Influenza A, Influenza B
Conditions
Keywords
Antiviral, Anti-Influenza Immune Plasma, Emerging Infectious Disease, Swine Flu
Brief summary
This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza A or B. Hospitalized subjects with influenza A or B that have either a low oxygen level or a high respiratory rate will be eligible for study participation. This study will enroll adults, children and pregnant women.
Detailed description
Morbidity and mortality occur despite treatment with current antivirals. Circulating influenza H1N1 and H3N2 isolates are highly resistant to amantadine and rimantadine, whereas previous seasonal H1N1 isolates were highly resistant to oseltamivir. So there is concern that circulating influenza A/H1N1 2009 virus may also acquire oseltamivir resistance. This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza. Hospitalized subjects with influenza at risk for severe disease (as defined in the inclusion criteria) will be eligible for study participation. This study will enroll adults, children and pregnant women. Up to 40 sites in the United States will participate in this protocol. One hundred eligible subjects will be randomized in a 1:1 ratio to receive either 2 units (or pediatric equivalent) of anti-influenza immune plasma on Study Day 0 in addition to standard care or standard care alone (50 subjects receiving standard care alone; 50 subjects receiving anti-influenza immune plasma and standard care). Subjects will be assessed on Study Day 0 (pre-dose), 30 minutes post-dose (plasma arm only), and on Study Days 1, 2, 4, 7, 14, and 28. All subjects will undergo a series of efficacy, safety, and PK (HAI) assessments during the study. Blood samples will be collected at each time point (except Day 1). Nasal and oropharyngeal swabs for influenza PCR will be obtained on Days 0,1,2,4 and 7.
Interventions
BIOLOGICALAnti-Influenza Immune Plasma
2 units of plasma with high titer anti-influenza A or anti-influenza B antibodies at baseline
DRUGStandard Care
All subjects will receive an anti-influenza antiviral (e.g., oseltamivir or zanamivir), but may include treatment with licensed antivirals in patient populations or at doses not covered in the package insert, or with medications available under a EUA. Standard care may also include antibiotics and other medications.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Diagnosis of influenza A or B within 72 hours prior to enrollment (by local assay including rapid antigen, direct fluorescent antibody (DFA), polymerase chain reaction (PCR), or culture, and must be able to detect and distinguish influenza A from influenza B) * Hospitalization for signs and symptoms of influenza (decision for hospitalization will be up to the individual treating clinician). * Abnormal respiratory status, defined as room air saturation of oxygen (SaO2) less than 93% or tachypnea (respiratory rate above an age adjusted normal range) * Agree to the storage of specimens and data * ABO compatible plasma available on site or available within 24 hours after randomization with activity against locally circulating strains of influenza
Exclusion criteria
* Receipt of non-licensed treatment for influenza within the last 2 weeks (or plans to receive any time during the study). This does not include licensed drugs at non approved doses, off-label indications, or drugs available under an Emergency Use Authorization (EUA). * History of severe allergic reaction to blood products (as judged by the investigator). * Medical conditions for which receipt of 500 mL volume (or 8 mL/kg for pediatric patients) may be dangerous to the subject (e.g. decompensated congestive heart failure \[CHF\], etc.) * Clinical suspicion that etiology of acute illness is primarily due to a condition other than active influenza virus replication (e.g., a bacterial or fungal infection)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Normalization of Respiratory Status (Primary Efficacy Population) | Measured from Day 0 through Day 28 | Normalized respiratory status is defined as room air saturation of oxygen \[SaO2\] greater than or equal to 93% AND respiratory rate within normal ranges. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Time to Resolution of Clinical Symptoms | Measured from Day 0 through Day 28 | The assessed clinical symptoms were nausea, vomiting, diarrhea, sore throat, headache, muscle ache, cough, and shortness of breath. Symptoms were assessed at days 0, 1, 2, 4, 7, 14, and 28. |
| Duration of Time to Resolution of Fever | Measured from Day 0 through Day 28 | Fever was defined as either a temperature \> 38.0 C, or a report of a Grade 1 or higher fever as an adverse event. |
| Duration of Time to Resolution of All Symptoms and Fever | Measured from Day 0 through Day 28 | The assessed symptoms were nausea, vomiting, diarrhea, sore throat, headache, muscle ache, cough, and shortness of breath. Fever was defined as either a temperature \> 38.0 C, or a report of a Grade 1 or higher fever as an adverse event. |
| Time to 20% Improvement in Sequential Organ Failure Assessment (SOFA) Score for Participants >= 18 Years Old and Pediatric Logistic Organ Dysfunction (PELOD) Score for Participants < 18 Years Old | Measured from Day 0 through Day 28 | The analysis is restricted to participants \>= 18 years old and the SOFA score because there were very few evaluations of the PELOD score during follow-up for the participants \< 18 years old. The adult population was further subset to those with a non-missing and non-zero SOFA score at Day 0; those with missing SOFA score at Day 0 did not have a starting point, and those with SOFA = 0 at Day 0 could not have an improvement. |
| 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Measured at Days 1, 2, 4, 7, 14, 28 | Number of participants with ABG done and no increase of 50 millimeters of mercury (mm/Hg) or greater in PaO2/FiO2 ratio. PaO2/FiO2 ratio was evaluated by an ABG. ABG was performed only when clinically indicated. |
| In-hospital Mortality | Measured from Day 0 through Day 28 | Number of deaths in hospital during initial hospital admission |
| 28-day Mortality | Measured from Day 0 through Day 28 | Number of deaths during study follow-up |
| Duration of Hospitalization | Measured from Day 0 through Day 28 | Days that a participant spent at the hospital. Multiple hospitalizations are summed up. |
| Number of ICU Admissions | Measured from Day 0 through Day 28 | Number of ICU admissions during study follow-up. The intent was to analyze any number of ICU admissions. |
| Duration of Stay in ICU | Measured from Day 0 through Day 28 | Days that a participant spent in ICU. Multiple ICU admissions are summed up. |
| Time to Normalization of Respiratory Status (All Randomized Participants) | Measured from Day 0 through Day 28 | Normalized respiratory status is defined as room air saturation of oxygen \[SaO2\] greater than or equal to 93% AND respiratory rate within normal ranges. |
| Duration of Supplemental Oxygen | Measured from Day 0 through Day 28 | Duration of supplemental oxygen use in days |
| Incidence of Acute Respiratory Distress Syndrome (ARDS) Present | Measured at Days 0, 1, 2, 4, 7, 14, 28 | Incidence of participants with acute respiratory distress syndrome (ARDS), restricted to those without ARDS at Day 0. |
| Days on Mechanical Ventilation | Measured from Day 0 through Day 28 | Time (in days) of mechanical ventilation use |
| Duration of Mechanical Ventilation | Measured from Day 0 through Day 28 | Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up. |
| Disposition Following Initial Hospitalization | Measured from Day 0 through Day 28 | Disposition following initial hospitalization was categorized as follows: released home - home health care not required, released home with home health care, transferred to long-term care facility, hospitalization ongoing at Day 28, deceased. |
| Duration of Viral Shedding < Lower Limit of Quantification (LLOQ) in Nasal Swabs | Measured from Day 0 through Day 28 | Duration of viral shedding \< lower limit of quantification (LLOQ) in nasal swabs (restricted to participants with viral shedding \>= LLOQ in nasal swabs at Day 0) |
| Incidence and Week of Gestation of Delivery of a Live Pre-term Infant for Pregnant Women | Measured through to Day 28 | Incidence and week of gestation of delivery of a live pre-term infant for pregnant female participants |
| Incidence and Duration of Pre-term Labor (Defined as Labor Occurring < 36 Weeks) for Pregnant Women | Measured through Day 28 | Incidence and duration of pre-term labor (defined as labor occurring \< 36 weeks) for pregnant female participants |
| Incidence of Spontaneous Abortion or Stillborn Fetus for Pregnant Women | Measured from Day 0 through Day 28 | Incidence of spontaneous abortion or stillborn fetus for pregnant female participants |
| Days on Supplemental Oxygen | Measured from Day 0 through Day 28 | Time (in days) of supplemental oxygen use |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Plasma and Standard Care Participants will receive plasma with high titer anti-influenza A or anti-influenza B antibodies in addition to standard care.
Anti-Influenza Immune Plasma: 2 units of plasma with high titer anti-influenza A or anti-influenza B antibodies at baseline
Standard Care: Standard care for hospitalized people with influenza | 49 |
| Standard Care Participants will receive standard care.
Standard Care: Standard care for hospitalized people with influenza | 49 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 5 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 7 |
Baseline characteristics
| Characteristic | Plasma and Standard Care | Standard Care | Total |
|---|---|---|---|
| Age, Continuous | 50 years | 57 years | 53 years |
| Age, Customized <18 | 4 Participants | 7 Participants | 11 Participants |
| Age, Customized >=18 | 45 Participants | 42 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 39 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 9 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) White | 29 Participants | 32 Participants | 61 Participants |
| Sex: Female, Male Female | 24 Participants | 27 Participants | 51 Participants |
| Sex: Female, Male Male | 25 Participants | 22 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 49 | 5 / 49 |
| other Total, other adverse events | 36 / 46 | 29 / 52 |
| serious Total, serious adverse events | 9 / 46 | 20 / 52 |
Outcome results
Primary
Time to Normalization of Respiratory Status (Primary Efficacy Population)
Normalized respiratory status is defined as room air saturation of oxygen \[SaO2\] greater than or equal to 93% AND respiratory rate within normal ranges.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Time to Normalization of Respiratory Status (Primary Efficacy Population) | 7 days |
| Standard Care | Time to Normalization of Respiratory Status (Primary Efficacy Population) | 28 days |
p-value: 0.069Log Rank
Secondary
28-day Mortality
Number of deaths during study follow-up
Time frame: Measured from Day 0 through Day 28
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plasma and Standard Care | 28-day Mortality | 1 participants |
| Standard Care | 28-day Mortality | 5 participants |
Secondary
50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time
Number of participants with ABG done and no increase of 50 millimeters of mercury (mm/Hg) or greater in PaO2/FiO2 ratio. PaO2/FiO2 ratio was evaluated by an ABG. ABG was performed only when clinically indicated.
Time frame: Measured at Days 1, 2, 4, 7, 14, 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza. This subset was further restricted to those participants with a PaO2/FiO2 ratio (ABG performed) at Day 0.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plasma and Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 7 | 7 participants |
| Plasma and Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 28 | 2 participants |
| Plasma and Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 4 | 7 participants |
| Plasma and Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 1 | 11 participants |
| Plasma and Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 14 | 3 participants |
| Plasma and Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 2 | 12 participants |
| Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 14 | 5 participants |
| Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 4 | 11 participants |
| Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 7 | 9 participants |
| Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 2 | 12 participants |
| Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 28 | 3 participants |
| Standard Care | 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time | Day 1 | 14 participants |
Secondary
Days on Mechanical Ventilation
Time (in days) of mechanical ventilation use
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Days on Mechanical Ventilation | 0 days |
| Standard Care | Days on Mechanical Ventilation | 3 days |
Secondary
Days on Supplemental Oxygen
Time (in days) of supplemental oxygen use
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Days on Supplemental Oxygen | 7 days |
| Standard Care | Days on Supplemental Oxygen | 8 days |
Secondary
Disposition Following Initial Hospitalization
Disposition following initial hospitalization was categorized as follows: released home - home health care not required, released home with home health care, transferred to long-term care facility, hospitalization ongoing at Day 28, deceased.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plasma and Standard Care | Disposition Following Initial Hospitalization | deceased | 1 participants |
| Plasma and Standard Care | Disposition Following Initial Hospitalization | released home - home health care not required | 21 participants |
| Plasma and Standard Care | Disposition Following Initial Hospitalization | released home with home health care | 9 participants |
