Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study

IRC002 Study Team

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)500-511
Number of pages12
JournalThe Lancet Respiratory Medicine
Volume5
Issue number6
DOIs
StatePublished - Jun 1 2017

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Human Influenza
Therapeutics
Standard of Care
National Institute of Allergy and Infectious Diseases (U.S.)
Tachypnea
Hospitalized Child
Antibodies
Adult Respiratory Distress Syndrome
National Institutes of Health (U.S.)
Hemagglutination
Respiratory Rate
Artificial Respiration
Pregnant Women
Stroke
Air
Pediatrics
Oxygen
Morbidity
Safety
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Immune plasma for the treatment of severe influenza : an open-label, multicentre, phase 2 randomised study. / IRC002 Study Team.

In: The Lancet Respiratory Medicine, Vol. 5, No. 6, 01.06.2017, p. 500-511.

Research output: Contribution to journalArticle

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title = "Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study",
abstract = "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.",
author = "{IRC002 Study Team} and Beigel, {John H.} and Pablo Tebas and Elie-Turenne, {Marie Carmelle} and Ednan Bajwa and Bell, {Todd E.} and Cairns, {Charles B.} and Shmuel Shoham and Deville, {Jaime G.} and Eric Feucht and Judith Feinberg and Thomas Luke and Kanakatte Raviprakash and Janine Danko and Dorothy O'Neil and Metcalf, {Julia A.} and Karen King and Burgess, {Timothy H.} and Evgenia Aga and Lane, {H. Clifford} and Hughes, {Michael D.} and Davey, {Richard T.} and Pablo Tebas and Joseph Quinn and Yan Jiang and Elie-Turenne, {Marie Carmelle} and Robyn Hoelle and Nicole Iovine and Wills, {Robert Shawn} and Socorro Pata and Monique Huggins and Belinda Manukian and Ednan Bajwa and Carrie Holland and Kelsey Brait and Taylor Hunt and Christopher Stowell and Amy Slater and Bell, {Todd E.} and Mary Townsends and Cairns, {Charles B.} and Quackenbush, {Eugenia B.} and Park, {Yara A.} and Jordan, {Paul Gaither} and Cherie Blanchet and Kevin Chronowski and Kathleen Alvarez and Shmuel Shoham and Darin Ostrander and Terry Woessner and Ognjen Gajic",
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TY - JOUR

T1 - Immune plasma for the treatment of severe influenza

T2 - an open-label, multicentre, phase 2 randomised study

AU - IRC002 Study Team

AU - Beigel, John H.

AU - Tebas, Pablo

AU - Elie-Turenne, Marie Carmelle

AU - Bajwa, Ednan

AU - Bell, Todd E.

AU - Cairns, Charles B.

AU - Shoham, Shmuel

AU - Deville, Jaime G.

AU - Feucht, Eric

AU - Feinberg, Judith

AU - Luke, Thomas

AU - Raviprakash, Kanakatte

AU - Danko, Janine

AU - O'Neil, Dorothy

AU - Metcalf, Julia A.

AU - King, Karen

AU - Burgess, Timothy H.

AU - Aga, Evgenia

AU - Lane, H. Clifford

AU - Hughes, Michael D.

AU - Davey, Richard T.

AU - Tebas, Pablo

AU - Quinn, Joseph

AU - Jiang, Yan

AU - Elie-Turenne, Marie Carmelle

AU - Hoelle, Robyn

AU - Iovine, Nicole

AU - Wills, Robert Shawn

AU - Pata, Socorro

AU - Huggins, Monique

AU - Manukian, Belinda

AU - Bajwa, Ednan

AU - Holland, Carrie

AU - Brait, Kelsey

AU - Hunt, Taylor

AU - Stowell, Christopher

AU - Slater, Amy

AU - Bell, Todd E.

AU - Townsends, Mary

AU - Cairns, Charles B.

AU - Quackenbush, Eugenia B.

AU - Park, Yara A.

AU - Jordan, Paul Gaither

AU - Blanchet, Cherie

AU - Chronowski, Kevin

AU - Alvarez, Kathleen

AU - Shoham, Shmuel

AU - Ostrander, Darin

AU - Woessner, Terry

AU - Gajic, Ognjen

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

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