Influenza A Virus Infection
Conditions
Keywords
Anti-Influenza Immune Plasma
Brief 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.
Detailed description
Despite antivirals and vaccines, influenza is responsible for thousands of hospitalizations and deaths each year worldwide. Because of this, additional treatments for influenza are needed. One potential treatment may be the use of high-titer anti-influenza immune plasma. The purpose of this study is to evaluate the efficacy and safety of treatment with high-titer versus low-titer anti-influenza immune plasma, in addition to standard care, in participants hospitalized with severe influenza A infection. This study enrolled people aged 2 weeks or older who are hospitalized with severe influenza A infection. Participants were randomly assigned to receive either high-titer anti-influenza plasma or low-titer (control) anti-influenza plasma on Day 0. In addition, all participants received standard care antivirals. Participants were assessed on Day 0 (baseline) and on Days 1, 2, 3, 7, 14, and 28. For participants who were not hospitalized on Days 2, 14, and 28, researchers could contact participants by telephone. Study procedures included clinical assessments, blood collection, and oropharyngeal swabs.
Interventions
BIOLOGICALHigh-titer anti-influenza plasma
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
BIOLOGICALLow-titer anti-influenza plasma
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
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Weeks to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Status at Day 7 | Day 7 | The clinical status at Day 7 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Initial Hospitalization | From Day 0 to Day 28 | Duration (in days) of initial hospitalization, restricted to duration between randomization and last visit |
| 28-day Mortality | From Day 0 to Day 28 | Number of deaths during study follow-up |
| Clinical Status at Day 28 | Day 28 | The clinical status at Day 28 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome |
| Clinical Status at Day 1 | Day 1 | The clinical status at Day 1 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome |
| Clinical Status at Day 2 | Day 2 | The clinical status at Day 2 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome |
| Clinical Status at Day 3 | Day 3 | The clinical status at Day 3 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome |
| Clinical Status at Day 14 | Day 14 | The clinical status at Day 14 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome |
| In-hospital Mortality During Initial Hospitalization | From Day 0 to Day 28 | Number of deaths in the hospital during initial hospitalization |
| Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Day 7, Day 14, Day 28 | Two categories were considered for the composite of mortality and hospitalization: Dead or hospitalized Alive and not hospitalized |
| Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score | Day 0, Day 3, Day 7 | The National Early Warning (NEW) score was only measured for the adult participants. The range of the NEW score is from 0 to 20, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline. |
| Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score | Day 0, Day 3, Day 7 | The Pediatric Early Warning (PEW) score was only measured for the pediatric participants. The range is from 0 to 26, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline. |
| Duration of Supplemental Oxygen | From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry. | Duration (in days) of total supplemental oxygen use among those participants who required new or increased oxygen at randomization. The duration is restricted to duration between randomization and last visit. |
| Incidence of New Oxygen Use During the Study | From Day 0 to Day 28 | Incidence of new oxygen use during the study among those participants who did not require oxygen at randomization |
| Duration of Intensive Care Unit (ICU) Stay | From Day 0 to Day 28 | Duration (in days) of ICU stay among those participants who were in ICU at randomization. The duration is restricted to duration between randomization and last visit. |
| Incidence of New ICU Admission Use During the Study | From Day 0 to Day 28 | Incidence of new ICU admission during the study among those participants who were not in ICU at randomization |
| Duration of Mechanical Ventilation Use | From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry | Duration (in days) of mechanical ventilation use among those participants who were on mechanical ventilation at randomization. The duration is restricted to duration between randomization and last visit. |
| Incidence of New Mechanical Ventilation Use Stay Use During the Study | From Day 0 to Day 28 | Incidence of new mechanical ventilation use during the study among those participants who were not on mechanical ventilation at randomization |
