Influenza A Virus InfectionPhase 3NCT02572817

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

A Phase 3 study testing High-titer anti-influenza plasma and Low-titer anti-influenza plasma in people with Influenza A Virus Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 30 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 2 weeks and older
Conditions the study is for: Influenza A Virus Infection
What is being tested?: High-titer anti-influenza plasma and Low-titer anti-influenza plasma
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 138 participants
Where: 30 sitesUnited States
Study dates: Nov 2015to 18 May 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 weeks and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Show all 12Show fewer

Willingness to return for all required study visits and participate in study follow up.
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.

Who cannot join

Strong clinical evidence in the judgment of the site investigator that the etiology of illness is primarily bacterial super-infection in origin. Co-infection would be allowed, as there may be benefit to resolving influenza illness faster. Super-infection, where influenza illness occurred and is resolving, and new bacterial illness causing deterioration should be excluded (e.g., if the subject's respiratory infection is thought unlikely to benefit from additional antiviral therapy, this exclusion criteria would be met).
Prior treatment with any anti-influenza investigational drug, anti-influenza investigational intravenous immune globulin (IVIG), or anti-influenza investigational plasma therapy within 30 days prior to screening. Other investigational drug therapies (non-influenza) and administration of plasma and/or IVIG for non-influenza reasons are allowed.
History of allergic reaction to blood or plasma products (as judged by the site investigator).
A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy). Prior IVIG use alone would not meet exclusion criteria, but the investigator should consider the potential for a hyper-coagulable state.
Subjects who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol, including being not contactable following discharge from hospital.
Medical conditions for which receipt of 500-600 mL (or pediatric equivalent) of intravenous fluid may be dangerous to the subject (e.g., decompensated congestive heart failure).

Trial locations and contacts

30 sites in 1 country.

City, postcode or hospital

30 sites in 1 country

United States30 sites

University of Michigan
Ann Arbor, Michigan, 48109
Children's Hospital Colorado
Aurora, Colorado, 80045
University of Colorado Denver
Aurora, Colorado, 80045
University of Maryland Medical Center
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 021141
Boston Children's Hospital
Boston, Massachusetts, 02115
Bridgeport Hospital
Bridgeport, Connecticut, 06610
University of Vermont
Burlington, Vermont, 05405
Carolinas Medical Center
Charlotte, North Carolina, 28207
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Cincinnati
Cincinnati, Ohio, 45267
UT Southwestern Medical Center
Dallas, Texas, 75235
Duke University
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32608
UCLA Pediatrics Infectious Diseases
Los Angeles, California, 90095-1752
New York University/Bellevue Hospital
New York, New York, 10016
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Creighton University Medical Center
Omaha, Nebraska, 68124
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Mayo Clinic Campus Saint Mary's
Rochester, Minnesota, 55905
Beaumont Hospital - Royal Oak
Royal Oak, Michigan, 48073
Naval Medical Center San Diego (NMCSD)
San Diego, California, 92134
St. Louis Children's Hospital at Washington University
St Louis, Missouri, 63110
Madigan Army Medical Center (MAMC)
Tacoma, Washington, 98431
Beaumont Hospital, Troy
Troy, Michigan, 48085
University of Arizona Health Sciences Center
Tucson, Arizona, 85724
University of Massachusetts Medical School
Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: A Randomized Double-Blind, Phase 3 Study Comparing the Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Treatment of Severe Influenza A

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.

Read the 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.

Conditions: Influenza A Virus Infection
Being tested: High-titer anti-influenza plasma, Low-titer anti-influenza plasma
Keywords: Anti-Influenza Immune Plasma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

High-titer anti-influenza plasmaBiological
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
Low-titer anti-influenza plasmaBiological
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

Study groups in NCT02572817
Study group	Role	What they receive
High-titer anti-influenza plasma	Experimental	Participants received two intravenous infusions of high-titer anti-influenza plasma on Study Day 0. Receives: Biological: High-titer anti-influenza plasma
Low-titer anti-influenza plasma	Active comparator	Participants received two intravenous infusions of low-titer anti-influenza plasma on Study Day 0. Receives: Biological: Low-titer anti-influenza plasma

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Day 7

Secondary outcomes (29)

