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A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.
McElvaney, Oliver J; McEvoy, Natalie L; Boland, Fiona; McElvaney, Oisín F; Hogan, Grace; Donnelly, Karen; Friel, Oisín; Browne, Emmet; Fraughen, Daniel D; Murphy, Mark P; Clarke, Jennifer; Choileáin, Orna Ní; O'Connor, Eoin; McGuinness, Rory; Boylan, Maria; Kelly, Alan; Hayden, John C; Collins, Ann M; Cullen, Ailbhe; Hyland, Deirdre; Carroll, Tomás P; Geoghegan, Pierce; Laffey, John G; Hennessy, Martina; Martin-Loeches, Ignacio; McElvaney, Noel G; Curley, Gerard F.
  • McElvaney OJ; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • McEvoy NL; Beaumont Hospital, Dublin, Ireland.
  • Boland F; Department of Anaesthesia and Critical Care, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • McElvaney OF; Data Science Centre, Division of Biostatistics and Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Hogan G; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Donnelly K; Beaumont Hospital, Dublin, Ireland.
  • Friel O; Department of Anaesthesia and Critical Care, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Browne E; Beaumont Hospital, Dublin, Ireland.
  • Fraughen DD; Beaumont Hospital, Dublin, Ireland.
  • Murphy MP; Beaumont Hospital, Dublin, Ireland.
  • Clarke J; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Choileáin ON; Beaumont Hospital, Dublin, Ireland.
  • O'Connor E; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • McGuinness R; Beaumont Hospital, Dublin, Ireland.
  • Boylan M; Department of Anaesthesia and Critical Care, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Kelly A; Beaumont Hospital, Dublin, Ireland.
  • Hayden JC; Beaumont Hospital, Dublin, Ireland.
  • Collins AM; Beaumont Hospital, Dublin, Ireland.
  • Cullen A; Beaumont Hospital, Dublin, Ireland.
  • Hyland D; Beaumont Hospital, Dublin, Ireland.
  • Carroll TP; School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Geoghegan P; RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
  • Laffey JG; RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
  • Hennessy M; RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
  • Martin-Loeches I; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • McElvaney NG; Beaumont Hospital, Dublin, Ireland.
  • Curley GF; Department of Anaesthesia, Galway University Hospitals, SAOLTA University Health Group, Galway, Ireland.
Med (N Y) ; 3(4): 233-248.e6, 2022 04 08.
Article in English | MEDLINE | ID: covidwho-1882364
ABSTRACT

Background:

Patients with severe coronavirus disease 2019 (COVID-19) develop a febrile pro-inflammatory cytokinemia with accelerated progression to acute respiratory distress syndrome (ARDS). Here we report the results of a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of intravenous (IV) plasma-purified alpha-1 antitrypsin (AAT) for moderate to severe ARDS secondary to COVID-19 (EudraCT 2020-001391-15).

Methods:

Patients (n = 36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120 mg/kg), or AAT once followed by weekly placebo. The primary endpoint was the change in plasma interleukin (IL)-6 concentration at 1 week. In addition to assessing safety and tolerability, changes in plasma levels of IL-1ß, IL-8, IL-10, and soluble tumor necrosis factor receptor 1 (sTNFR1) and clinical outcomes were assessed as secondary endpoints.

Findings:

Treatment with IV AAT resulted in decreased inflammation and was safe and well tolerated. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group. This was in contrast to the placebo group, where IL-6 was increased. Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients receiving placebo. IV AAT did not definitively reduce levels of IL-1ß, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on ventilator was observed in AAT-treated patients.

Conclusions:

In patients with COVID-19 and moderate to severe ARDS, treatment with IV AAT was safe, feasible, and biochemically efficacious. The data support progression to a phase 3 trial and prompt further investigation of AAT as an anti-inflammatory therapeutic.

Funding:

ECSA-2020-009; Elaine Galwey Research Bursary.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Alpha 1-Antitrypsin Deficiency / COVID-19 Type of study: Controlled clinical trial / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: Med (N Y) Year: 2022 Document Type: Article Affiliation country: J.medj.2022.03.001

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Alpha 1-Antitrypsin Deficiency / COVID-19 Type of study: Controlled clinical trial / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: Med (N Y) Year: 2022 Document Type: Article Affiliation country: J.medj.2022.03.001