| Duration of Acute Respiratory Distress Syndrome (ARDS) | From Day 0 to Day 28 | Duration (in days) of ARDS use among those participants with ARDS at randomization. The duration is restricted to duration between randomization and last visit. |
| Incidence of New ARDS During the Study | From Day 0 to Day 28 | Incidence of new ARDS during the study among those participants without ARDS at randomization |
| Duration of Extracorporeal Membrane Oxygenation (ECMO) | From Day 0 to Day 28 | Duration (in days) of ECMO use among those participants on ECMO at randomization. The duration is restricted to duration between randomization and last visit. |
| Incidence of New ECMO Use During the Study | From Day 0 to Day 28 | Incidence of new ECMO use during the study among those participants not on ECMO at randomization |
| Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score | Day 0, Day 3, Day 7 | The Sequential Organ Failure Assessment (SOFA) score was only measured for the adult participants. The range is from 0 to 24, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline. |
| Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score | Day 0, Day 3, Day 7 | The Pediatric Logistic Organ Dysfunction (PELOD) score was only measured for the pediatric participants. The range is from 0 to 71, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline. |
| Disposition After Initial Hospitalization | From Day 0 to Day 28 | Disposition at discharge after initial hospitalization was categorized as follows: Death, Ongoing at 28 days, Chronic nursing facility, Rehabilitation, Home with home health care, Home without assistance. The number of deaths at discharge after initial hospitalization do not necessarily match the overall number of deaths. |
| Detectable Influenza Virus at Day 3 | Day 3 | Detectable influenza virus at Day 3 in oropharyngeal samples |
| Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1 | Day 1, Day 3, Day 7 | Hemagglutination inhibition assay (HAI) titers as measured by serial dilutions at Days 1, 3, 7 for A/H1N1. HAI for A/H1N1 was tested in all influenza seasons while the study was ongoing. |
| Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2 | Day 1, Day 3, Day 7 | Hemagglutination inhibition assay (HAI) titers as measured by serial dilutions at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2. HAI for A/HongKong/4801/2014 H3N2 was tested in all influenza seasons while the study was ongoing. |
| Number of Participants With Grade 3 and 4 Adverse Events (AEs). | From Day 0 to Day 28 | Number of participants with reported grade 3 and 4 adverse events (AEs) throughout the study duration. In cases where participants had multiple reports of grade 3 and 4 AEs, they were only counted once. |
| Number of Participants With Serious Adverse Events (SAEs). | From Day 0 to Day 28 | Number of participants with reported serious adverse events (SAEs) throughout the study duration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-titer Anti-influenza Plasma mITT High-titer anti-influenza mITT (modified intent to treat) is the subgroup of high-titer anti-influenza plasma participants who received any study plasma | 91 |
| Low-titer Anti-influenza Plasma mITT Low-titer anti-influenza mITT (modified intent to treat) is the subgroup of low-titer anti-influenza plasma participants who received any study plasma | 47 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 3 |
| Overall Study | Lost to Follow-up | 3 | 3 |
Baseline characteristics
| Characteristic | High-titer Anti-influenza Plasma mITT | Low-titer Anti-influenza Plasma mITT | Total |
|---|---|---|---|
| Age, Continuous | 58 years | 63 years | 61 years |
| Age, Customized < 18 years | 8 Participants | 5 Participants | 13 Participants |
| Age, Customized ≥ 18 years | 83 Participants | 42 Participants | 125 Participants |
| Baseline National Early Warning (NEW) score | 5 units on a scale | 5 units on a scale | 5 units on a scale |
| Baseline Pediatric Early Warning (PEW) score | 9 units on a scale | 8 units on a scale | 8 units on a scale |
| Baseline Pediatric Logistic Organ Dysfunction (PELOD) Score | 0 units on a scale | 3 units on a scale | 0.5 units on a scale |
| Baseline Sequential Organ Failure Assessment (SOFA) Score | 3 units on a scale | 3 units on a scale | 3 units on a scale |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 16 Participants | 8 Participants | 24 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 69 Participants | 36 Participants | 105 Participants |
| Region of Enrollment United States | 91 participants | 47 participants | 138 participants |
| Sex: Female, Male Female | 41 Participants | 26 Participants | 67 Participants |
| Sex: Female, Male Male | 50 Participants | 21 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 91 | 4 / 47 |
| other Total, other adverse events | 0 / 91 | 0 / 47 |
| serious Total, serious adverse events | 31 / 91 | 15 / 47 |
Outcome results
Primary
Clinical Status at Day 7
The clinical status at Day 7 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome
Time frame: Day 7
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment (with available data).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Non-ICU hospitalization without supplemental O2 | 8 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Death | 2 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Not hospitalized, unable for normal activity | 30 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Not hospitalized, able for normal activity | 20 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | in ICU | 15 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Non-ICU hospitalization with supplemental O2 | 16 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Not hospitalized, able for normal activity | 11 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Non-ICU hospitalization without supplemental O2 | 5 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Non-ICU hospitalization with supplemental O2 | 7 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Death | 2 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | in ICU | 10 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 7 | Not hospitalized, unable for normal activity | 11 Participants |
p-value: 0.5495% CI: [0.65, 2.29]Regression, Logistic
Secondary
28-day Mortality
Number of deaths during study follow-up
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | 28-day Mortality | 6 Participants |
| Low-titer Anti-influenza Plasma mITT | 28-day Mortality | 4 Participants |
p-value: 0.6495% CI: [0.21, 2.64]Log Rank
Secondary
Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score
The National Early Warning (NEW) score was only measured for the adult participants. The range of the NEW score is from 0 to 20, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline.
Time frame: Day 0, Day 3, Day 7
Population: Modified intent-to-treat adult population: subgroup of randomized adult participants who received any study treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score | Change in NEW from baseline to Day 3 | -2 units on a scale |
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score | Change in NEW from baseline to Day 7 | -2 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score | Change in NEW from baseline to Day 3 | -1 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score | Change in NEW from baseline to Day 7 | -2 units on a scale |
Comparison: Change in NEW from baseline to Day 3p-value: 0.295% CI: [-2, 0]Wilcoxon (Mann-Whitney)
Comparison: Change in NEW from baseline to Day 3p-value: 0.6695% CI: [-1, 1]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score
The Pediatric Early Warning (PEW) score was only measured for the pediatric participants. The range is from 0 to 26, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline.
Time frame: Day 0, Day 3, Day 7
Population: Modified intent-to-treat pediatric population: subgroup of randomized pediatric participants who received any study treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score | Change in PEW from baseline to Day 3 | 0 units on a scale |
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score | Change in PEW from baseline to Day 7 | -4.5 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score | Change in PEW from baseline to Day 3 | -1 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score | Change in PEW from baseline to Day 7 | -5 units on a scale |
Comparison: Change in PEW from baseline to Day 3p-value: 0.18Wilcoxon (Mann-Whitney)
Comparison: Change in PEW from baseline to Day 7p-value: 0.61Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score
The Pediatric Logistic Organ Dysfunction (PELOD) score was only measured for the pediatric participants. The range is from 0 to 71, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline.
Time frame: Day 0, Day 3, Day 7
Population: Modified intent-to-treat pediatric population: subgroup of randomized pediatric participants who received any study treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score | Change in PELOD from baseline to Day 3 | 0 units on a scale |
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score | Change in PELOD from baseline to Day 7 | 0 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score | Change in PELOD from baseline to Day 3 | 10 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score | Change in PELOD from baseline to Day 7 | 0 units on a scale |
Comparison: Change in PELOD from baseline to Day 3p-value: 0.36Wilcoxon (Mann-Whitney)
Comparison: Change in PELOD from baseline to Day 7p-value: 0.15Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score
The Sequential Organ Failure Assessment (SOFA) score was only measured for the adult participants. The range is from 0 to 24, with lower values representing a better outcome. Baseline is defined as the Day 0. Change was defined as the value at Day 3 or Day 7 minus the value at baseline.
