Covid-19 Living Data

Trial NCT04501978
Publication ACTIV-3/TICO Study Group, Ann Intern Med (2022) (published paper)
Dates: 2021-06-11 to 2021-11-15
Funding: Mixed (U.S. Operation Warp Speed program; the National Institute of Allergy and Infectious Diseases and Leidos Biomedical Research for the INSIGHT Network; the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the Prevention and Early Treatment of Acute Lung Injury Network and the Cardiothoracic Surgical Trials Network; the U.S. Department of Veterans Affairs; the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), the United Kingdom (Medical Research Council), and Singapore (National Medical Research Council); National Institutes of Health and National Cancer Institute. Trial medications were donated by Molecular Partners (ensovibep) and Gilead Sciences (remdesivir). The funding organizations had no direct involvement in the decisions related to the trial or the drafting or revision of the manuscript.)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / USA, Greece, Uganda, Singapore, UK, Nigeria, Denmark, Switzerland, Poland, and Spain. Follow-up duration (days): 90
Inclusion criteria	Hospitalized (NOT for purely public health or quarantine purposes) Aged ≥18 years Had SARS-CoV-2 infection documented by a nucleic acid amplification test or equivalent COVID-19 symptoms had been present for at most 12 days at the time of randomization Informed consent by the patient or the patient’s legally authorized representative Vaccination against SARS-CoV-2 was not exclusionary
Exclusion criteria	Requiring any of the following interventions at baseline: invasive mechanical ventilation, extracorporeal membrane oxygenation or other forms of mechanical circulatory support, vasopressor therapy, or commencement of renal replacement therapy during admission 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 (with the approval of study leadership, enrollment before or on Day 5 is permitted for trials comparing different approaches for implementing SOC interventions that are recommended in Appendix I) 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 acknowledge the strong advice to abstain from sexual intercourse with men or practice appropriate contraception through 18 months of the study Men who are unwilling to acknowledge the strong advice to abstain from sexual intercourse with women of child-bearing potential or to use barrier contraception through 18 months of the study.
Interventions
	Treatment Ensovibep 600 mg IV infusion single dose
	Control Placebo
Participants
	Randomized participants : Placebo=241 Ensovibep=255
	Characteristics of participants N= 496 Mean age : NR 275 males Severity : Mild: n=95 / Moderate: n=292 / Severe: n=98 Critical: n=0 Number of vaccinated participants: 62
Primary outcome
	In the register 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 sustained clinical recovery up to day 90, defined as the time from randomization to return to home (the participant's residence or a facility that provided the same or a less intensive level of clinical care before COVID-19) for 14 consecutive days
Documents available	Protocol Yes. In English Statistical plan Yes 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 published article and its supplement, the study protocol, SAP and registry were used in data extraction and risk of bias assessment. On 15 November 2021, the DSMB recommended stopping the study for futility, so the study did not achieve the target sample size of 1000. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome.