Efficacy and safety of SR1375 in hospitalized patients with pneumonia combined with underlying disease: a randomized, double-blind, placebo-parallel controlled trial

<bold>Background:</bold> Lp-PLA₂ is a phospholipase A₂ enzyme secreted primarily by monocyte-derived macrophages that binds predominantly to LDL in plasma. Hydrolysis of fatty acids by Lp-PLA₂ produces oxNEFA and LysoPC, which can mediate the release of inflammatory factors and are associated with the up-regulation of several markers of inflammation. This indicator is found to be elevated in patients with pneumonia. SR1375, acts as an inhibitor of Lp-PLA₂, and can modulate systemic inflammatory responses. <bold>Methods:</bold> In this randomized, double-blind, placebo-controlled clinical study, we recruited patients hospitalized patients with pneumonia combined with underlying disease. 36 patients was randomly assigned in a 1:1:1 ratio to the conventional treatment + SR1375 3mg group (3mg once daily in continuous 28 days), the conventional treatment + SR1375 10mg group (10mg once daily in continuous 28 days), the conventional treatment + placebo group, and the conventional treatment + placebo group. The primary end point was 7-category ordinal scale as of days 15 and 29. <bold>Result:</bold> On the basis of the widespread use of glucocorticoids in patients, SR1375 was still able to show modulation of key biomarkers, superior efficacy to conventional treatment (improvement in 7-category ordinal scale) and a favourable safety profile. Notably, patients in the 3 mg group had better efficacy than 10 mg when compared to the placebo group (−0.38 vs -0.06, <italic>p</italic>=0.05). In the subgroup of patients with concomitant interstitial pulmonary fibrosis, there was a trend towards a more pronounced therapeutic improvement in the 7-category ordinal scale (−0.44 vs -0.23, <italic>p</italic>=0.05).