Time frame: Day 0, Day 3, Day 7
Population: Modified intent-to-treat adult population: subgroup of randomized adult participants who received any study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score | Change in SOFA from baseline to Day 7 | -1 units on a scale |
| High-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score | Change in SOFA from baseline to Day 3 | 0 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score | Change in SOFA from baseline to Day 7 | 0 units on a scale |
| Low-titer Anti-influenza Plasma mITT | Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score | Change in SOFA from baseline to Day 3 | 0 units on a scale |
Comparison: Change in SOFA from baseline to Day 3p-value: 0.0695% CI: [-1, 0]Wilcoxon (Mann-Whitney)
Comparison: Change in SOFA from baseline to Day 7p-value: 0.1395% CI: [-1, 0]Wilcoxon (Mann-Whitney)
Secondary
Clinical Status at Day 1
The clinical status at Day 1 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome
Time frame: Day 1
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Death | 0 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Non-ICU hospitalization with supplemental O2 | 30 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | in ICU | 38 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Non-ICU hospitalization without supplemental O2 | 21 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Not hospitalized, unable for normal activity | 2 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Not hospitalized, able for normal activity | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Not hospitalized, unable for normal activity | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Death | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Non-ICU hospitalization without supplemental O2 | 14 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Not hospitalized, able for normal activity | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | in ICU | 18 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 1 | Non-ICU hospitalization with supplemental O2 | 14 Participants |
p-value: 0.6695% CI: [0.45, 1.66]Regression, Logistic
Secondary
Clinical Status at Day 14
The clinical status at Day 14 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome
Time frame: Day 14
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Death | 4 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | in ICU | 10 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Non-ICU hospitalization with supplemental O2 | 3 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Non-ICU hospitalization without supplemental O2 | 6 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Not hospitalized, unable for normal activity | 26 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Not hospitalized, able for normal activity | 37 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Not hospitalized, unable for normal activity | 12 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Death | 4 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Non-ICU hospitalization without supplemental O2 | 1 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | in ICU | 6 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Not hospitalized, able for normal activity | 20 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 14 | Non-ICU hospitalization with supplemental O2 | 2 Participants |
p-value: 0.8395% CI: [0.55, 2.08]Regression, Logistic
Secondary
Clinical Status at Day 2
The clinical status at Day 2 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome
Time frame: Day 2
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Death | 1 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | in ICU | 35 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Non-ICU hospitalization with supplemental O2 | 24 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Not hospitalized, unable for normal activity | 6 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Not hospitalized, able for normal activity | 6 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Non-ICU hospitalization without supplemental O2 | 19 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Non-ICU hospitalization without supplemental O2 | 13 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Death | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Not hospitalized, able for normal activity | 1 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | in ICU | 17 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Not hospitalized, unable for normal activity | 3 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 2 | Non-ICU hospitalization with supplemental O2 | 12 Participants |
p-value: 0.8795% CI: [0.5, 1.8]Regression, Logistic
Secondary
Clinical Status at Day 28
The clinical status at Day 28 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome
Time frame: Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Not hospitalized, unable for normal activity | 24 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Death | 6 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Non-ICU hospitalization without supplemental O2 | 2 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | in ICU | 5 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Not hospitalized, able for normal activity | 51 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Non-ICU hospitalization with supplemental O2 | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Not hospitalized, able for normal activity | 24 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Non-ICU hospitalization without supplemental O2 | 1 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Not hospitalized, unable for normal activity | 11 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Non-ICU hospitalization with supplemental O2 | 2 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | Death | 4 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 28 | in ICU | 3 Participants |
