Comparing the Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Treatment of Severe Influenza A

Phase 3

Completed

Conditions: Influenza A Virus Infection

Interventions: Biological: High-titer anti-influenza plasma
Biological: Low-titer anti-influenza plasma

Registration Number: NCT02572817

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 138

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High-titer anti-influenza plasma	High-titer anti-influenza plasma	Participants received two intravenous infusions of high-titer anti-influenza plasma on Study Day 0.
Low-titer anti-influenza plasma	Low-titer anti-influenza plasma	Participants received two intravenous infusions of low-titer anti-influenza plasma on Study Day 0.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Duration of Initial Hospitalization	From Day 0 to Day 28	Duration (in days) of initial hospitalization, restricted to duration between randomization and last visit
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 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 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.
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.
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 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
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.
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
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
28-day Mortality	From Day 0 to Day 28	Number of deaths during study follow-up
In-hospital Mortality During Initial Hospitalization	From Day 0 to Day 28	Number of deaths in the hospital during initial hospitalization
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
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 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 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 ARDS During the Study	From Day 0 to Day 28	Incidence of new ARDS during the study among those participants without ARDS at randomization
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.
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.
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.
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.
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
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.
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.
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.
Detectable Influenza Virus at Day 3	Day 3	Detectable influenza virus at Day 3 in oropharyngeal samples

Trial Locations

Locations (30): Beaumont Hospital - Royal Oak
🇺🇸
Royal Oak, Michigan, United States
Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
UCLA Pediatrics Infectious Diseases
🇺🇸
Los Angeles, California, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
University of Colorado Denver
🇺🇸
Aurora, Colorado, United States
University of Maryland Medical Center
🇺🇸
Baltimore, Maryland, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
University of Massachusetts Medical School
🇺🇸
Worcester, Massachusetts, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Beaumont Hospital, Troy
🇺🇸
Troy, Michigan, United States
St. Louis Children's Hospital at Washington University
🇺🇸
Saint Louis, Missouri, United States
Creighton University Medical Center
🇺🇸
Omaha, Nebraska, United States
Mayo Clinic Campus Saint Mary's
🇺🇸
Rochester, Minnesota, United States
New York University/Bellevue Hospital
🇺🇸
New York, New York, United States
Carolinas Medical Center
🇺🇸
Charlotte, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Madigan Army Medical Center (MAMC)
🇺🇸
Tacoma, Washington, United States
Naval Medical Center San Diego (NMCSD)
🇺🇸
San Diego, California, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Duke University
🇺🇸
Durham, North Carolina, United States
University of Arizona Health Sciences Center
🇺🇸
Tucson, Arizona, United States
University of Vermont
🇺🇸
Burlington, Vermont, United States
Bridgeport Hospital
🇺🇸
Bridgeport, Connecticut, United States
University of Florida
🇺🇸
Gainesville, Florida, United States