Covid-19 Living Data

Trial NCT04373460
Publication Sullivan D, N Engl J Med (2022) (published paper)
Dates: 2020-06-03 to 2021-10-01
Funding: Mixed (U.S. Department of Defenses (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency (DHA); Bloomberg Philanthropies; State of Maryland; the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases; NIH National Center for Advancing Translational Sciences; Division of Intramural Research NIAID NIH; Mental Wellness Foundation; Moriah Fund; Octapharma; HealthNetwork Foundation; the Shear Family Foundation.)
Conflict of interest: No

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA Follow-up duration (days): 28
Inclusion criteria	≥ 18 years of age Competent and capable to provide informed consent Positive molecular test for presence of SARS-CoV-2 in fluid collected by saliva for antigen, oropharyngeal or nasopharyngeal swab Experiencing any symptoms of COVID-19 including but not limited to fever(T> 100.5º F), cough, or other COVID associated symptoms like anosmia ≤ 8 days since the first symptoms of COVID-19 ≤ 8 days since first positive SARS-CoV-2 RNA test Able and willing to comply with protocol requirements listed in the informed consent
Exclusion criteria	Hospitalized or expected to be hospitalized within 24 hours of enrollment Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance History of prior reactions to transfusion blood products Inability to complete therapy with the study product within 24 hours after enrollment Receiving any treatment drug for COVID-19 within 14 days prior to screening evaluation (monoclonal antibodies, compassionate use or study trial related). Steroid treatment at any time does not affect study eligibility
Interventions
	Treatment Convalescent plasma 250 mL intravenously over 1 hour once-off
	Control Placebo
Participants
	Randomized participants : Convalescent plasma=610 Placebo=615
	Characteristics of participants N= 1225 Mean age : NR 506 males Severity : Mild: n= 1181/ Asymptomatic: n=0 Number of vaccinated participants: 72
Primary outcome
	In the register 1. Cumulative incidence of hospitalization or death prior to hospitalization [ Time Frame: Up to day 28 ]; 2. Cumulative incidence of treatment-related serious adverse events [ Time Frame: Up to day 28 ]; 3. Cumulative incidence of treatment-related grade 3 or higher adverse events [ Time Frame: Up to day 90 ]
	In the report Covid-19–related hospitalization within 28 days after transfusion, assessed as the cumulative incidence in the convalescent- plasma group as compared with the control-plasma group. Although death before hospitalization was part of the protocol-specified primary outcome, it did not occur in the trial. Hence, the primary outcome is equivalent to Covid-19–related hospitalization.
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	Low
General comment	In addition to the pre-print article, data from contact with authors and the study registry was used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plane was available. Recruitment to the trial (n = 1225) was terminated due to declining hospitalizations among enrolled participants and thus did not achieve its target sample size (n = 1344).The registry states that at least 175 mL of convalescent plasma would be administered and the pre-print indicates that approximately 250 mL was delivered. One primary outcome in the registry was death prior to hospitalization or hospitalization; as no deaths occurred prior to hospitalization, this outcome is reported as hospitalization. Two other primary safety outcomes are not defined as primary in the article, but are reported. Secondary outcomes reported in the registry are not reported in the pre-print (e.g., change in serum SARS-CoV-2 antibody titers, Time to SARS-CoV-2 Polymerase Chain Reaction (PCR) negativity). The outcomes "hospitalization or death" and "WHO Score 7 and above" were extracted through day 28. Extraction and risk of bias assessments were updated on 28 March 2022 after contact with the study author.