COVID-19
Conditions
Interventions
The hIVIG product is administered as a single dose of 400 mg/kg (or 0.4 g/kg) body weight, to a maximum dose of 40 g or 400 mL (i.e. capped at a body weight of 100kg).
Remdesivir will be administered
remdesivir may have commenced prior to randomization. For participants starting remdesivir after randomization to hIVIG/placebo, the loading dose should be given immediately after the infusion of hIVI
for those who commenced remdesivir prior to randomization, the usual maintenance dose of 100 mg can be given after the hIVIG/placebo infusion on Day 0 in the same manner. After the first remdesivir in
shorter durations of 5 days may be considered by the clinical investigator as appropriate in patients who are not ventilated. Infusions will not be given to participants after discharge. The total tre
Sponsors
Ohmagari Norio
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. Symptomatic COVID-19 disease 3. Duration of symptoms attributable to COVID-19 = 18 years 6. Willingness to abstain from participation in other COVID-19 treatment trials until after study Day 7 7. Provision of informed consent by participant or legally authorized representative
Exclusion criteria
Exclusion criteria: 1. Prior receipt of SARS-CoV-2 hIVIG or convalescent plasma from a person who recovered from COVID-19 at any time 2. Prior receipt of standard IVIG (not hyperimmune to SARS-CoV-2) within 45 days 3. 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 4. History of allergy to IVIG or plasma products 5. History of selective IgA deficiency with documented presence of anti-IgA antibodies 6. 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 7. 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 8. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective is to compare the clinical status of participants in the hIVIG + SOC and placebo + SOC groups on Day 7 using an ordinal outcome with 7 mutually exclusive categories. On Day 7, the worst of the 7 categories the participant was in that day will constitute the primary outcome. The 7 categories are: 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives will be assessed by comparing hIVIG + SOC with placebo + SOC over the 28 day follow-up period for outcomes listed below. 1. All-cause mortality through Day 28. 2. The primary ordinal outcome on Days 3, 5, 14 and 28. 3. Change in National Early Warning Score (NEWS) (see Appendix G) from baseline at Day 3. 4. Time to the 3 least favorable categories of the primary outcome measure. 5. Time to the 2 most favorable categories of the primary outcome measure. 6. Hospitalization status (a binary outcome, alive and discharged from the hospital to home or rehabilitation versus dead or hospitalized) at Days 7, 14 and 28. 7. Time to discharge (this is similar to the recovery outcome used in the ACTT-1 trial) 8. Days alive outside of a hospital through Day 28 9. Pulmonary only components of the primary outcome measure at Days 3, 5, 7, 14 and 28 10. Thrombotic components of the primary outcome measure (stroke, myocardial infarction, venous and arterial thrombosis or embolism, plus disseminated intravascular coagulation) at Days 3, 5, 7, 14, and 28. 11. Outcomes assessed in other treatment trials of COVID-19 for hospitalized participants in order to facilitate cross trial comparisons and overviews, e.g., 6-, 7- and 8- category ordinal scales at days 7, 14 and 28; and binary outcomes defined by improvement or worsening based on the primary ordinal outcome and ordinal outcomes used in other trials. 12. Clinical organ dysfunction defined by new onset of any one or more of the following conditions (or requirement for the following therapies) through Day 28: a. Respiratory:1. Extracorporeal membrane oxygenation (ECMO), 2. Invasive ventilation, 3. Non-invasive ventilation or high flow oxygen b. Cardiac and vascular:1. Myocardial infarction, 2. Myocarditis or pericarditis, 3. NYHA Class III/IV congestive cardiac failure, 4. Vasopressor therapy c. Renal: 1. Renal replacement therapy (dialysis) d. Hepatic:1. Hepatic decompensation e. Neurological:1. Cerebrovascul | — |
Countries
Argentina, Denmark, Germany, Greece, India, Indonesia, Israel, Japan, Nigeria, Spain, Thailand, United Kingdom, United States
Contacts
Public ContactSho Saito
Center Hospital of National Center for Global Health and Medicine
Outcome results
None listed