Alpha-1 antitrypsin for ARDS secondary to severe COVID-19

The results of a randomised, phase 2 trial of intravenous, plasma-purified alpha-1 antitrypsin (AAT) for moderate-to-severe acute respiratory distress syndrome (ARDS) secondary to COVID-19 indicated that the treatment is safe and biochemically effective.

A phase 2, randomised, multicentre, randomised, double-blind, placebo-controlled study (EudraCT 2020-001391-15) investigated the use of anti-inflammatory protein AAT purified from the blood of healthy donors as a therapeutic option for patients with severe COVID-19, particularly those who progressed to ARDS (n=36). Dr Oliver McElvaney (Royal College of Surgeons, Ireland) presented the results, which were also recently published in the journal Med [1,2].

The results showed that treatment with intravenous AAT resulted in decreased inflammation at 1 week, was safe and well tolerated, and did not interfere with patients’ ability to generate their own protective response to COVID-19. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group, as opposed to an IL-6 increase in the placebo group (see Figure). Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients in the placebo arm. AAT did not reduce levels of IL-1β, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on a ventilator was observed in AAT-treated patients.

Figure: Circulating IL-6 levels were significantly reduced in patients treated with AAT [1]



AAT, alpha-1 antitrypsin.

Based on these results, the researchers suggested that a phase 3 trial is warranted to assess the efficacy and safety of intravenous AAT for patients with ARDS secondary to severe COVID-19.

1. McElvaney O, et al. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Alpha-1 Antitrypsin for ARDS Secondary to Severe COVID-19. Session D94, ATS International Conference 2022, San Francisco, CA, USA, 13–18 May.
2. McElvaney OJ, et al. Med (N Y). 2022;3(4):233–248.

 

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Posted on 18 July 2022