Covid-19 Living Data

Trial NCT04546581
Publication ITAC (INSIGHT 013) - Polizzotto MN, Lancet (2022) (published paper)
Dates: 2020-10-08 to 2021-02-10
Funding: Mixed (US National Institutes of Health. Trial medications were donated by CSL Behring, Emergent BioSolutions, Grifols, Takeda, and Gilead Sciences. Many authors were employees of these companies.)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / Argentina, Denmark, Germany, Greece, Indonesia, Israel, Japan, Nigeria, Spain, UK, USA. Follow-up duration (days): 28
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) Age ≥ 18 years Willingness to abstain from participation in other COVID-19 treatment trials until after study Day 7 Provision of informed consent by participant or legally authorized 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 Prior receipt of any SARS-CoV-2 monoclonal antibody treatments at any time (24 November 2020 Letter of Amendment) 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 Heart 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 randomization 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 participant or that could prevent, limit, or confound the protocol-specified assessments
Interventions
	Treatment C-IVIG 400 mg/kg once-off, capped at 40 g. Commenced at rate of 0·5 mg/kg per min for 30 mins; if tolerated, doubled at 30 min intervals to maximum of 4 mg/kg per min.
	Control Placebo
Participants
	Randomized participants : Placebo=292 C-IVIG=301
	Characteristics of participants N= 593 Mean age : NR 336 males Severity : Mild: n=166 / Moderate: n=369 / Severe: n=58 Critical: n=0 Number of vaccinated participants: 3
Primary outcome
	In the register Ordinal Outcome Scale - Day 7 [ Time Frame: 7 days ] The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 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. Outcome is reported as the percent of participants in each of 7 categories.
	In the report An ordinal outcome based on the patient's clinical status on day 7. The seven categories of this outcome ranged from return to usual activities with no more than minimal symptoms due to COVID-19, to death. Primary safety outcome was a composite of death, serious adverse events, and grade 3 or 4 adverse events up to day 7.
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, the registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. The primary outcome in the article reflects that in the registry. The study (n = 593) achieved its target sample size (n = 500). This study was updated on September 28th, 2022 with data extracted from the registry (SAE results).