• Time to normalization of respiratory status (defined as room air saturation of oxygen [SaO2] greater than or equal to 93% AND respiratory rate within normal ranges) [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  

• Duration of clinical symptoms, fever, intensive care unit (ICU) stay, and hospitalization [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Time to resolution of symptoms and fever [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Mortality [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Acute lung injury [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Acute respiratory distress syndrome (ARDS) [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Time to 20% improvement in sequential organ failure assessment (SOFA) score for participants at least 18 years old and pediatric logistic organ dysfunction (PELOD) score for those younger than 18 years old [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  
• Time to 50 millimeters of mercury (mm/Hg) improvement in partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  
• Incidence and duration of both supplemental oxygen use and mechanical ventilation use [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Disposition following initial hospitalization [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Birth complications for pregnant women [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Adverse events and laboratory abnormalities [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  
• Relationship between hemagglutination inhibition assay (HAI) and measures of viral clearance [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: No ]
  

Influenza A/H1N1 2009 (commonly referred to as "swine flu") is a novel influenza virus. Most people will not have immunity to it. H1N1 vaccines are available, but currently are in limited supply. As of October 17, 2009, worldwide there have been more than 414,000 laboratory confirmed cases of pandemic influenza H1N1 2009 and nearly 5,000 deaths reported to the World Health Organization (WHO). Initial reports suggested a high mortality rate (6% to 7%). Recent statistics suggest a mortality rate could be as high as 1.2% (5,000 deaths in 400,000 cases), although most countries are no longer collecting and reporting mild cases of H1N1. Mortality likely remains significantly higher than seasonal influenza.

Severe morbidity and mortality occur despite treatment with current antivirals. Additionally, circulating H1N1 isolates are highly resistant to amantadine and rimantadine, so there is concern this virus may also acquire oseltamivir resistance that is seen in circulating seasonal H1N1 virus.

This randomized, open label, multi-center, Phase 2 trial will assess the safety, efficacy, and pharmacokinetics of H1N1 plasma in participants with H1N1 influenza. Hospitalized participants with influenza A at risk of severe disease (as defined in the inclusion criteria) will be eligible for study participation. In addition to adults, this study will enroll children and pregnant women, although these groups will be brought on in a stepwise manner after DSMB safety reviews.

Approximately 40 sites in the United States will be utilized for this protocol. One hundred eligible participants will be randomized in a 1:1 ratio to receive either 2 units (or pediatric equivalent) of H1N1 plasma on Study Day 0 in addition to standard care or standard care alone (50 participants receiving standard care alone; 50 participants receiving H1N1 plasma).

Participants will be assessed on Study Day 0 (pre-dose); 30 minutes after infusion with each of the 2 units of plasma; and 1, 2, 4, 7, 14, and 28 days after infusion. All participants will undergo a series of efficacy, safety, and pharmacokinetic assessments during the study, including physical exams and collection of medical histories. Blood samples and throat and nose swabs will be collected at each time point.