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
Measured: Day 1
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
Measured: Day 2
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
Measured: Day 3
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
Measured: Day 14
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
Measured: Day 28
Duration of Initial Hospitalization
Duration (in days) of initial hospitalization, restricted to duration between randomization and last visit
Measured: From Day 0 to Day 28
28-day Mortality
Number of deaths during study follow-up
Measured: From Day 0 to Day 28
In-hospital Mortality During Initial Hospitalization
Number of deaths in the hospital during initial hospitalization
Measured: From Day 0 to Day 28
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
Measured: Day 7, Day 14, Day 28
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.
Measured: Day 0, Day 3, Day 7
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.
Measured: Day 0, Day 3, Day 7
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.
Measured: From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry.
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
Measured: From Day 0 to Day 28
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.
Measured: From Day 0 to Day 28
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
Measured: From Day 0 to Day 28
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.
Measured: From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry
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
Measured: From Day 0 to Day 28
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.
Measured: From Day 0 to Day 28
Incidence of New ARDS During the Study
Incidence of new ARDS during the study among those participants without ARDS at randomization
Measured: From Day 0 to Day 28
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.
Measured: From Day 0 to Day 28
Incidence of New ECMO Use During the Study
Incidence of new ECMO use during the study among those participants not on ECMO at randomization
Measured: From Day 0 to Day 28
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.
Measured: Day 0, Day 3, Day 7
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.
Measured: Day 0, Day 3, Day 7
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.
Measured: From Day 0 to Day 28
Detectable Influenza Virus at Day 3
Detectable influenza virus at Day 3 in oropharyngeal samples
Measured: Day 3
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.
Measured: Day 1, Day 3, Day 7
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.
Measured: Day 1, Day 3, Day 7
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.
Measured: From Day 0 to Day 28
Number of Participants With Serious Adverse Events (SAEs).
Number of participants with reported serious adverse events (SAEs) throughout the study duration.
Measured: From Day 0 to Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 201518 May 2018

First posted9 Oct 2015 (estimated)
Study startNov 2015
Primary completion26 Apr 2018
Study completion18 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Influenza A Virus InfectionStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 138 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02572817
Sponsor's protocol ID: IRC-005
Status last verified: Jun 2019
First submitted: 7 Oct 2015
Last updated: 25 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998 Nov;26(11):1793-800. doi: 10.1097/00003246-199811000-00016.
PubMed 9824069
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. No abstract available.
PubMed 8844239
Leteurtre S, Duhamel A, Grandbastien B, Lacroix J, Leclerc F. Paediatric logistic organ dysfunction (PELOD) score. Lancet. 2006 Mar 18;367(9514):897; author reply 900-2. doi: 10.1016/S0140-6736(06)68371-2. No abstract available.
PubMed 16546531
Leteurtre S, Martinot A, Duhamel A, Proulx F, Grandbastien B, Cotting J, Gottesman R, Joffe A, Pfenninger J, Hubert P, Lacroix J, Leclerc F. Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet. 2003 Jul 19;362(9379):192-7. doi: 10.1016/S0140-6736(03)13908-6.
PubMed 12885479
Smith GB, Prytherch DR, Meredith P, Schmidt PE, Featherstone PI. The ability of the National Early Warning Score (NEWS) to discriminate patients at risk of early cardiac arrest, unanticipated intensive care unit admission, and death. Resuscitation. 2013 Apr;84(4):465-70. doi: 10.1016/j.resuscitation.2012.12.016. Epub 2013 Jan 4.
PubMed 23295778
Parshuram CS, Bayliss A, Reimer J, Middaugh K, Blanchard N. Implementing the Bedside Paediatric Early Warning System in a community hospital: A prospective observational study. Paediatr Child Health. 2011 Mar;16(3):e18-22. doi: 10.1093/pch/16.3.e18.
PubMed 22379384
Beigel JH, Aga E, Elie-Turenne MC, Cho J, Tebas P, Clark CL, Metcalf JP, Ozment C, Raviprakash K, Beeler J, Holley HP Jr, Warner S, Chorley C, Lane HC, Hughes MD, Davey RT Jr; IRC005 Study Team. Anti-influenza immune plasma for the treatment of patients with severe influenza A: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2019 Nov;7(11):941-950. doi: 10.1016/S2213-2600(19)30199-7. Epub 2019 Sep 30.
PubMed 31582360

