title: Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection.
abstract: BACKGROUND
  Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking.
  
  
  METHODS
  This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared.
  
  
  RESULTS
  Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04).
  
  
  CONCLUSIONS
  Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality.
  
  
  BACKGROUND
  ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.
authors: Carol Yu Center for Infection and Division of Infectious Diseases, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors: Ivan F N
authors: IFN
authors: Hung
authors: Carol Yu Center for Infection and Division of Infectious Diseases, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors: Kelvin K W
authors: KKW
authors: To
authors: Hong Kong Red Cross Blood Transfusion Service, Hong Kong.
authors: Cheuk-Kwong
authors: CK
authors: Lee
authors: Department of Intensive Care Unit, United Christian Hospital, Hong Kong.
authors: Kar-Lung
authors: KL
authors: Lee
authors: Department of Intensive Care Unit, Pamela Youde Nethersole Eastern Hospital, Hong Kong.
authors: Wing-Wa
authors: WW
authors: Yan
authors: Department of Intensive Care Unit, Pamela Youde Nethersole Eastern Hospital, Hong Kong.
authors: Kenny
authors: K
authors: Chan
authors: Department of Anaesthesia and Intensive Care Unit, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors: Wai-Ming
authors: WM
authors: Chan
authors: Department of Anaesthesia and Intensive Care Unit, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors: Chun-Wai
authors: CW
authors: Ngai
authors: Department of Intensive Care Unit, United Christian Hospital, Hong Kong.
authors: Kin-Ip
authors: KI
authors: Law
authors: Department of Medicine and Geriatrics, Intensive Care Unit, Caritas Medical Centre, Hong Kong.
authors: Fu-Loi
authors: FL
authors: Chow
authors: Department of Medicine, Ruttonjee Hospital and Tang Shiu Kin Hospitals, Hong Kong.
authors: Raymond
authors: R
authors: Liu
authors: Department of Intensive Care Medicine, Queen Elizabeth Hospital, Hong Kong.
authors: Kang-Yiu
authors: KY
authors: Lai
authors: Carol Yu Center for Infection and Division of Infectious Diseases, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors: Candy C Y
authors: CCY
authors: Lau
authors: Department of Infection, Emergency and Contingency, Hospital Authority of Hong Kong Special Administrative Region, China.
authors: Shao-Haei
authors: SH
authors: Liu
authors: Carol Yu Center for Infection and Division of Infectious Diseases, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors: Kwok-Hung
authors: KH
authors: Chan
authors: Hong Kong Red Cross Blood Transfusion Service, Hong Kong.
authors: Che-Kit
authors: CK
authors: Lin
authors: Carol Yu Center for Infection and Division of Infectious Diseases, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. Electronic address: kyyuen@hkucc.hku.hk.
authors: Kwok-Yung
authors: KY
authors: Yuen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016756:Immunoglobulins, Intravenous