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Evaluating the Safety and Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults Hospitalized With Influenza

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ClinicalTrials.gov Identifier: NCT02287467
Recruitment Status : Completed
First Posted : November 10, 2014
Results First Posted : November 14, 2019
Last Update Posted : November 14, 2019
Sponsor:
Collaborators:
University of Minnesota
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
Influenza (the flu) is a common illness that usually occurs in autumn and winter. The flu is usually mild, but can cause serious illness or death. The purpose of this study is to test the safety and effectiveness of an antibody against the flu (called intravenous hyperimmune immunoglobulin or IVIG) in people who are hospitalized for severe flu.

Condition or disease Intervention/treatment Phase
Influenza A Influenza B Biological: Intravenous hyperimmune immunoglobulin (IVIG) Biological: Placebo for IVIG Phase 3

Detailed Description:

Influenza is responsible for thousands of hospitalizations and deaths each year in the United States and worldwide. One possible new treatment for the flu involves the use of IVIG, a blood product containing antibodies from people who have recovered from the flu or who have had a flu shot. The purpose of this study is to evaluate whether IVIG can reduce the severity and duration of flu in people who are hospitalized with the flu.

The study will enroll participants 18 years and older who are hospitalized with the flu. The study will enroll participants over one or more flu seasons. Regardless of the date of enrollment, each participant will be in the study for about 28 days.

At study entry (Day 0), participants will be randomly assigned to one of two groups (Arms A and B). Participants in both groups will receive standard of care (SOC) treatment for the flu, but those in Arm A will also receive one dose of IVIG and those in Arm B will receive a placebo for IVIG. Both IVIG and placebo will be given intravenously over at least 2 hours.

On Day 0, before receiving IVIG or placebo, participants will undergo a symptoms assessment, blood collection, and a nasopharyngeal (NP) swab to collect a sample of secretions from the nose and throat.

Additional study visits will occur on Days 1, 2, 3, 7, 14, and 28. Depending on the visit, participants may take part in the same study procedures that took place on Day 0. On Days 2, 14, and 28, visits for participants who are no longer hospitalized may be conducted over the phone.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 329 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Anti-Influenza Hyperimmune Intravenous Immunoglobulin Clinical Outcome Study (INSIGHT 006: FLU-IVIG)
Study Start Date : January 2015
Actual Primary Completion Date : June 7, 2018
Actual Study Completion Date : June 7, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: Arm A: hIVIG
Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
Biological: Intravenous hyperimmune immunoglobulin (IVIG)
Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)

Placebo Comparator: Arm B: Placebo
Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
Biological: Placebo for IVIG
Administered IV as 500 mL of normal saline




Primary Outcome Measures :
  1. Number of Patients in Each of 6 Clinical Status Categories on Day 7 [ Time Frame: Assessed on Day 7 ]
    This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).


Secondary Outcome Measures :
  1. Number of Patients in Each of 5 Clinical Status Categories on Day 3 [ Time Frame: Assessed on Day 3 ]
    5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).

  2. Number of Patients in Each of 6 Clinical Status Categories on Day 3 [ Time Frame: Measured on Day 3 ]
    6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best).

  3. Number of Patients With a Favorable Outcome on Day 7 [ Time Frame: Assessed on Day 7 ]
    Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward.

  4. Hospital Discharge [ Time Frame: Measured through Day 7 ]
    Number of participants alive and discharged from the hospital

  5. Mortality [ Time Frame: Measured through day 28 ]
    Number of participants dying through day 28.

  6. Number of Patients Alive and Out of Hospital [ Time Frame: Measured through Day 28 ]
    Number and percent alive and out of hospital on day 28

  7. Change in Viral Load [ Time Frame: Day 3 ]
    Change in nasopharyngeal viral load from baseline to day 3

  8. Death or Re-hospitalization [ Time Frame: Day 28 ]
    Number and percent of participants who died or were re-hospitalized after initial discharge

  9. Percent of Participants Developing Complications [ Time Frame: Measured through Day 28 ]
    Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis

  10. Number of Patients in Each of 6 Clinical Status Categories on Day 14 [ Time Frame: Measured on day 14 ]
    6-category ordinal outcome measured on day 14

  11. Number of Patients Alive and Out of Hospital on Day 14 [ Time Frame: day 14 ]
    Number and percentage of participants alive and out of the hospital on Day 14

  12. Resumption of Normal Activities by Day 14 [ Time Frame: day 14 ]
    Participants reporting resumption of normal daily activities by Day 14

  13. Number of Patients in Each of 6 Clinical Status Categories on Day 28 [ Time Frame: day 28 ]
    6-category ordinal outcome corresponding to clinical status on day 28

  14. Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 [ Time Frame: Day 7 ]
    Primary 6-category ordinal outcome for participants infected with Influenza A

  15. Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 [ Time Frame: Day 7 ]
    Primary 6-category ordinal outcome for subgroup of participants infected with influenza B

  16. pH1N1 Titers at Day 7 [ Time Frame: Day 7 ]
    pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus

  17. H3N2 Titers at Day 7 [ Time Frame: Day 7 ]
    H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus

  18. Influenza B Titers at Day 7 [ Time Frame: Day 7 ]
    Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Locally determined positive influenza test (by polymerase chain reaction [PCR] or other nucleic acid test, or by rapid antigen [Ag]) from a specimen obtained within 2 days prior to randomization
  • Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever
  • Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
  • For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study
  • Willingness to have blood and respiratory samples obtained and stored
  • NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)

Exclusion Criteria:

  • Women who are pregnant or breast-feeding
  • Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin
  • Prior treatment with any investigational drug therapy within 30 days prior to screening
  • History of allergic reaction to blood or plasma products (as judged by the site investigator)
  • Known immunoglobulin A (IgA) deficiency
  • A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the participant at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy)
  • Presence of any pre-existing illness that, in the opinion of the site investigator, would place the participant at an unreasonably increased risk through participation in this study
  • Participants who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol
  • Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the participant (e.g., decompensated congestive heart failure)
  • Receiving extracorporeal membrane oxygenation (ECMO)
  • Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)

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): NCT02287467


  Show 21 Study Locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
University of Minnesota
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
Investigators
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Study Chair: Richard T. Davey, Jr., MD National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Eduardo Fernández-Cruz, MD, PhD Hospital General Universitario Gregorio Marañón
Study Chair: Norman P. Markowitz, MD The Henry Ford Hospital
Study Chair: Sarah L. Pett, MD, MBBS, DTM, MRCP (UK) University College, London
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Statistical Analysis Plan  [PDF] August 17, 2018
Study Protocol  [PDF] May 31, 2016


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02287467     History of Changes
Other Study ID Numbers: INSIGHT 006: FLU-IVIG
First Posted: November 10, 2014    Key Record Dates
Results First Posted: November 14, 2019
Last Update Posted: November 14, 2019
Last Verified: November 2019
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Antiviral
IVIG
Hemagglutination inhibition (HAI)
Antibody
Additional relevant MeSH terms:
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Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
gamma-Globulins
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs