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

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ClinicalTrials.gov Identifier: NCT02572817
Recruitment Status : Recruiting
First Posted : October 9, 2015
Last Update Posted : May 25, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This study will assess 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.

Condition or disease Intervention/treatment Phase
Influenza A Virus Infection Biological: High-titer anti-influenza plasma Biological: Low-titer (control) anti-influenza plasma Phase 3

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 will enroll people aged 2 weeks or older who are hospitalized with severe influenza A infection. Participants will be randomly assigned to receive either high-titer anti-influenza plasma or low-titer (control) anti-influenza plasma on Day 0. In addition, all participants will receive standard care antivirals. Participants will be assessed on Day 0 (baseline) and on Days 1, 2, 3, 7, 14, and 28. For participants who are not hospitalized on Days 2, 14, and 28, researchers may contact participants by telephone. Study procedures will include clinical assessments, blood collection, and oropharyngeal swabs.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : November 2015
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: High-titer anti-influenza plasma
Participants will receive two intravenous infusions of high-titer anti-influenza plasma on Study Day 0.
Biological: 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

Active Comparator: Low-titer (control) anti-influenza plasma
Participants will receive two intravenous infusions of low-titer anti-influenza plasma on Study Day 0.
Biological: Low-titer (control) 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




Primary Outcome Measures :
  1. Subjects clinical status at Day 7 (6-point ordinal scale) [ Time Frame: Measured at Day 7 ]
    1. Death
    2. In ICU
    3. Non-ICU hospitalization, requiring supplemental oxygen
    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



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Enrollment (Screening):

  • 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.

Inclusion Criteria for Randomization:

  • 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 for Randomization:

  • 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 uncontactable 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02572817


Contacts
Contact: DCR Flu Operations DCRFluOperations@s-3.com

  Show 41 Study Locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: John Beigel, MD Leidos Biomedical Research, Inc. in support of Clinical Research Section, LIR, NIAID, National Institutes of Health

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02572817     History of Changes
Obsolete Identifiers: NCT02610478
Other Study ID Numbers: IRC-005
First Posted: October 9, 2015    Key Record Dates
Last Update Posted: May 25, 2018
Last Verified: May 2018

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Anti-Influenza Immune Plasma

Additional relevant MeSH terms:
Influenza, Human
Virus Diseases
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Infections
Respiratory Tract Diseases