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Trial record 1 of 1 for:    NCT01052480
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Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza (IRC002)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01052480
First received: January 16, 2010
Last updated: April 19, 2017
Last verified: April 2017
  Purpose
This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza A or B. Hospitalized subjects with influenza A or B that have either a low oxygen level or a high respiratory rate will be eligible for study participation. This study will enroll adults, children and pregnant women.

Condition Intervention Phase
Influenza A Influenza B Biological: Anti-Influenza Immune Plasma Drug: Standard Care Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Phase 2, Multicenter Safety and Exploratory Efficacy Study of Investigational Anti-Influenza Immune Plasma for the Treatment of Influenza (IRC002)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Time to Normalization of Respiratory Status (Primary Efficacy Population) [ Time Frame: Measured from Day 0 through Day 28 ]
    Normalized respiratory status is defined as room air saturation of oxygen [SaO2] greater than or equal to 93% AND respiratory rate within normal ranges.


Secondary Outcome Measures:
  • Time to Normalization of Respiratory Status (All Randomized Participants) [ Time Frame: Measured from Day 0 through Day 28 ]
    Normalized respiratory status is defined as room air saturation of oxygen [SaO2] greater than or equal to 93% AND respiratory rate within normal ranges.

  • Duration of Time to Resolution of Clinical Symptoms [ Time Frame: Measured from Day 0 through Day 28 ]
    The assessed clinical symptoms were nausea, vomiting, diarrhea, sore throat, headache, muscle ache, cough, and shortness of breath. Symptoms were assessed at days 0, 1, 2, 4, 7, 14, and 28.

  • Duration of Time to Resolution of Fever [ Time Frame: Measured from Day 0 through Day 28 ]
    Fever was defined as either a temperature > 38.0 C, or a report of a Grade 1 or higher fever as an adverse event.

  • Duration of Time to Resolution of All Symptoms and Fever [ Time Frame: Measured from Day 0 through Day 28 ]
    The assessed symptoms were nausea, vomiting, diarrhea, sore throat, headache, muscle ache, cough, and shortness of breath. Fever was defined as either a temperature > 38.0 C, or a report of a Grade 1 or higher fever as an adverse event.

  • Time to 20% Improvement in Sequential Organ Failure Assessment (SOFA) Score for Participants >= 18 Years Old and Pediatric Logistic Organ Dysfunction (PELOD) Score for Participants < 18 Years Old [ Time Frame: Measured from Day 0 through Day 28 ]
    The analysis is restricted to participants >= 18 years old and the SOFA score because there were very few evaluations of the PELOD score during follow-up for the participants < 18 years old. The adult population was further subset to those with a non-missing and non-zero SOFA score at Day 0; those with missing SOFA score at Day 0 did not have a starting point, and those with SOFA = 0 at Day 0 could not have an improvement.

  • 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time [ Time Frame: Measured at Days 1, 2, 4, 7, 14, 28 ]
    Number of participants with ABG done and no increase of 50 millimeters of mercury (mm/Hg) or greater in PaO2/FiO2 ratio. PaO2/FiO2 ratio was evaluated by an ABG. ABG was performed only when clinically indicated.

  • In-hospital Mortality [ Time Frame: Measured from Day 0 through Day 28 ]
    Number of deaths in hospital during initial hospital admission

  • 28-day Mortality [ Time Frame: Measured from Day 0 through Day 28 ]
    Number of deaths during study follow-up

  • Duration of Hospitalization [ Time Frame: Measured from Day 0 through Day 28 ]
    Days that a participant spent at the hospital. Multiple hospitalizations are summed up.

  • Number of ICU Admissions [ Time Frame: Measured from Day 0 through Day 28 ]
    Number of ICU admissions during study follow-up

  • Duration of Stay in ICU [ Time Frame: Measured from Day 0 through Day 28 ]
    Days that a participant spent in ICU. Multiple ICU admissions are summed up.

  • Days on Supplemental Oxygen [ Time Frame: Measured from Day 0 through Day 28 ]
    Time (in days) of supplemental oxygen use

  • Duration of Supplemental Oxygen [ Time Frame: Measured from Day 0 through Day 28 ]
    Duration of supplemental oxygen use in days

  • Incidence of Acute Respiratory Distress Syndrome (ARDS) Present [ Time Frame: Measured at Days 0, 1, 2, 4, 7, 14, 28 ]
    Incidence of participants with acute respiratory distress syndrome (ARDS), restricted to those without ARDS at Day 0.

  • Days on Mechanical Ventilation [ Time Frame: Measured from Day 0 through Day 28 ]
    Time (in days) of mechanical ventilation use

  • Duration of Mechanical Ventilation [ Time Frame: Measured from Day 0 through Day 28 ]
    Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up.

  • Disposition Following Initial Hospitalization [ Time Frame: Measured from Day 0 through Day 28 ]
    Disposition following initial hospitalization was categorized as follows: "released home - home health care not required", " released home with home health care", "transferred to long-term care facility", "hospitalization ongoing at Day 28", "deceased".

  • Duration of Viral Shedding < Lower Limit of Quantification (LLOQ) in Nasal Swabs [ Time Frame: Measured from Day 0 through Day 28 ]
    Duration of viral shedding < lower limit of quantification (LLOQ) in nasal swabs (restricted to participants with viral shedding >= LLOQ in nasal swabs at Day 0)

  • Incidence and Week of Gestation of Delivery of a Live Pre-term Infant for Pregnant Women [ Time Frame: Measured through to Day 28 ]
    Incidence and week of gestation of delivery of a live pre-term infant for pregnant female participants

  • Incidence and Duration of Pre-term Labor (Defined as Labor Occurring < 36 Weeks) for Pregnant Women [ Time Frame: Measured through Day 28 ]
    Incidence and duration of pre-term labor (defined as labor occurring < 36 weeks) for pregnant female participants

  • Incidence of Spontaneous Abortion or Stillborn Fetus for Pregnant Women [ Time Frame: Measured from Day 0 through Day 28 ]
    Incidence of spontaneous abortion or stillborn fetus for pregnant female participants


Enrollment: 98
Actual Study Start Date: December 2010
Study Completion Date: November 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plasma and Standard Care
Participants will receive plasma with high titer anti-influenza A or anti-influenza B antibodies (Anti-Influenza Immune Plasma) in addition to standard care.
Biological: Anti-Influenza Immune Plasma
2 units of plasma with high titer anti-influenza A or anti-influenza B antibodies at baseline
Drug: Standard Care
All subjects will receive an anti-influenza antiviral (e.g., oseltamivir or zanamivir), but may include treatment with licensed antivirals in patient populations or at doses not covered in the package insert, or with medications available under a EUA. Standard care may also include antibiotics and other medications.
Active Comparator: Standard Care
Participants will receive standard care.
Drug: Standard Care
All subjects will receive an anti-influenza antiviral (e.g., oseltamivir or zanamivir), but may include treatment with licensed antivirals in patient populations or at doses not covered in the package insert, or with medications available under a EUA. Standard care may also include antibiotics and other medications.

Detailed Description:

Morbidity and mortality occur despite treatment with current antivirals. Circulating influenza H1N1 and H3N2 isolates are highly resistant to amantadine and rimantadine, whereas previous seasonal H1N1 isolates were highly resistant to oseltamivir. So there is concern that circulating influenza A/H1N1 2009 virus may also acquire oseltamivir resistance.

This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza. Hospitalized subjects with influenza at risk for severe disease (as defined in the inclusion criteria) will be eligible for study participation. This study will enroll adults, children and pregnant women.

Up to 40 sites in the United States will participate in this protocol. One hundred eligible subjects will be randomized in a 1:1 ratio to receive either 2 units (or pediatric equivalent) of anti-influenza immune plasma on Study Day 0 in addition to standard care or standard care alone (50 subjects receiving standard care alone; 50 subjects receiving anti-influenza immune plasma and standard care).

