1. Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study
- Author
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John H Beigel, Pablo Tebas, Marie-Carmelle Elie-Turenne, Ednan Bajwa, Todd E Bell, Charles B Cairns, Shmuel Shoham, Jaime G Deville, Eric Feucht, Judith Feinberg, Thomas Luke, Kanakatte Raviprakash, Janine Danko, Dorothy O'Neil, Julia A Metcalf, Karen King, Timothy H Burgess, Evgenia Aga, H Clifford Lane, Michael D Hughes, Richard T Davey, Joseph Quinn, Yan Jiang, Robyn Hoelle, Nicole Iovine, Robert Shawn Wills, Socorro Pata, Monique Huggins, Belinda Manukian, Carrie Holland, Kelsey Brait, Taylor Hunt, Christopher Stowell, Amy Slater, Mary Townsends, Eugenia B Quackenbush, Yara A Park, Paul Gaither Jordan, Cherie Blanchet, Kevin Chronowski, Kathleen Alvarez, Darin Ostrander, Terry Woessner, Sandra Thoman, James Lin, Alyssa Ziman, Kavita Shankar, Tom Blok, Don Batts, Bob Beck, Gail Massey, Carol Bradley, Patricia Carey, Jenifer Baer, Eva Moore Whitehead, Sharon Kohrs, Robert Giulitto, Christina Schofield, Mary Fairchok, Susan Chambers, Cindy Baker, null RN, Michelle Parker, Marta Harshbarger, M Hong Nguyen, Mary Ellen Carey, Julie Paronish, Frank Cornell, Jim Cramer, Diana Lynn Pakstis, Michael G Ison, Richard Wunderink, Marshall Glesby, Kirsis Ham, Valery Hughes, Melissa Cushing, Cheryl Goss, Joanne Grenade, Pauline K Park, Lena M Napolitano, Krishnan Raghavendran, Robert C Hyzy, Robertson Davenport, Kristin Brierley, Theresa Downs, Michelle Ng Gong, Joan Uehlinger, Michael Lin, Janice Fritsche, Tondria Green, Bruce McLeod, Deena Patel, Mary F Bavaro, Robert Deiss, Carolyn Brandt, Stephanie Cammarata, Allan Kremp, Karine Hollis-Perry, Tahaniyat Lalani, Susan Banks, Jacqueline Johnson, Jason Maguire, Janet McNiff, Leslie E Rigg, Anuradha Ganesan, Irma Barahona, Steven Spencer, David Stagliano, Timothy Burgess, Daniel Talmor, Monique Mohammed, Valerie Banner-Goodspeed, Robert Salata, Robert Finberg, Jennifer Wang, Karen Longtine, Jaclyn Longtine, Mellissa O'Neil, Philippe R Bauer, Ognjen Gajic, Suanne M Weist, Jonathan Sevransky, Mona Brown, John Roback, John Oropello, Bridget Twohig, Jeffrey Jhang, Rahgu Seethala, Wilbur H Chen, Magali Fontaine, Kapil Saharia, Jennifer Husson, Roberta DeBiasi, Jurran L Wilson, Valli Ree Criss, Jocelyn Voell, Susan Leitman, James Wade Atkins, Hemaxi Patel, Traci Paige, Cathy Cantilena, Donald Siegel, Faye DeMuth, Craig H Fletcher, J Peter R Pelletier, Hassan Alnuaimat, and Michelle Pourde
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Mechanical ventilation ,Pediatrics ,medicine.medical_specialty ,Respiratory rate ,business.industry ,medicine.medical_treatment ,Hazard ratio ,medicine.disease ,law.invention ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Randomized controlled trial ,law ,Clinical endpoint ,Medicine ,030212 general & internal medicine ,business ,Adverse effect ,Stroke - Abstract
Summary Background Influenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports suggest that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza. Methods In this randomised, open-label, multicentre, phase 2 trial, 29 academic medical centres in the USA assessed the safety and efficacy of anti-influenza plasma with haemagglutination inhibition antibody titres of 1:80 or more to the infecting strain. Hospitalised children and adults (including pregnant women) with severe influenza A or B (defined as the presence of hypoxia or tachypnoea) were randomly assigned to receive either two units (or paediatric equivalent) of anti-influenza plasma plus standard care, versus standard care alone, and were followed up for 28 days. The primary endpoint was time to normalisation of patients' respiratory status (respiratory rate of ≤20 breaths per min for adults or age-defined thresholds of 20–38 breaths per min for children) and a room air oxygen saturation of 93% or more. This study is registered with ClinicalTrials.gov, number NCT01052480. Findings Between Jan 13, 2011, and March 2, 2015, 113 participants were screened for eligibility and 98 were randomly assigned from 20 out of 29 participating sites. Of the participants with confirmed influenza (by PCR), 28 (67%) of 42 in the plasma plus standard care group normalised their respiratory status by day 28 compared with 24 (53%) of 45 participants on standard care alone (p=0·069). The hazard ratio (HR) comparing plasma plus standard care with standard care alone was 1·71 (95% CI 0·96–3·06). Six participants died, one (2%) from the plasma plus standard care group and five (10%) from the standard care group (HR 0·19 [95% CI 0·02–1·65], p=0·093). Participants in the plasma plus standard care group had non-significant reductions in days in hospital (median 6 days [IQR 4–16] vs 11 days [5–25], p=0·13) and days on mechanical ventilation (median 0 days [IQR 0–6] vs 3 days [0–14], p=0·14). Fewer plasma plus standard care participants had serious adverse events compared with standard care alone recipients (nine [20%] of 46 vs 20 [38%] of 52, p=0·041), the most frequent of which were acute respiratory distress syndrome (one [2%] vs two [4%] patients) and stroke (one [2%] vs two [4%] patients). Interpretation Although there was no significant effect of plasma treatment on the primary endpoint, the treatment seemed safe and well tolerated. A phase 3 randomised trial is now underway to further assess this intervention. Funding National Institute of Allergy and Infectious Diseases, US National Institutes of Health.
- Published
- 2017
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