Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza
- Conditions
- Influenza AInfluenza B
- Interventions
- Biological: Anti-Influenza Immune PlasmaDrug: Standard Care
- Registration Number
- NCT01052480
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 98
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Plasma and Standard Care Anti-Influenza Immune Plasma Participants will receive plasma with high titer anti-influenza A or anti-influenza B antibodies (Anti-Influenza Immune Plasma) in addition to standard care. Plasma and Standard Care 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. Standard Care Standard Care Participants will receive standard care.
- Primary Outcome Measures
Name Time Method Time to Normalization of Respiratory Status (Primary Efficacy Population) 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
Name Time Method 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time 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.
Number of ICU Admissions Measured from Day 0 through Day 28 Number of ICU admissions during study follow-up. The intent was to analyze any number of ICU admissions.
Duration of Stay in ICU Measured from Day 0 through Day 28 Days that a participant spent in ICU. Multiple ICU admissions are summed up.
28-day Mortality Measured from Day 0 through Day 28 Number of deaths during study follow-up
Duration of Hospitalization Measured from Day 0 through Day 28 Days that a participant spent at the hospital. Multiple hospitalizations are summed up.
Time to Normalization of Respiratory Status (All Randomized Participants) 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 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 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 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 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.
In-hospital Mortality Measured from Day 0 through Day 28 Number of deaths in hospital during initial hospital admission
Days on Supplemental Oxygen Measured from Day 0 through Day 28 Time (in days) of supplemental oxygen use
Duration of Supplemental Oxygen Measured from Day 0 through Day 28 Duration of supplemental oxygen use in days
Incidence of Acute Respiratory Distress Syndrome (ARDS) Present 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 Measured from Day 0 through Day 28 Time (in days) of mechanical ventilation use
Duration of Mechanical Ventilation 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 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 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 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 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 Measured from Day 0 through Day 28 Incidence of spontaneous abortion or stillborn fetus for pregnant female participants
Trial Locations
- Locations (35)
University of Florida
🇺🇸Gainesville, Florida, United States
Los Angeles Biomedical Research Institute, CA
🇺🇸Torrance, California, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
John Hopkins University (JHU)
🇺🇸Baltimore, Maryland, United States
Bronson Healthcare Group
🇺🇸Kalamazoo, Michigan, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States
Northwestern University (NU)
🇺🇸Chicago, Illinois, United States
Texas Tech HSC-Lubbock, TX
🇺🇸Lubbock, Texas, United States
Walter Reed National Military Medical Center (WRNMMC)
🇺🇸Bethesda, Maryland, United States
Texas Tech University Health Science Center (HSC)- Amarillo
🇺🇸Amarillo, Texas, United States
Naval Medical Center Portsmouth
🇺🇸Portsmouth, Virginia, United States
Montefiore Medical Center/Albert Einstein College of Medicine
🇺🇸New York, New York, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center (UPMC)
🇺🇸Pittsburgh, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital/Harvard Medical School
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston Med Center
🇺🇸Boston, Massachusetts, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Children's National Medical Center
🇺🇸Washington, D.C., District of Columbia, United States
Naval Medical Center San Diego
🇺🇸San Diego, California, United States
Washington, DC VA Med Center
🇺🇸Washington, D.C., District of Columbia, United States
The Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Maryland School of Medicine Center for Vaccine Development
🇺🇸Baltimore, Maryland, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cornell Clinical Trials Unit, New York Presbyterian Hospital, Weill Cornell Medical College
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of Cincinnati College of Medicine
🇺🇸Cincinnati, Ohio, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Saint Mary's Hospital (Mayo Clinic)
🇺🇸Rochester, Minnesota, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Madigan Army Medical Center (MAMC)
🇺🇸Tacoma, Washington, United States