Subjects will be assessed on Study Day 0 (pre-dose), 30 minutes post-dose (plasma arm only), and on Study Days 1, 2, 4, 7, 14, and 28. All subjects will undergo a series of efficacy, safety, and PK (HAI) assessments during the study. Blood samples will be collected at each time point (except Day 1). Nasal and oropharyngeal swabs for influenza PCR will be obtained on Days 0,1,2,4 and 7.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of influenza A or B within 72 hours prior to enrollment (by local assay including rapid antigen, direct fluorescent antibody (DFA), polymerase chain reaction (PCR), or culture, and must be able to detect and distinguish influenza A from influenza B)
  • Hospitalization for signs and symptoms of influenza (decision for hospitalization will be up to the individual treating clinician).
  • Abnormal respiratory status, defined as room air saturation of oxygen (SaO2) less than 93% or tachypnea (respiratory rate above an age adjusted normal range)
  • Agree to the storage of specimens and data
  • ABO compatible plasma available on site or available within 24 hours after randomization with activity against locally circulating strains of influenza

Exclusion Criteria:

  • Receipt of non-licensed treatment for influenza within the last 2 weeks (or plans to receive any time during the study). This does not include licensed drugs at non approved doses, off-label indications, or drugs available under an Emergency Use Authorization (EUA).
  • History of severe allergic reaction to blood products (as judged by the investigator).
  • Medical conditions for which receipt of 500 mL volume (or 8 mL/kg for pediatric patients) may be dangerous to the subject (e.g. decompensated congestive heart failure [CHF], etc.)
  • Clinical suspicion that etiology of acute illness is primarily due to a condition other than active influenza virus replication (e.g., a bacterial or fungal infection)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01052480

  Hide Study Locations
Locations
United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095-1752
Naval Medical Center San Diego
San Diego, California, United States, 92134
Los Angeles Biomedical Research Institute, CA
Torrance, California, United States, 90502
United States, District of Columbia
Children's National Medical Center
Washington, D.C., District of Columbia, United States, 20010
Washington, DC VA Med Center
Washington, D.C., District of Columbia, United States, 20422
United States, Florida
University of Florida
Gainesville, Florida, United States, 32608
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University (NU)
Chicago, Illinois, United States, 60611
The Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Maryland
University of Maryland School of Medicine Center for Vaccine Development
Baltimore, Maryland, United States, 21201
John Hopkins University (JHU)
Baltimore, Maryland, United States, 21218
Walter Reed National Military Medical Center (WRNMMC)
Bethesda, Maryland, United States, 20889
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital/Harvard Medical School
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Boston Med Center
Boston, Massachusetts, United States, 02118
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Bronson Healthcare Group
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
Saint Mary's Hospital (Mayo Clinic)
Rochester, Minnesota, United States, 55905
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
Cornell Clinical Trials Unit, New York Presbyterian Hospital, Weill Cornell Medical College
New York, New York, United States, 10065
Montefiore Medical Center/Albert Einstein College of Medicine
New York, New York, United States, 10467
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
University of Cincinnati College of Medicine
Cincinnati, Ohio, United States, 45267-0405
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Texas Tech University Health Science Center (HSC)- Amarillo
Amarillo, Texas, United States, 79106
Texas Children's Hospital
Houston, Texas, United States, 77030
Texas Tech HSC-Lubbock, TX
Lubbock, Texas, United States, 79430
United States, Virginia
Naval Medical Center Portsmouth
Portsmouth, Virginia, United States, 23708
United States, Washington
Madigan Army Medical Center (MAMC)
Tacoma, Washington, United States, 98431
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: John Beigel, MD Leidos Biomedical Research, Inc. in support of Laboratory of Immunoregulation, NIAID, NIH
Study Chair: Richard Davey, MD Laboratory of Immunoregulation, NIAID, NIH
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01052480     History of Changes
Other Study ID Numbers: 10-I-0043
IRC002 ( Other Identifier: NIAID Influenza Research Collaboration )
Study First Received: January 16, 2010
Results First Received: April 19, 2017
Last Updated: April 19, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Antiviral
Anti-Influenza Immune Plasma
Emerging Infectious Disease
Swine Flu

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

ClinicalTrials.gov processed this record on June 27, 2017