Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study
2017; Elsevier BV; Volume: 5; Issue: 6 Linguagem: Inglês
10.1016/s2213-2600(17)30174-1
ISSN2213-2619
AutoresJohn H. Beigel, Pablo Tebas, Marie‐Carmelle Elie‐Turenne, Ednan K. Bajwa, Todd E Bell, Charles B. Cairns, Shmuel Shoham, Jaime Deville, Eric C. Feucht, Judith Feinberg, Thomas Luke, Kanakatte Raviprakash, Janine R. Danko, Dorothy O’Neil, Julia A. Metcalf, Karen E. King, Timothy Burgess, Evgenia Aga, H. Clifford Lane, Michael D. Hughes, Richard T. Davey, Pablo Tebas, Joseph Quinn, Yan Jiang, Marie‐Carmelle Elie‐Turenne, Robyn Hoelle, Nicole M. Iovine, Robert Shawn Wills, Socorro Pata, Monique Huggins, Belinda Manukian, Ednan K. Bajwa, Carrie A. Holland, Kelsey Brait, Taylor Hunt, Christopher P. Stowell, Amy Slater, Todd E Bell, Mary Townsends, Charles B. Cairns, Eugenia Quackenbush, Yara A. Park, Paul Gaither Jordan, C. Blanchet, Kevin Chronowski, K. Alvarez, Shmuel Shoham, Darin Ostrander, Terry Woessner, Sandra K. Thoman, Jaime Deville, Yi-Chan Lin, Alyssa Ziman, Kavita Shankar, Eric C. Feucht, Tom Blok, D. H. Batts, Bob Beck, Gail Massey, Carol Bradley, Judith Feinberg, Patricia M. Carey, Jenifer Baer, Eva Moore Whitehead, Sharon Kohrs, Robert Giulitto, Christina Schofield, Mary Fairchok, Susan Chambers, Cindy M. Baker, RN, Michelle Parker, Marta Harshbarger, M. Hong Nguyen, Mary Ellen Carey, Julie Paronish, Frank Frank Cornell, Jim Cramer, Diana L. Pakstis, Michael G. Ison, Richard G. Wunderink, Marshall J. Glesby, Kirsis Ham, Valery Hughes, Melissa M. Cushing, Cheryl Goss, Joanne Grenade, Pauline K. Park, Lena M. Napolitano, Krishnan Raghavendran, Robert C. Hyzy, Robertson D. Davenport, Kristin Brierley, Theresa Downs, Michelle N. Gong, Joan Uehlinger, Michael Lin, Janice M. Fritsche, Tondria Green, Bruce McLeod, Deena Patel, Mary Bavaro, Robert Deiss, Carolyn Brandt, Stephanie Cammarata, Allan Kremp, Monique Hollis-Perry, Tahaniyat Lalani, Susan Banks, Jacqueline L. Johnson, Jason D. Maguire, Janet McNiff, Leslie E Rigg, Anuradha Ganesan, Irma Barahona, Janine R. Danko, Steven K. Spencer, David R. Stagliano, Timothy Burgess, Daniel Talmor, Monique Mohammed, Valerie Banner‐Goodspeed, Robert A. Salata, Robert W. Finberg, Jennifer Wang, Karen Longtine, Jaclyn Longtine, Mellissa O'Neil, Philippe R. Bauer, Ognjen Gajic, Suanne M Weist, Jonathan Sevransky, Mona Brown, John D. Roback, John Oropello, Bridget Twohig, Jeffrey S. Jhang, Rahgu Seethala, Wilbur H. Chen, Magali J. Fontaine, Kapil Saharia, Jennifer Husson, Roberta L. DeBiasi, Jurran L Wilson, V. R. Criss, Jocelyn Voell, Susan F. Leitman, James Wade Atkins, Hemaxi Patel, Traci Paige, Cathy Cantilena, Donald L. Siegel, Faye DeMuth, Craig H. Fletcher, Joseph Pelletier, Hassan Alnuaimat, Michelle Pourde,
Tópico(s)Diabetes and associated disorders
ResumoBackgroundInfluenza 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.MethodsIn 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.FindingsBetween 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).InterpretationAlthough 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.FundingNational Institute of Allergy and Infectious Diseases, US National Institutes of Health.
Referência(s)