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Healthy Participants

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Study at a glance

From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Double-Blind, Phase 3 Study Comparing the Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Treatment of Severe Influenza A
ClinicalTrials.gov ID: NCT02572817
Acronym / sponsor ID: IRC-005
Conditions: Influenza A Virus Infection
Keywords: Anti-Influenza Immune Plasma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 138 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: Nov 2015
Primary completion: 26 Apr 2018 (actual)
Study completion: 18 May 2018 (actual)
First posted: 9 Oct 2015 (estimated)
Results: Posted 14 Jun 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
High-titer anti-influenza plasma	Experimental	Biological: High-titer anti-influenza plasmaParticipants received two intravenous infusions of high-titer anti-influenza plasma on Study Day 0.
Low-titer anti-influenza plasma	Active comparator	Biological: Low-titer anti-influenza plasmaParticipants received two intravenous infusions of low-titer anti-influenza plasma on Study Day 0.

Who may qualify

Ages: 2 weeks and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (12 listed)

Subjects must be aged 2 weeks or older.
Hospitalization due to signs and symptoms of influenza.
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.

Key exclusion criteria (6 listed)

Strong clinical evidence in the judgment of the site investigator that the etiology of illness is primarily bacterial super-infection in origin. Co-infection would be allowed, as there may be benefit to resolving influenza illness faster. Super-infection, where influenza illness occurred and is resolving, and new bacterial illness causing deterioration should be excluded (e.g., if the subject's respiratory infection is thought unlikely to benefit from additional antiviral therapy, this exclusion criteria would be met).
Prior treatment with any anti-influenza investigational drug, anti-influenza investigational intravenous immune globulin (IVIG), or anti-influenza investigational plasma therapy within 30 days prior to screening. Other investigational drug therapies (non-influenza) and administration of plasma and/or IVIG for non-influenza reasons are allowed.
History of allergic reaction to blood or plasma products (as judged by the site investigator).
A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy). Prior IVIG use alone would not meet exclusion criteria, but the investigator should consider the potential for a hyper-coagulable state.
Subjects who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol, including being not contactable following discharge from hospital.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
High-titer anti-influenza plasmaHuman 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	Biological	High-titer anti-influenza plasma
Low-titer anti-influenza plasmaHuman 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	Biological	Low-titer anti-influenza plasma

Primary outcome

Clinical Status at Day 7
Time frame: 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

29 secondary outcomes

Clinical Status at Day 1
Time frame: Day 1
Clinical Status at Day 2
Time frame: Day 2
Clinical Status at Day 3
Time frame: Day 3
Clinical Status at Day 14
Time frame: Day 14
Clinical Status at Day 28
Time frame: Day 28
Duration of Initial Hospitalization
Time frame: From Day 0 to Day 28
28-day Mortality
Time frame: From Day 0 to Day 28
In-hospital Mortality During Initial Hospitalization
Time frame: From Day 0 to Day 28
Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28
Time frame: Day 7, Day 14, Day 28
Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score
Time frame: Day 0, Day 3, Day 7
Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score
Time frame: Day 0, Day 3, Day 7
Duration of Supplemental Oxygen
Time frame: From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry.
Incidence of New Oxygen Use During the Study
Time frame: From Day 0 to Day 28
Duration of Intensive Care Unit (ICU) Stay
Time frame: From Day 0 to Day 28
Incidence of New ICU Admission Use During the Study
Time frame: From Day 0 to Day 28
Duration of Mechanical Ventilation Use
Time frame: From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry
Incidence of New Mechanical Ventilation Use Stay Use During the Study
Time frame: From Day 0 to Day 28
Duration of Acute Respiratory Distress Syndrome (ARDS)
Time frame: From Day 0 to Day 28
Incidence of New ARDS During the Study
Time frame: From Day 0 to Day 28
Duration of Extracorporeal Membrane Oxygenation (ECMO)
Time frame: From Day 0 to Day 28
Incidence of New ECMO Use During the Study
Time frame: From Day 0 to Day 28
Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score
Time frame: Day 0, Day 3, Day 7
Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score
Time frame: Day 0, Day 3, Day 7
Disposition After Initial Hospitalization
Time frame: From Day 0 to Day 28
Detectable Influenza Virus at Day 3
Time frame: Day 3
Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1
Time frame: Day 1, Day 3, Day 7
Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2
Time frame: Day 1, Day 3, Day 7
Number of Participants With Grade 3 and 4 Adverse Events (AEs).
Time frame: From Day 0 to Day 28
Number of Participants With Serious Adverse Events (SAEs).
Time frame: From Day 0 to Day 28