p-value: 0.4795% CI: [0.65, 2.56]Regression, Logistic
Secondary
Clinical Status at Day 3
The clinical status at Day 3 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome
Time frame: Day 3
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Not hospitalized, unable for normal activity | 11 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | in ICU | 29 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Non-ICU hospitalization with supplemental O2 | 20 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Non-ICU hospitalization without supplemental O2 | 17 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Not hospitalized, able for normal activity | 12 Participants |
| High-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Death | 1 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Not hospitalized, able for normal activity | 2 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Death | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Not hospitalized, unable for normal activity | 4 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | in ICU | 15 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Non-ICU hospitalization without supplemental O2 | 12 Participants |
| Low-titer Anti-influenza Plasma mITT | Clinical Status at Day 3 | Non-ICU hospitalization with supplemental O2 | 10 Participants |
p-value: 0.4995% CI: [0.65, 2.41]Regression, Logistic
Secondary
Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28
Two categories were considered for the composite of mortality and hospitalization: Dead or hospitalized Alive and not hospitalized
Time frame: Day 7, Day 14, Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 14 | Dead or hospitalized | 23 Participants |
| High-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 7 | Dead or hospitalized | 41 Participants |
| High-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 7 | Alive and not hospitalized | 50 Participants |
| High-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 14 | Alive and not hospitalized | 63 Participants |
| High-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 28 | Alive and not hospitalized | 75 Participants |
| High-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 28 | Dead or hospitalized | 13 Participants |
| Low-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 28 | Alive and not hospitalized | 35 Participants |
| Low-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 7 | Alive and not hospitalized | 22 Participants |
| Low-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 28 | Dead or hospitalized | 10 Participants |
| Low-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 7 | Dead or hospitalized | 24 Participants |
| Low-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 14 | Dead or hospitalized | 13 Participants |
| Low-titer Anti-influenza Plasma mITT | Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28 | Composite mortality and hospitalization, Day 14 | Alive and not hospitalized | 32 Participants |
Comparison: Composite mortality and hospitalization, Day 7p-value: 0.4395% CI: [0.65, 2.71]Regression, Logistic
Comparison: Composite mortality and hospitalization, Day 14p-value: 0.7995% CI: [0.5, 2.48]Regression, Logistic
Comparison: Composite mortality and hospitalization, Day 28p-value: 0.2995% CI: [0.66, 4.12]Regression, Logistic
Secondary
Detectable Influenza Virus at Day 3
Detectable influenza virus at Day 3 in oropharyngeal samples
Time frame: Day 3
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment. This group was further subset wo those with available OP sample results at Day 3.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Detectable Influenza Virus at Day 3 | Detectable | 65 Participants |
| High-titer Anti-influenza Plasma mITT | Detectable Influenza Virus at Day 3 | Undetectable | 20 Participants |
| Low-titer Anti-influenza Plasma mITT | Detectable Influenza Virus at Day 3 | Detectable | 35 Participants |
| Low-titer Anti-influenza Plasma mITT | Detectable Influenza Virus at Day 3 | Undetectable | 5 Participants |
p-value: 0.2395% CI: [0.13, 1.43]Regression, Logistic
Secondary
Disposition After Initial Hospitalization
Disposition at discharge after initial hospitalization was categorized as follows: Death, Ongoing at 28 days, Chronic nursing facility, Rehabilitation, Home with home health care, Home without assistance. The number of deaths at discharge after initial hospitalization do not necessarily match the overall number of deaths.
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Death | 4 Participants |
| High-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Ongoing at 28 days | 3 Participants |
| High-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Chronic nursing facility/ | 7 Participants |
| High-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Rehabilitation | 4 Participants |
| High-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Home with home health care | 13 Participants |
| High-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Home without assistance | 60 Participants |
| Low-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Home with home health care | 8 Participants |
| Low-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Death | 4 Participants |
| Low-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Rehabilitation | 3 Participants |
| Low-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Ongoing at 28 days | 3 Participants |
| Low-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Home without assistance | 25 Participants |
| Low-titer Anti-influenza Plasma mITT | Disposition After Initial Hospitalization | Chronic nursing facility/ | 4 Participants |
p-value: 0.1295% CI: [0.87, 3.44]Regression, Logistic
Secondary
Duration of Acute Respiratory Distress Syndrome (ARDS)
Duration (in days) of ARDS use among those participants with ARDS at randomization. The duration is restricted to duration between randomization and last visit.
