVID-19 or SARS-CoV-2 nMAb at any time prior to hospitalization; Not willing to abstain from participation in other COVID-19 treatment trials until after Day 5; In the opinion of the responsible investigator, any condition for which, participation would not be in the best interest of the participant or that could limit protocol-specified assessments; Expected inability to participate in study procedures; Women of child-bearing potential who are not already pregnant at study entry and who are unwilling to abstain from sexual intercourse with men or practice appropriate contraception through Day 90 of the study. Men who are unwilling to abstain from sexual intercourse with women of child-bearing potential or who are unwilling to use barrier contraception through Day 90 of the study. Presence at enrollment of any of the following: a. stroke b. meningitis c. encephalitis d. myelitis e. myocardial infarction f. myocarditis g. pericarditis h. symptomatic congestive heart failure (NYHA class III-IV) i. arterial or deep venous thrombosis or pulmonary embolism
Interventions
	Treatment Bamlanivimab (LY-CoV555) 7000 mg IV infusion once-off
	Control Placebo Duration : 1 hour
Participants
	Randomized 326 participants (n₁=169 / n₂= 157)
	Characteristics of participants N=326 Mean age : NR 177 males Severity : Mild: n=86 / Moderate: n=/ Severe: n= Critical: n=0
Primary outcome
	In the register Pulmonary ordinal outcome [ Time Frame: Day 5 ] Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used ; Pulmonary+ ordinal outcome [ Time Frame: Day 5 ] Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used. Time from randomization to sustained recovery [Time Frame: Up to Day 90 ] Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
	In the report Time to a sustained recovery, which was defined as hospital discharge to home and remaining at home for at least 14 days. Two ordinal outcomes that are measured at day 5 both classified according to seven-level ordinal scales, are termed pulmonary
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing stated 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 published article, the trial registry, study protocol, statistical analysis plan and supplementary materials were used in data extraction and assessment of risk of bias. There were no substantive differences between the published article and the trial registry, study protocol and statistical analysis plan. The trial did not achieve its pre-stated sample size as it was terminated for futility on the recommendation of the data and safety monitoring board. Quote: "In order to respond to pandemic dynamics, this platform protocol incorporates an early futility and safety evaluation after the enrollment of 300 patients (stage 1). Stage 1 is then followed by enrollment to the full sample size (stage 2) for agents that pass the initial futility and safety assessment." "The analysis data set was locked on November 6, 2020, and includes deaths, serious adverse events, organfailure events, and hospital discharges that occurred up to October 26." Chance imbalances in illness severity at baseline were detected and reported by the authors, but adjusted analyses did not suggest benefit for LY-CoV555 in this patient population. This trial was updated on July 29th, 2021 with data from a preprint article reporting final results.