Comparing the Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Treatment of Severe Influenza A
Condition: Influenza A Virus Infection
MeSH terms: Influenza, Human
Intervention: High-titer anti-influenza plasma; Low-titer anti-influenza plasma
Intervention description: Human plasma (FFP or FP24, 225-350 mL per unit or pediatric equivalent) with both an influenza A/H1N1 and A/H3N2 HAI titer of at least 1:80; Human plasma (FFP or FP24, 225-350 mL per unit or pediatric equivalent) with both an influenza A/H1N1 and A/H3N2 HAI titer of 1:10 or less
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 138.0
Sex: All
Minimum age: 2 Weeks
Healthy volunteers: No
Keywords: Anti-Influenza Immune Plasma

Summary:

      This study assessed the efficacy and safety of anti-influenza immune plasma, as an addition
      to standard of care antivirals, in participants hospitalized with severe influenza A
      infection.
    

Eligibility criteria:

        Inclusion Criteria for Enrollment (Screening):

          -  Subjects must be aged 2 weeks or older.

          -  Hospitalization due to signs and symptoms of influenza.

             * Note: The decision for hospitalization will be made by the treating clinician. To be
             considered eligible, the hospitalization may either be an initial hospitalization, or
             a prolongation of a hospitalization due to a respiratory illness that was found to be
             from influenza. Influenza could be a component of a larger respiratory syndrome (i.e.
             COPD exacerbation thought to be triggered by influenza). However, respiratory
             syndromes that are not likely due to the virus should not be included (i.e. a subject
             that had mild influenza then developed pulmonary embolism and respiratory distress
             from the embolism).

          -  Study plasma available on-site or available within 24 hours after randomization.

          -  Not previously screened nor randomized in this study.

          -  Willingness to have blood and respiratory samples obtained and stored.

          -  Willingness to return for all required study visits and participate in study follow
             up.

        Inclusion Criteria for Randomization:

          -  Locally determined positive test for influenza A (by polymerase chain reaction [PCR],
             other nucleic acid testing, or by rapid Ag) from a specimen obtained less than or
             equal to 48 hours prior to randomization.

          -  Onset of illness less than or equal to 6 days before randomization, defined as when
             the subject first experienced at least one respiratory symptom or fever.

          -  Note: For subjects with chronic respiratory symptoms (chronic cough, or COPD with
             baseline dyspnea), the onset of symptoms is defined as the point when the symptoms
             changed during this illness). Hospitalized due to influenza, with anticipated
             hospitalization for more than 24 hours after randomization. Criteria for
             hospitalization will be up to the individual treating clinician.

          -  National Early Warning (NEW) or Pediatric Early Warning (PEW) score greater than or
             equal to 3 within 12 hours prior to randomization.

          -  ABO-compatible plasma available on-site or available within 24 hours after
             randomization.

        Exclusion Criteria for Randomization:

          -  Strong clinical evidence in the judgment of the site investigator that the etiology of
             illness is primarily bacterial super-infection in origin. Co-infection would be
             allowed, as there may be benefit to resolving influenza illness faster.
             Super-infection, where influenza illness occurred and is resolving, and new bacterial
             illness causing deterioration should be excluded (e.g., if the subject's respiratory
             infection is thought unlikely to benefit from additional antiviral therapy, this
             exclusion criteria would be met).

          -  Prior treatment with any anti-influenza investigational drug, anti-influenza
             investigational intravenous immune globulin (IVIG), or anti-influenza investigational
             plasma therapy within 30 days prior to screening. Other investigational drug therapies
             (non-influenza) and administration of plasma and/or IVIG for non-influenza reasons are
             allowed.

          -  History of allergic reaction to blood or plasma products (as judged by the site
             investigator).

          -  A pre-existing condition or use of a medication that, in the opinion of the site
             investigator, may place the individual at a substantially increased risk of thrombosis
             (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically
             significant monoclonal gammopathy). Prior IVIG use alone would not meet exclusion
             criteria, but the investigator should consider the potential for a hyper-coagulable
             state.

          -  Subjects who, in the judgment of the site investigator, will be unlikely to comply
             with the requirements of this protocol, including being not contactable following
             discharge from hospital.

          -  Medical conditions for which receipt of 500-600 mL (or pediatric equivalent) of
             intravenous fluid may be dangerous to the subject (e.g., decompensated congestive
             heart failure).