| Plasma and Standard Care | Disposition Following Initial Hospitalization | transferred to long-term care facility | 4 participants |
| Plasma and Standard Care | Disposition Following Initial Hospitalization | hospitalization ongoing at Day 28 | 7 participants |
| Standard Care | Disposition Following Initial Hospitalization | hospitalization ongoing at Day 28 | 9 participants |
| Standard Care | Disposition Following Initial Hospitalization | transferred to long-term care facility | 6 participants |
| Standard Care | Disposition Following Initial Hospitalization | released home - home health care not required | 17 participants |
| Standard Care | Disposition Following Initial Hospitalization | deceased | 5 participants |
| Standard Care | Disposition Following Initial Hospitalization | released home with home health care | 6 participants |
Secondary
Duration of Hospitalization
Days that a participant spent at the hospital. Multiple hospitalizations are summed up.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Hospitalization | 6 days |
| Standard Care | Duration of Hospitalization | 11 days |
Secondary
Duration of Mechanical Ventilation
Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Mechanical Ventilation | 0 days |
| Standard Care | Duration of Mechanical Ventilation | 3 days |
Secondary
Duration of Stay in ICU
Days that a participant spent in ICU. Multiple ICU admissions are summed up.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Stay in ICU | 2.5 days |
| Standard Care | Duration of Stay in ICU | 3 days |
Secondary
Duration of Supplemental Oxygen
Duration of supplemental oxygen use in days
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Supplemental Oxygen | 7 days |
| Standard Care | Duration of Supplemental Oxygen | 8 days |
Secondary
Duration of Time to Resolution of All Symptoms and Fever
The assessed symptoms were nausea, vomiting, diarrhea, sore throat, headache, muscle ache, cough, and shortness of breath. Fever was defined as either a temperature \> 38.0 C, or a report of a Grade 1 or higher fever as an adverse event.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Time to Resolution of All Symptoms and Fever | NA days |
| Standard Care | Duration of Time to Resolution of All Symptoms and Fever | NA days |
Secondary
Duration of Time to Resolution of Clinical Symptoms
The assessed clinical symptoms were nausea, vomiting, diarrhea, sore throat, headache, muscle ache, cough, and shortness of breath. Symptoms were assessed at days 0, 1, 2, 4, 7, 14, and 28.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Time to Resolution of Clinical Symptoms | NA days |
| Standard Care | Duration of Time to Resolution of Clinical Symptoms | NA days |
Secondary
Duration of Time to Resolution of Fever
Fever was defined as either a temperature \> 38.0 C, or a report of a Grade 1 or higher fever as an adverse event.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Time to Resolution of Fever | NA days |
| Standard Care | Duration of Time to Resolution of Fever | NA days |
Secondary
Duration of Viral Shedding < Lower Limit of Quantification (LLOQ) in Nasal Swabs
Duration of viral shedding \< lower limit of quantification (LLOQ) in nasal swabs (restricted to participants with viral shedding \>= LLOQ in nasal swabs at Day 0)
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza. This subset was further restricted to those participants with viral shedding \>= LLOQ in nasal swabs at Day 0.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Duration of Viral Shedding < Lower Limit of Quantification (LLOQ) in Nasal Swabs | 1 days |
| Standard Care | Duration of Viral Shedding < Lower Limit of Quantification (LLOQ) in Nasal Swabs | 1 days |
Secondary
Incidence and Duration of Pre-term Labor (Defined as Labor Occurring < 36 Weeks) for Pregnant Women
Incidence and duration of pre-term labor (defined as labor occurring \< 36 weeks) for pregnant female participants
Time frame: Measured through Day 28
Population: Measure was not analyzed since there was only one pregnant participant. No aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Secondary
Incidence and Week of Gestation of Delivery of a Live Pre-term Infant for Pregnant Women
Incidence and week of gestation of delivery of a live pre-term infant for pregnant female participants
Time frame: Measured through to Day 28
Population: Measure was not analyzed since there was only one pregnant participant. No aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Secondary
Incidence of Acute Respiratory Distress Syndrome (ARDS) Present
Incidence of participants with acute respiratory distress syndrome (ARDS), restricted to those without ARDS at Day 0.