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants with ARDS at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Duration of Acute Respiratory Distress Syndrome (ARDS) | 9 days |
| Low-titer Anti-influenza Plasma mITT | Duration of Acute Respiratory Distress Syndrome (ARDS) | 8 days |
Secondary
Duration of Extracorporeal Membrane Oxygenation (ECMO)
Duration (in days) of ECMO use among those participants on ECMO at randomization. The duration is restricted to duration between randomization and last visit.
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who were on ECMO at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Duration of Extracorporeal Membrane Oxygenation (ECMO) | 16 days |
| Low-titer Anti-influenza Plasma mITT | Duration of Extracorporeal Membrane Oxygenation (ECMO) | 20 days |
Secondary
Duration of Initial Hospitalization
Duration (in days) of initial hospitalization, restricted to duration between randomization and last visit
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Duration of Initial Hospitalization | 5 days |
| Low-titer Anti-influenza Plasma mITT | Duration of Initial Hospitalization | 6 days |
p-value: 0.3Wilcoxon (Mann-Whitney)
Secondary
Duration of Intensive Care Unit (ICU) Stay
Duration (in days) of ICU stay among those participants who were in ICU at randomization. The duration is restricted to duration between randomization and last visit.
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who were in the ICU at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Duration of Intensive Care Unit (ICU) Stay | 5 days |
| Low-titer Anti-influenza Plasma mITT | Duration of Intensive Care Unit (ICU) Stay | 8 days |
p-value: 0.3795% CI: [-6, 2]Wilcoxon (Mann-Whitney)
Secondary
Duration of Mechanical Ventilation Use
Duration (in days) of mechanical ventilation use among those participants who were on mechanical ventilation at randomization. The duration is restricted to duration between randomization and last visit.
Time frame: From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who were on mechanical ventilation at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Duration of Mechanical Ventilation Use | 9 days |
| Low-titer Anti-influenza Plasma mITT | Duration of Mechanical Ventilation Use | 15.5 days |
p-value: 0.2295% CI: [-14, 2]Wilcoxon (Mann-Whitney)
Secondary
Duration of Supplemental Oxygen
Duration (in days) of total supplemental oxygen use among those participants who required new or increased oxygen at randomization. The duration is restricted to duration between randomization and last visit.
Time frame: From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry.
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who required new or increased oxygen at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Duration of Supplemental Oxygen | 6 days |
| Low-titer Anti-influenza Plasma mITT | Duration of Supplemental Oxygen | 7 days |
p-value: 0.6895% CI: [-2, 1]Wilcoxon (Mann-Whitney)
Secondary
Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1
Hemagglutination inhibition assay (HAI) titers as measured by serial dilutions at Days 1, 3, 7 for A/H1N1. HAI for A/H1N1 was tested in all influenza seasons while the study was ongoing.
Time frame: Day 1, Day 3, Day 7
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1 | Day 1 | 46.9 ratios |
| High-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1 | Day 3 | 50.6 ratios |
| High-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1 | Day 7 | 63.1 ratios |
| Low-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1 | Day 1 | 19.7 ratios |
| Low-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1 | Day 3 | 23.7 ratios |
| Low-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1 | Day 7 | 37.1 ratios |
Secondary
Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2
Hemagglutination inhibition assay (HAI) titers as measured by serial dilutions at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2. HAI for A/HongKong/4801/2014 H3N2 was tested in all influenza seasons while the study was ongoing.
Time frame: Day 1, Day 3, Day 7
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2 | Day 1 | 53.7 ratios |
| High-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2 | Day 3 | 55.2 ratios |
| High-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2 | Day 7 | 75.7 ratios |
| Low-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2 | Day 1 | 22.4 ratios |
| Low-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2 | Day 3 | 36.8 ratios |
| Low-titer Anti-influenza Plasma mITT | Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2 | Day 7 | 53 ratios |
Secondary
Incidence of New ARDS During the Study
Incidence of new ARDS during the study among those participants without ARDS at randomization
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants without ARDS at randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Incidence of New ARDS During the Study | Yes | 3 Participants |
| High-titer Anti-influenza Plasma mITT | Incidence of New ARDS During the Study | No | 72 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New ARDS During the Study | Yes | 5 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New ARDS During the Study | No | 39 Participants |
p-value: 0.2495% CI: [0.05, 1.79]Regression, Logistic
Secondary
Incidence of New ECMO Use During the Study
Incidence of new ECMO use during the study among those participants not on ECMO at randomization
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who were not on ECMO at randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Incidence of New ECMO Use During the Study | Yes | 1 Participants |
| High-titer Anti-influenza Plasma mITT | Incidence of New ECMO Use During the Study | No | 85 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New ECMO Use During the Study | Yes | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New ECMO Use During the Study | No | 46 Participants |
p-value: 1Fisher Exact
Secondary
Incidence of New ICU Admission Use During the Study
Incidence of new ICU admission during the study among those participants who were not in ICU at randomization
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who were not in the ICU at randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Incidence of New ICU Admission Use During the Study | No | 48 Participants |
| High-titer Anti-influenza Plasma mITT | Incidence of New ICU Admission Use During the Study | Yes | 3 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New ICU Admission Use During the Study | Yes | 0 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New ICU Admission Use During the Study | No | 27 Participants |
p-value: 0.55Fisher Exact
Secondary
Incidence of New Mechanical Ventilation Use Stay Use During the Study
Incidence of new mechanical ventilation use during the study among those participants who were not on mechanical ventilation at randomization
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who were not on mechanical ventilation at randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Incidence of New Mechanical Ventilation Use Stay Use During the Study | Yes | 3 Participants |
| High-titer Anti-influenza Plasma mITT | Incidence of New Mechanical Ventilation Use Stay Use During the Study | No | 63 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New Mechanical Ventilation Use Stay Use During the Study | Yes | 2 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New Mechanical Ventilation Use Stay Use During the Study | No | 31 Participants |
p-value: 195% CI: [0.08, 9.29]Regression, Logistic
Secondary
Incidence of New Oxygen Use During the Study
Incidence of new oxygen use during the study among those participants who did not require oxygen at randomization
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment, further subset to those participants who did not require oxygen at randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-titer Anti-influenza Plasma mITT | Incidence of New Oxygen Use During the Study | Yes | 7 Participants |
| High-titer Anti-influenza Plasma mITT | Incidence of New Oxygen Use During the Study | No | 13 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New Oxygen Use During the Study | Yes | 3 Participants |
| Low-titer Anti-influenza Plasma mITT | Incidence of New Oxygen Use During the Study | No | 8 Participants |
p-value: 0.9895% CI: [0.23, 11.01]Regression, Logistic
Secondary
In-hospital Mortality During Initial Hospitalization
Number of deaths in the hospital during initial hospitalization
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | In-hospital Mortality During Initial Hospitalization | 4 Participants |
| Low-titer Anti-influenza Plasma mITT | In-hospital Mortality During Initial Hospitalization | 3 Participants |
p-value: 0.69Fisher Exact
Secondary
Number of Participants With Grade 3 and 4 Adverse Events (AEs).
Number of participants with reported grade 3 and 4 adverse events (AEs) throughout the study duration. In cases where participants had multiple reports of grade 3 and 4 AEs, they were only counted once.
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Number of Participants With Grade 3 and 4 Adverse Events (AEs). | 34 Participants |
| Low-titer Anti-influenza Plasma mITT | Number of Participants With Grade 3 and 4 Adverse Events (AEs). | 14 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs).
Number of participants with reported serious adverse events (SAEs) throughout the study duration.
Time frame: From Day 0 to Day 28
Population: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-titer Anti-influenza Plasma mITT | Number of Participants With Serious Adverse Events (SAEs). | 31 Participants |
| Low-titer Anti-influenza Plasma mITT | Number of Participants With Serious Adverse Events (SAEs). | 15 Participants |