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

NCT ID: NCT02572817

Last Updated: 2019-06-25

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2018-05-18

Brief Summary

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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

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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

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Influenza A Virus Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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High-titer anti-influenza plasma

Participants received two intravenous infusions of high-titer anti-influenza plasma on Study Day 0.

Group Type EXPERIMENTAL

High-titer anti-influenza plasma

Intervention Type BIOLOGICAL

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 plasma

Participants received two intravenous infusions of low-titer anti-influenza plasma on Study Day 0.

Group Type ACTIVE_COMPARATOR

Low-titer anti-influenza plasma

Intervention Type BIOLOGICAL

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

Interventions

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High-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

Intervention Type BIOLOGICAL

Low-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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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.


* 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

* 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).
* 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).
Minimum Eligible Age

2 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Beigel, MD

Role: STUDY_CHAIR

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

Locations

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University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

UCLA Pediatrics Infectious Diseases

Los Angeles, California, United States

Site Status

Naval Medical Center San Diego (NMCSD)

San Diego, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Bridgeport Hospital

Bridgeport, Connecticut, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Beaumont Hospital - Royal Oak

Royal Oak, Michigan, United States

Site Status

Beaumont Hospital, Troy

Troy, Michigan, United States

Site Status

Mayo Clinic Campus Saint Mary's

Rochester, Minnesota, United States

Site Status

St. Louis Children's Hospital at Washington University

St Louis, Missouri, United States

Site Status

Creighton University Medical Center

Omaha, Nebraska, United States

Site Status

New York University/Bellevue Hospital

New York, New York, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Vermont

Burlington, Vermont, United States

Site Status

Madigan Army Medical Center (MAMC)

Tacoma, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 9824069 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8844239 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16546531 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12885479 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23295778 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22379384 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31582360 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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IRC-005

Identifier Type: -

Identifier Source: org_study_id

NCT02610478

Identifier Type: -

Identifier Source: nct_alias

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