Short-term inhalation of sargramostim with concomitant high-dose steroids does not hasten recovery in moderate COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial
Shigeki Shimasaki, Tomohisa Baba, Takashi Ogura, Keiichi Akasaka, Hidekazu Matsushima, Shinyu Izumi, Jin Takasaki, Kenji Tsushima, Toru Kinouchi, Yoshiko Kichikawa, Maiko Awashima, Takehiro Izumo, Nobuyasu Awano, Naoki Nishimura, Ryushi Tazawa, Ayako Mikami, Nobutaka Kitamura, Haruyuki Ishii, Yasuyuki Kurihara, Masaki Taniguchi, Satoko Aikawa, Mami Okada, Yusuke Morita, Yuko Ishikawa, Akira Ohinata, Koh Nakata
Infectious Diseases, doi:10.1080/23744235.2023.2254380
Background: Granulocyte-macrophage colony stimulating factor (GM-CSF) inhalation may alleviate pulmonary inflammation caused by viral pneumonia. To investigate this, we evaluated its efficacy on COVID-19 pneumonia. Methods: This double-blind, randomised, placebo-controlled study (ClinicalTrials.gov: NCT04642950) evaluated patients in the first half of 2021 at seven Japanese hospitals. Hospitalised patients with COVID-19 pneumonia with moderate hypoxaemia inhaled sargramostim or placebo for 5 days. The primary endpoint was days to achieve a ! 2-category improvement from baseline on a modified 7-category ordinal scale. Secondary endpoints included degree of oxygenation, defined by amount of oxygen supply, and serum CCL17 level. Results: Seventy-five patients were randomly assigned in a 2:1 ratio to receive sargramostim or placebo, of which 47 and 23 were analysed, respectively. No difference was observed between groups regarding the primary endpoint (8.0 and 7.0 days for sargramostim and placebo, respectively) or in the secondary endpoints, except for CCL17. A post hoc sub-analysis indicated that endpoint assessments were influenced by concomitant corticosteroid therapy. When the cumulative corticosteroid dose was 500 mg during Days 1-5, recovery and oxygenation were faster in the sargramostim group than for placebo. Bolus dose corticosteroids were associated with temporarily impaired oxygenation and delayed clinical recovery. The increase in serum CCL17, a candidate prognostic factor, reflected improvement with sargramostim inhalation. The number of adverse events was similar between groups. Two serious adverse events were observed in the sargramostim group without causal relation.
Authors' contribution lying data reported in this manuscript. All authors had full The study was also sponsored by Nobelpharma, which was involved in the collection, analysis, and interpretation of the data; in the writing of the report, and in the decision to submit the paper for publication. The authors thank Dr Hannah Read, of Edanz (www.edanz.com) for medical writing assistance, which was funded by Nobelpharma, in accordance with Good Publication Practice guidelines (https://www.ismpp.org/gpp-2022). The authors also thank Dr Steven Holland and Dr Kiyoko Akagawa for critical review of this manuscript.
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