Results and safety

Results posted to the registry on 14 Jun 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
High-titer Anti-influenza Plasma mITT	91	82
Low-titer Anti-influenza Plasma mITT	47	41

Primary outcome: Clinical Status at Day 7

Time frame: Day 7. Count of participants. Unit: Participants

Measure	High-titer Anti-influenza Plasma mITT n = 91	Low-titer Anti-influenza Plasma mITT n = 46
Death	2	2
in ICU	15	10
Non-ICU hospitalization with supplemental O2	16	7
Non-ICU hospitalization without supplemental O2	8	5
Not hospitalized, unable for normal activity	30	11
Not hospitalized, able for normal activity	20	11

High-titer Anti-influenza Plasma mITT vs Low-titer Anti-influenza Plasma mITT: Odds Ratio (OR): 1.22 (95% CI 0.65 to 2.29), p = 0.54, Regression, Logistic

Population analysed: Modified intent-to-treat population: subgroup of randomized participants who received any study treatment (with available data).

29 secondary outcomes are reported in the full results.

Adverse events

Time frame: From study entry (Day 0) to Day 28. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
High-titer Anti-influenza Plasma mITT	31 of 91 (34.1%)	0 of 91 (0%)	6 of 91
Low-titer Anti-influenza Plasma mITT	15 of 47 (31.9%)	0 of 47 (0%)	4 of 47

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 9824069Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998 Nov;26(11):1793-800. doi: 10.1097/00003246-199811000-00016.
Background: PubMed 8844239Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. No abstract available.
Background: PubMed 16546531Leteurtre S, Duhamel A, Grandbastien B, Lacroix J, Leclerc F. Paediatric logistic organ dysfunction (PELOD) score. Lancet. 2006 Mar 18;367(9514):897; author reply 900-2. doi: 10.1016/S0140-6736(06)68371-2. No abstract available.
Background: PubMed 12885479Leteurtre S, Martinot A, Duhamel A, Proulx F, Grandbastien B, Cotting J, Gottesman R, Joffe A, Pfenninger J, Hubert P, Lacroix J, Leclerc F. Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet. 2003 Jul 19;362(9379):192-7. doi: 10.1016/S0140-6736(03)13908-6.
Background: PubMed 23295778Smith GB, Prytherch DR, Meredith P, Schmidt PE, Featherstone PI. The ability of the National Early Warning Score (NEWS) to discriminate patients at risk of early cardiac arrest, unanticipated intensive care unit admission, and death. Resuscitation. 2013 Apr;84(4):465-70. doi: 10.1016/j.resuscitation.2012.12.016. Epub 2013 Jan 4.
Background: PubMed 22379384Parshuram CS, Bayliss A, Reimer J, Middaugh K, Blanchard N. Implementing the Bedside Paediatric Early Warning System in a community hospital: A prospective observational study. Paediatr Child Health. 2011 Mar;16(3):e18-22. doi: 10.1093/pch/16.3.e18.
Derived from this study: PubMed 31582360Beigel JH, Aga E, Elie-Turenne MC, Cho J, Tebas P, Clark CL, Metcalf JP, Ozment C, Raviprakash K, Beeler J, Holley HP Jr, Warner S, Chorley C, Lane HC, Hughes MD, Davey RT Jr; IRC005 Study Team. Anti-influenza immune plasma for the treatment of patients with severe influenza A: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2019 Nov;7(11):941-950. doi: 10.1016/S2213-2600(19)30199-7. Epub 2019 Sep 30.

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Healthy Participants

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John Beigel, MD study chair

Leidos Biomedical Research, Inc. in support of Clinical Research Section, LIR, NIAID, National Institutes of Health

30 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Status at Day 7 (time frame: Day 7). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02572817, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2019.