Evaluating the Safety and Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults Hospitalized With Influenza
Condition: Influenza A; Influenza B
MeSH terms: Influenza, Human
Intervention: Intravenous hyperimmune immunoglobulin (IVIG); Placebo for IVIG
Intervention description: Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight); Administered IV as 500 mL of normal saline
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 329.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Antiviral; IVIG; Hemagglutination inhibition (HAI); Antibody

Summary:

      Influenza (the flu) is a common illness that usually occurs in autumn and winter. The flu is
      usually mild, but can cause serious illness or death. The purpose of this study is to test
      the safety and effectiveness of an antibody against the flu (called intravenous hyperimmune
      immunoglobulin or IVIG) in people who are hospitalized for severe flu.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent

          -  Locally determined positive influenza test (by polymerase chain reaction [PCR] or
             other nucleic acid test, or by rapid antigen [Ag]) from a specimen obtained within 2
             days prior to randomization

          -  Onset of illness no more than 7 days before randomization, defined as when the
             participant first experienced at least one respiratory symptom or fever

          -  Hospitalized (or in observation unit) for influenza, with anticipated hospitalization
             for more than 24 hours. Criteria for hospitalization will be up to the individual
             treating clinician.

          -  For women of child-bearing potential: willingness to abstain from sexual intercourse
             or use at least one form of hormonal or barrier contraception through Day 28 of the
             study

          -  Willingness to have blood and respiratory samples obtained and stored

          -  NEW score greater than or equal to 2 at screening (see the protocol for more
             information on this criterion)

        Exclusion Criteria:

          -  Women who are pregnant or breast-feeding

          -  Strong clinical evidence (in the judgment of the site investigator) that the etiology
             of illness is primarily bacterial in origin

          -  Prior treatment with any investigational drug therapy within 30 days prior to
             screening

          -  History of allergic reaction to blood or plasma products (as judged by the site
             investigator)

          -  Known immunoglobulin A (IgA) deficiency

          -  A pre-existing condition or use of a medication that, in the opinion of the site
             investigator, may place the participant at a substantially increased risk of
             thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or
             clinically significant monoclonal gammopathy)

          -  Presence of any pre-existing illness that, in the opinion of the site investigator,
             would place the participant at an unreasonably increased risk through participation in
             this study

          -  Participants who, in the judgment of the site investigator, will be unlikely to comply
             with the requirements of this protocol

          -  Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be
             dangerous to the participant (e.g., decompensated congestive heart failure)

          -  Receiving extracorporeal membrane oxygenation (ECMO)

          -  Suspicion that infection is due to an influenza strain or subtype other than
             A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)