NCT04546581.

Study name	Inpatient treatment with anti‐coronavirus immunoglobulin (ITAC)
Methods	Trial design:  International multicentre, adaptive, randomised, double‐blind, placebo‐controlled trial Sample size: 593 Setting: inpatient Countries: Denmark, Greece, Japan, Nigeria, Spain, United Kingdom, United States Language: English Number of centres: 39
Participants	Inclusion criteria 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 Symptomatic COVID‐19 disease Duration of symptoms attributable to COVID‐19 ≤ 12 days Requiring inpatient hospital medical care for clinical manifestations of COVID‐19 (admission for public health or quarantine only is not included) Willingness to abstain from participation in other COVID‐19 treatment trials until after study Day 7 Provision of informed consent by participant or legally authorised representative Exclusion criteria Prior receipt of SARS‐CoV‐2 hIVIG or convalescent plasma from a person who recovered from COVID‐19 at any time Prior receipt of standard IVIG (not hyperimmune to SARS‐CoV‐2) within 45 days Current or predicted imminent (within 24 hours) requirement for any of the following: Invasive ventilation Non‐invasive ventilation Extracorporeal membrane oxygenation Mechanical circulatory support Continuous vasopressor therapy History of allergy to IVIG or plasma products History of selective IgA deficiency with documented presence of anti‐IgA antibodies Any medical conditions for which receipt of the required volume of intravenous fluid may be dangerous to the patient (includes New York Association Class III or IV stage heart failure) Any of the following thrombotic or procoagulant disorders: Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous thrombosis within 28 days of randomisation History of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol‐specified assessments
Interventions	Details of hyperimmune immunoglobulin therapy: drug name: Hyperimmune immunoglobulin to SARS‐CoV‐2 (hIVIG) dose: 100mg/ml number of doses: 1 route: iIntravenous use source: human Treatment details, including time of plasma therapy (e.g. early stage of disease): For studies including a control group: comparator (type): placebo (saline infusion) Concomitant therapy: Remdesivir Treatment cross‐overs: none
Outcomes	Primary study outcome:  clinical status on ordinal scale (day 7) 7. Death 6. End‐organ failure 5. Life‐threatening end‐organ dysfunction 4. Serious end‐organ dysfunction 3. Moderate end‐organ dysfunction 2. Limiting symptoms due to COVID‐19 1. No limiting symptoms due to COVID‐19 Primary review outcomes All‐cause mortality at hospital discharge: NR 30‐day mortality: yes (day 28) Secondary review outcomes Clinical status, assessed by need for respiratory support with standardised scales (e.g. WHO Clinical Progression Scale, WHO Ordinal Scale for Clinical Improvement at up to 7 days, 8 to 15 days, 16 to 30 days: partially (see primary study outcomes) Mortality (time to event): NR 90‐day mortality: NR Time to discharge from hospital: NR Admission to the intensive care unit (ICU): NR Length of stay on the ICU: NR Viral clearance, assessed with RT‐PCR test at baseline, up to 3, 7, and 15 days: NR QoL: NR Number of participants with grade 3 and grade 4 adverse events, including potential relationship between intervention and adverse reaction (e.g. transfusion‐related acute lung injury (TRALI), transfusion‐transmitted infection, transfusion‐associated circulatory overload (TACO), transfusion‐associated dyspnoea (TAD), acute transfusion reactions): yes Number of participants with serious adverse events: yes Additional study outcomes Clinical status on ordinal scale (see: primary study outcome) (days 3, 5, 14, 28) Change in National Early Warning Score (NEWS) (day 0 to day 7) Time to worsening of at least 3 favourable categories on the primary ordinal scale (see: primary study outcome) (days 7, 14, 28) Percentage of discharged patients (days 7, 14, 28) Days alive outside the hospital  (up to 28 days) Pulmonary‐only components of the primary ordinal outcome (days 3, 5, 7, 14, 28) Thrombotic components of the primary ordinal outcome (days 3, 5, 7, 14, 28) Time to recovery, defined as the 2 most favourable categories on the primary ordinal scale (days 7, 14, 28) Clinical organ dysfunction, defined as new onset of any one or more of the following (up to day 28) A) Respiratory dysfunction B) Cardiac and vascular dysfunction C) Renal dysfunction D) Hepatic dysfunction E) Neurological dysfunction F) Haematological dysfunction G) Serious infection Infusion reactions, interruptions, or cessation (days 1,  3, 7, 28) Change in neutralizing antibody level (days 1,  3, 7, 28)
Starting date	8 October 2020
Contact information	Corresponding author Name: Jacqueline Nordwall Affiliation: NR Full Address: NR Email: jacquie@ccbr.umn.edu
Notes	Recruitment status: recruiting Prospective completion date: July 2021 Sponsor/funding: University of Minnesota, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), The International Network for Strategic Initiatives in Global HIV Trials