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

NCT02572817 | Completed Phase 3 Results DMC

• 1 other identifier: IRC-005
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 30

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.

Conditions

Influenza A Virus Infection

Keywords

Anti-Influenza Immune Plasma

Outcome Measures

Primary Outcomes (1)

• 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

  Day 7

Secondary Outcomes (29)

• Clinical Status at Day 1

  Day 1

• Clinical Status at Day 2

  Day 2

• Clinical Status at Day 3

  Day 3

• Clinical Status at Day 14

  Day 14

• Clinical Status at Day 28

  Day 28

Study Arms (2)

High-titer anti-influenza plasma

EXPERIMENTAL

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

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.

Biological: Low-titer anti-influenza plasma

Interventions

High-titer anti-influenza plasma 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

High-titer anti-influenza plasma

Low-titer anti-influenza plasma 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

Low-titer anti-influenza plasma

Eligibility Criteria

• Age: 2 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (30)

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

UCLA Pediatrics Infectious Diseases

Los Angeles, California, 90095-1752, United States

Location

Naval Medical Center San Diego (NMCSD)

San Diego, California, 92134, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Bridgeport Hospital

Bridgeport, Connecticut, 06610, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 021141, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Beaumont Hospital - Royal Oak

Royal Oak, Michigan, 48073, United States

Location

Beaumont Hospital, Troy

Troy, Michigan, 48085, United States

Location

Mayo Clinic Campus Saint Mary's

Rochester, Minnesota, 55905, United States

Location

St. Louis Children's Hospital at Washington University

St Louis, Missouri, 63110, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68124, United States

Location

New York University/Bellevue Hospital

New York, New York, 10016, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28207, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

University of Vermont

Burlington, Vermont, 05405, United States

Location

Madigan Army Medical Center (MAMC)

Tacoma, Washington, 98431, United States

Location

Related Publications (7)

• 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.

  PMID: 9824069 BACKGROUND

• 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.

  PMID: 8844239 BACKGROUND

• 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.

  PMID: 16546531 BACKGROUND

• 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.

  PMID: 12885479 BACKGROUND

• 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.

  PMID: 23295778 BACKGROUND

• 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.

  PMID: 22379384 BACKGROUND

• 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.

  PMID: 31582360 DERIVED

Results Point of Contact

• Title: John Beigel, M.D.
• Organization: National Institute of Allergy and Infectious Diseases (NIAID)

jbeigel@niaid.nih.gov

301-451-9881

Study Officials

• John Beigel, MD

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 9, 2015
• Study Start: November 1, 2015
• Primary Completion: April 26, 2018
• Study Completion: May 18, 2018
• Last Updated: June 25, 2019
• Results First Posted: June 14, 2019

Record last verified: 2019-06

Locations

US (30)