Ivan F N Hung1, Kelvin K W To2, Cheuk-Kwong Lee3, Kar-Lung Lee4, Wing-Wa Yan5, Kenny Chan5, Wai-Ming Chan6, Chun-Wai Ngai6, Kin-Ip Law4, Fu-Loi Chow7, Raymond Liu8, Kang-Yiu Lai9, Candy C Y Lau2, Shao-Haei Liu10, Kwok-Hung Chan2, Che-Kit Lin3, Kwok-Yung Yuen11. 1. 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. 2. Carol Yu Center for Infection and Division of Infectious Diseases, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. 3. Hong Kong Red Cross Blood Transfusion Service, Hong Kong. 4. Department of Intensive Care Unit, United Christian Hospital, Hong Kong. 5. Department of Intensive Care Unit, Pamela Youde Nethersole Eastern Hospital, Hong Kong. 6. Department of Anaesthesia and Intensive Care Unit, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. 7. Department of Medicine and Geriatrics, Intensive Care Unit, Caritas Medical Centre, Hong Kong. 8. Department of Medicine, Ruttonjee Hospital and Tang Shiu Kin Hospitals, Hong Kong. 9. Department of Intensive Care Medicine, Queen Elizabeth Hospital, Hong Kong. 10. Department of Infection, Emergency and Contingency, Hospital Authority of Hong Kong Special Administrative Region, China. 11. 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.
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. TRIAL REGISTRY: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.
RCT Entities:
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. TRIAL REGISTRY: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.
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