Time frame: Measured at Days 0, 1, 2, 4, 7, 14, 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza. This population is further restricted to those participants who did not have ARDS at Day 0.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plasma and Standard Care | Incidence of Acute Respiratory Distress Syndrome (ARDS) Present | 0 participants |
| Standard Care | Incidence of Acute Respiratory Distress Syndrome (ARDS) Present | 3 participants |
Secondary
Incidence of Spontaneous Abortion or Stillborn Fetus for Pregnant Women
Incidence of spontaneous abortion or stillborn fetus for pregnant female participants
Time frame: Measured from Day 0 through Day 28
Population: Measure was not analyzed since there was only one pregnant participant. No aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Secondary
In-hospital Mortality
Number of deaths in hospital during initial hospital admission
Time frame: Measured from Day 0 through Day 28
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plasma and Standard Care | In-hospital Mortality | 1 participants |
| Standard Care | In-hospital Mortality | 5 participants |
Secondary
Number of ICU Admissions
Number of ICU admissions during study follow-up. The intent was to analyze any number of ICU admissions.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plasma and Standard Care | Number of ICU Admissions | 1 ICU admission | 40 participants |
| Plasma and Standard Care | Number of ICU Admissions | 2 ICU admissions | 2 participants |
| Plasma and Standard Care | Number of ICU Admissions | 4 ICU admissions | 0 participants |
| Standard Care | Number of ICU Admissions | 1 ICU admission | 38 participants |
| Standard Care | Number of ICU Admissions | 2 ICU admissions | 5 participants |
| Standard Care | Number of ICU Admissions | 4 ICU admissions | 2 participants |
Secondary
Time to 20% Improvement in Sequential Organ Failure Assessment (SOFA) Score for Participants >= 18 Years Old and Pediatric Logistic Organ Dysfunction (PELOD) Score for Participants < 18 Years Old
The analysis is restricted to participants \>= 18 years old and the SOFA score because there were very few evaluations of the PELOD score during follow-up for the participants \< 18 years old. The adult population was further subset to those with a non-missing and non-zero SOFA score at Day 0; those with missing SOFA score at Day 0 did not have a starting point, and those with SOFA = 0 at Day 0 could not have an improvement.
Time frame: Measured from Day 0 through Day 28
Population: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza. This subset was further restricted to those \>= 18 years with an available (non-zero) Day 0 SOFA evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Time to 20% Improvement in Sequential Organ Failure Assessment (SOFA) Score for Participants >= 18 Years Old and Pediatric Logistic Organ Dysfunction (PELOD) Score for Participants < 18 Years Old | 4 days |
| Standard Care | Time to 20% Improvement in Sequential Organ Failure Assessment (SOFA) Score for Participants >= 18 Years Old and Pediatric Logistic Organ Dysfunction (PELOD) Score for Participants < 18 Years Old | 28 days |
Secondary
Time to Normalization of Respiratory Status (All Randomized Participants)
Normalized respiratory status is defined as room air saturation of oxygen \[SaO2\] greater than or equal to 93% AND respiratory rate within normal ranges.
Time frame: Measured from Day 0 through Day 28
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma and Standard Care | Time to Normalization of Respiratory Status (All Randomized Participants) | 14 days |
| Standard Care | Time to Normalization of Respiratory Status (All Randomized Participants) | NA days |